Feasibility and Outcomes of Allogeneic Hematopoietic Cell Transplantation (HCT) Compared to Conventional Therapy for Older and Medically Infirm Patients Diagnosed With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes: A Prospective Observational Study
Conditions: Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
Sponsor: Fred Hutchinson Cancer Center

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F R E D H U T C HI N S O N C A N C E R R E S E A R C H C E N T E R  
U NI V E R SI T Y O F W A S HI N G T O N S C H O O L O F M E DI CI N E  
C HI L D R E N’ S H O S PI T A L A N D R E GI O N A L M E DI C A L C E N T E R  
  
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1. Fe asi bilit y a n d O utc o mes of All o ge neic He m at o p oietic Cell Tr a ns pl a nt ati o n ( H C T) C o m p are d t o 
C o n ve nti o n al T her a p y  f or Ol der a n d Me dic all y I nfir m P atie nts Di a g n ose d wit h Ac ute M yel oi d Le u ke mi a 
or Hi g h- Ris k M yel o d ys pl astic S y n dr o mes: A Pr os pecti ve O bser v ati o n al St u d y  
  
Pri nci p al I n vesti g at or: 
M o ha me d L. S orr or, M D, M Sc Ass ociate  Me m ber, F H C R C; Ass ociate  Pr ofess or of Me dici n e, U W ( 6 6 7- 6 2 9 8) 
C o -I n vesti g at ors: 
Eli h u H. Este y, M D    
  
Me m ber, F H C R C; Pr ofess or of Me dici ne, U W   
  
( 2 8 8- 7 1 7 6)  
Ste p ha nie Lee, M D, M P H   
 
Me m ber, F H C R C; Pr ofess or of Me dici ne, U W    
  
( 6 6 7- 6 1 9 0) 
Pa mela Bec ker, M D, P h D   
 
Ass ociate Pr ofess or of M e dici ne, U W   
  
  
( 6 1 6- 1 5 8 6) 
Rai ner St or b , M D  
  
  
Me m ber, F H C R C; Pr ofess or of Me d ici ne, U W  
  
( 6 6 7- 4 4 0 7) 
R ola n d Walter, M D, P h D  
 
Assista nt Me m ber, F H C R C; Assista nt Pr of of Me d, U W  
( 6 6 7- 3 5 9 9) 
H. J oac hi m Dee g, M D  
  
Me m ber, F H C R C, Pr ofess or of Me dici ne, U W   
  
( 6 6 7- 5 9 8 5) 
Pa ul He n drie, M D, P h D  
 
Ass ociate Pr ofess or of M e dici ne, U W   
  
  
( 2 8 8- 6 3 6 6) 
Bre n d a M. Sa n d maier, M D     
Me m ber, F H C R C; Pr ofess or of Me dici ne, U W   
  
( 6 6 7- 4 9 6 1) 
Fre d eric k R. A p p el ba u m, M D 
Me m ber, F H C R C;  Pr ofess or of Me dici ne, U W  
   
( 6 6 7- 4 4 1 2)  
J e n nifer N yla n d, P h D   
 
Staff Scie ntist , F H C R C  
  
  
  
  
( 6 6 7- 1 8 4 5) 
 
St u d y C o or di n at or s: 
Rac helle M o ore , B S  
  
  
( 2 0 6) 6 6 7- 6 1 2 2; Pa ger ( 2 0 6) 3 1 4- 2 5 9 5 
S o p hie Fle uret , B S  
  
  
( 2 0 6) 6 6 7- 7 9 4 9; Pa ger ( 2 0 6) 3 1 4- 3 1 8 0 
Pr oject M a n a ger:  
S h yl o War d y n , M S  
  
  
( 2 0 5) 6 6 7- 7 2 6 3 
Bi ost atistici a n:   
 
Barr y St orer, P h D  
  
  
Me m ber, F H C R C; Pr ofess or of  Bi ostatistics, U W     
( 6 6 7- 6 1 5 1) 
 
A d diti o n al Perf or m a nce Sites   
  
I n vesti g at ors    
 
E mer ge nc y P h o ne N u m bers  
Sta nf or d Sc h o ol of Me di ci ne    
  
Br u n o Me d eir os, M D    
( 6 5 0) 4 9 8- 5 0 0 0 
N ort h wester n U ni versit y   
  
  
Ke hi n de A de k ol a, M D  
( 3 1 2) 6 9 5- 6 1 8 0 
Cle vela n d Cli nic   
  
  
  
Aar o n G er ds, M D  
  
( 2 1 6) 4 4 5- 9 3 5 3 
U ni versit y of Uta h   
  
  
  
Pa ul S ha mi, M D  
  
( 8 0 1) 5 8 5- 5 1 3 6 
U ni versit y of Mar yla n d   
  
 
Maria Baer, M D   
  
( 4 1 0) 3 2 8- 8 7 0 8 
U ni versit y of Pe n ns yl v a nia    
 
Seli na L u ger, M D   
  
( 2 1 5) 6 1 4- 9 8 0 1 
Hac ke ns ac k U ni v ersit y Me d Ce nter     
J a mie K o pri v ni kar, M D  
( 5 5 1) 9 9 6- 3 9 2 5 
Was hi n gt o n U ni versit y i n St. L o uis   
Ta n ya Wil des, M D     
( 3 1 4) 3 6 2- 5 6 5 4 
D u ke U ni versit y Sc h o ol of Me dici ne  
Da vi d Rizzieri , M D    
( 9 1 9) 6 6 8- 1 0 4 0 
R os well Par k Ca ncer I nstit ute   
  
E u nice Wa n g, M D  
  
( 7 1 6) 8 4 5- 3 5 4 4 
Seattle Ca ncer Care Allia nce ( S C C A ) Net w or k Researc h Office   
  
( 2 0 6) 2 8 8- 7 2 3 2 
E mer ge nc y P h o ne N u m bers  
F H C R C   
  
  
  
  
  
  
  
  
( 2 0 6) 5 9 8- 8 9 0 2, Fa x ( 2 0 6) 5 9 8- 4 0 3 4 
 
 
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2. 0 I N T R O D U C TI O N  
 
T he nat ure of ac ut e m yel oi d le u ke mia ( A M L) c ha n ges wit h a ge. Differe nt c ut - offs ha v e bee n use d t o 
defi ne ol der A M L patie nts, t he m ost c o m m o n has bee n a ge ≥6 0 years. W he n c o m pare d wit h y o u n ger a d ults, 
A M L i n patie nts a ge d ≥6 0 years is m ore fre q u e ntl y prece d e d b y a m yel o d ys plastic s y n dr o me ( M D S), has 
u nfa v ora bl e c yt o ge n etics, m ore c o m m o nl y e x presses m ulti dr u g resista n ce, a n d he nce res p o n ds less well t o 
c he m ot hera p y [ 1- 3]. I n a d diti o n, ol der A M L patie nts are frailer wit h  p o or p erf or ma n ce stat us [ 3] a n d pr o ba bl y 
hi g her c o m or bi dit y b ur de n si milar t o ot her a gi n g p o p ulati o ns [ 4- 6]. As a res ult , treati n g a gi n g i n di vi d uals wit h 
A M L h as bee n a c h alle n ge wit h o nl y ≤1 0 % p atie nt s u r vi vi n g l o n ger t ha n 5 years. 
 
T he a d ve nt of n o n m yel o a blati ve or r e d uce d- i nte nsit y c o n diti o ni n g re gi me ns i n t he past deca d e  has 
br oa de ne d t h e eli gi bilit y criteria f or all o ge nei c H C T  t o i ncl u de ol der a n d me dicall y i nfir m  patie nts. Preli mi nar y 
data o n n o n m yel oa blati v e all o ge neic H C T a m o n g s mall n u m bers of ol der A M L p atie nts s h o ws 3 5- 5 0 % s ur vi val 
rates at 3- years, b etter t h a n e x pecte d wit h  c o n ve nti o nal c he m ot hera p y [ 7]. H o we ver, e xtra p olati o n of t hese 
res ults t o t he ge n eral ol der A M L p o p ulati o n is diffic ult, as t he y i ncl u de o nl y t h ose p atie nts w h o were e nr olle d 
o nt o t he H C T pr ot oc ols. Li ke wis e, patie nts wit h a relati vel y hi g h b ur de n of c o m or bi dities are li kel y e x cl u de d 
fr o m all o ge neic H C T, wit h t his selecti o n bias c o nf o u n di n g i nter pretati o n of H C T res ults. T he perce nta ges of 
patie nts n ot referre d f or H C T beca use of lac k of i ns ura nce c o v era ge, ra pi dl y pr o gressi n g dis ease, p o or ge neral 
c o n diti o n, or p h ysicia n prefere nce are u n k n o w n.  
 
O ur pri mar y g o al here is t o i n vesti gate h o w ofte n ol der a n d me dicall y i nfir m patie nts , w h o are 
dia g n ose d wit h A M L or hi g h-ris k m yel o d ys plasti c s y n dr o mes ( M D S) a n d treate d wit h i n d ucti o n t hera p y, 
u n der g o all o ge nei c H C T  i n f o ur c olla b orati n g i nstit uti o ns. We will i n vesti gate differe nt fact ors t hat mi g ht affect 
t he rate of ref err al t o all o ge n eic H C T. T hes e rat es a n d reas o ns will be c o m pared t o t h ose i n y o u n ger a nd 
healt hier A M L/ M D S pati e nts. U n dersta n di n g selecti o n bias, we will f oll o w t he pr os pecti vel y e nr olle d patie nts 
f or a d diti o nal 2 4 m o nt hs a n d descri b e t heir o utc o mes c o m pari n g all o ge n eic H C T vers us c o n v e nti o nal t hera p y. 
 
3. B A C K G R O U N D  
3. 1 A M L i n ol der p atie nts:  
 
I n 2 0 0 6, a n esti mate d 1 3, 4 1 0 i n di vi d uals ( 7, 0 6 0 me n, 6, 3 5 0 w o me n) i n t he U nite d States ( U S) 
de vel o pe d A M L, w hile a n ot her 8, 9 9 0 i n di vi d uals ( 5, 0 2 0 me n, 3, 9 7 0 w o me n) die d fr o m t he disease [ 8] . A M L is 
a disease of t h e el derl y wit h a me dia n a ge at dia g n osis of 6 8 years. W hile t he a vera ge a n n ual i nci de n c e of A M L 
is a p pr o xi matel y 3. 4 3 p er 1 0 0, 0 0 0, it i ncreases pr o gressi vel y wit h a ge, t o a pea k of 5 5. 1 p er 1 0 0, 0 0 0 at a ge ≥6 5 
[ 9]. M ore o ver, de m o gr a p hic c ha n ges i n t he U S p o p ulati o n s u g gest t hat pati e nts ≥6 5 years ol d will c o nstit ute 
2 0 % at 2 0 3 0 a n d t he y will e x perie nce a 7 7 % i n crease i n dia g n oses of A M L bet wee n years 2 0 1 0 a n d 2 0 3 0 [ 1 0]. 
T h us, esta blis hi n g n o vel criteria f or o utc o me pre dicti o n a m o n g ol der A M L patie nts has bec o me a n i m p orta nt 
f ut ure g oal. 
 
Researc h o n a nti -le u ke mi a t hera p y a n d i m pr ove me nts i n s u p p orti ve care i n t he past t hree d eca des has 
res ulte d i n relati ve i m pr o ve me nt i n t he o utc o mes of A M L wit h 5-year s ur vi v al of a b o ut 2 0 %.[ 9] . Ne vert heless, 
t he pr o gress i n treati n g ol der patie nts wit h A M L h as bee n ver y li mite d [ 1 1], wit h 5 - year s ur vi v al rat es of o nl y 
5. 3 % a n d 1. 6 % f or patie nts a ge d 6 5- 7 4 a n d ≥7 5 ye ars c o m pare d t o 4 5. 5 % f or t h ose < 4 5 years, res pecti vel y [ 9]. 
T here are ma n y pres u me d reas o ns f or t he p o or o utc o mes a m o n g ol d er A M L patie nts. W he n c o m p are d wit h 
y o u n ger a d ults, A M L i n patie nts a ge d ≥6 0 years is t h o u g ht t o be m ore a g gressi ve gi ve n m ore fre q u e nt 
a ntece d e nt bl o o d d ys crasias, m ore fr e q ue nt u nfa v ora ble c y t o ge n etic a b n or malities, m ore c o m m o n e x pressi o n of 
m ulti -dr u g resista n ce pr otei ns s uc h a s P- gl yc o pr ot ei n, a n d he nce p o or res p o nse t o c he m ot hera p y.[ 1- 3] 
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O n t he ot her ha n d, ol der A M L p atie nts mi g ht e x perie nce rel ati vel y hi g h da y- 3 0 N R M ( u p t o 2 5 %[ 1 2] 
c o m pare d t o 0- 1 0 % a m o n g y o u n ger patie nts) [ 3, 1 2] . T hese res ults ha ve li mite d t he accr u al of ol der A M L 
pati e nts t o cli nical trials e x pl ori n g n o vel or hi g her i nte nsit y treat me nts, res ulti n g i n s u b -o pti mal t hera p y of t heir 
le u ke mia. W het her a ge p er se or its i nteracti o n wit h ot her ris k fact ors is res p o nsi ble f or t he hi g h N R M is n ot 
reall y k n o w n. F or e x a m ple, p o orer p erf or m a nce st at us was ass ociat e d wit h i ncreas e d m ortalit y a m o n g ol der 
patie nts i n t he S o ut h west O nc ol o g y Gr o u p ( S W O G) retr os p ecti ve st u d y [ 3] . Bi ol o gical a gi n g is h y p ot heticall y 
c o m p ose d of t hree par a m eters: a ge, p h ysical f u ncti o n, a n d or ga n c o m or bi dities. I n d ee d, a m o n g 4 2 7 ca ncer 
patie nts, a ge, f u n cti o nal i m pair me nt, a n d c o m or bi dities were f o u n d t o i n de pe n de ntl y pre dict patie nt s ur vi val 
re gar dl ess of t he t y pe of ca ncer [ 1 3]. T o date, t he r ole of c o m or bi dities i n t he decisi o n-ma ki n g f or tr eat me nt of 
ol der A M L patie nts has n ot bee n caref ull y a n al yze d.  
  
3. 2 C o m or bi dities a n d C a ncer :  
 
C o m or bi dities are li kel y t he mai n fact or b e hi n d m or bi dit y a n d m ortalit y aft er treat me nt of ol der p atie nts 
wit h ca ncer. T his is i n partic ular si nce First; i n a ‘t y pical' geriatri c series, i n di vi d uals, w h o are 6 5 years of a ge 
a n d ol der s uff er o n a ver a ge fr o m t hree differe nt diseases [ 4]. Sec o n dl y, pre vi o us researc h has d e m o nstrate d t ha t 
se verit y of a gi ve n c o m or bi dit y c o ul d si g nifi ca ntl y alter t he t y pe of i nitial a nti-ca ncer treat me nt. F or e x a m ple, 
Va n S pr o nse n et al d eter mi ne d t hat 5 0 % a n d 1 5 % less c he m ot hera p y were a d mi nistere d t o ol der patie nts wit h 
H o d g ki n a n d n o n- H o d g ki n l y m p h o m as a n d c o m or bi dities, res pecti vel y, w h e n c o m pare d t o t h ose wit h o ut 
c o m or bi dities [ 1 4]. I n a d diti o n, a ge a n d c o m or bi dities ha ve bee n i de ntifie d as pr o g n ostic fact ors f or l o n g-ter m 
Q O L of ca ncer patie nts [ 1 5- 1 9]. C o m or bi dit y has a n i n de pe n de nt i m pact fr o m f u ncti o nal stat us a n d, t heref ore, 
c o ul d pr o vi de a d diti o nal pr o g n ostic i nf or mati o n i n ol der ca n cer p atie nts [ 2 0]. 
  
Ne vert hel ess, patie nts wit h c o m or bi dities ha ve oft e n bee n e x cl u de d fr o m cli nical trials, a n d t here h as 
bee n little i nf or mati o n o n h o w t o tra nslate res ults fr o m c o o perati ve st u dies t o gi ve n p atie nts wit h c o m or bi dities. 
I n p artic ular, i nf or mati o n o n t he pre vale n ce of c o m or bi dities a m o n g A M L patie nts at dia g n osis, partic ularl y 
t h ose ≥6 0 years of a ge is lac ki n g fr o m t he literat ure. Li k e wise, t he i m pact of differe nt c o m or bi dities o n 
treat me nt c o m plia nce, t o xicit y, eli gi bilit y f or H C T, a n d e ve nt ual o utc o m es of A M L p atie nts is u n k n o w n. 
 
Certai n bi o mar kers h a ve a trac k -rec or d of b ei n g ass ociate d wit h s pecific or ga n c o m or bi dit y a m o n g t he 
ge n eral p o p ulati o n of p atie nts a n d ha ve t he p ote nti al t o i nfl ue nce treat me nt- relate d m or bi dit y a n d m ortalit y.  I n 
partic ular, ser u m al b u mi n has bee n see n t o i n vers el y c orrelate wit h a ge, s m o ki n g, o besit y, a n d h y p erte nsi o n.  It 
ser ves as a mar ker of i nfl a m mat or y st at us a n d pre dicts car di o vasc ul ar m ort alit y [ 2 1].  Hi g h ser u m ferriti n is a n 
ac ute p has e reacta nt a n d a s u g geste d meas ure of ir o n o verl oa d, w hic h h as b ee n li n ke d t o p ost- H C T i nfecti o ns, 
he patic c o m plicati o ns, a n d p ul m o nar y c o m plicati o ns [ 2 2- 2 5].  C- reacti ve pr otei n ( C R P) is a n ac ute p hase 
react a nt t hat was f o u n d t o pre dict i nfecti o n, car di ac c o m plicati o ns, a n d m ortalit y [ 2 5, 2 6]. Fi nall y, rece nt re p orts 
hi g hli g ht e d t he i m p orta n ce of vita mi n D le vels as a mar ker of vari o us a ut oi m m u ne diseases a n d a pre dict or of 
G V H D  [ 2 7]. We will caref ull y assess t he c o ntri b uti o n of t hese mar kers t o differe n t o utc o m es after di a g n osis of 
A M L. F urt her m ore, w e will e val uate t he p ossi ble a d diti o nal pr o g n ostic i m pacts of p ul m o nar y f u n cti o n tests 
( P F T), partic ularl y diff usi o n ca pacit y of car b o n m o n o xi de ( D Lc o) – after c orrecti o n of h e m o gl o bi n – a n d t he 
f orce d e x pirat or y v ol u me i n o ne sec o n d ( F E V 1) o n o utc o mes. 
 
3. 3 All o ge neic H C T f or ol der a n d me dic all y i nfir m A M L p atie nt :  
 
All o ge n eic H C T is a p ote ntiall y  c urati ve treat me nt f or ma n y patie nts wit h A M L. Hist oricall y, hi g h -
i nte nsit y c o n diti o ni n g re gi me ns ha ve bee n us e d wit h t he d ual ai ms of diseas e  era dicati o n a n d h ost 
i m m u n os u p pressi o n f or acce pta n ce of t h e 
 
all o grafts [ 2 8- 3 2]. M ore t ha n a deca de a g o, re d u ce d-i nte nsit y a n d 
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Fi g ur e 1 : A) A g e i nt er v a l s of 6 0-6 4, 6 5 -6 9, a n d ≥7 0 h a d n o i m p a ct o n N R M ( p 
= 0. 8 1) a m o n g r e ci pi e nt s of n o n m y el o a bl ati v e all o g e n ei c H C T, w hil e B)  H C T -CI 
s c or e s of 0, 1 -2, ≥3 w er e a s s o ci at e d wit h i n cr e a s e d N R M ( p  = 0. 0 0 2).  
A
P = 0. 8 1
Y e ar s aft er H C T
P er c e nt
P = 0. 0 0 2
B
A
P = 0. 8 1
Y e ar s aft er H C T
P er c e nt
P = 0. 0 0 2
B
tr ul y n o n m yel oa blati ve c o n diti o ni n g re gi me ns ha v e bee n i ntr o d uce d t o re d u ce t o xicities  a n d m ortalit y t hat ca n 
be ass ociate d wit h hi g h -i nte nsit y c o n diti o ni n g [ 3 3- 4 1]. T he ne w re gi me ns rel y i n part or e ntirel y o n graft-
vers us- le u ke mia effects f or t u m or era dicati o n. Ma n y p has e II tri als of RI C re gi me ns ha ve b ee n p u blis he d 
(re vie w e d i n[ 4 2]). T hese re gi me ns all o we d ol der p atie nts, t h ose w h o faile d prece di n g hi g h- d os e H C T, a n d t h ose 
wit h c o m or bi dities t o u n der g o all o ge nei c H C T.  
 
I n t w o re gistr y st u dies, i n vesti gat ors a nal yz e d o utc o mes of ol der patie nts di a g n os e d wit h A M L or 
m yel o d ys plastic s y n dr o mes ( M D S) a n d treate d wit h vari o us re d uce d- i nte nsit y re gi me ns f oll o w e d b y all o ge n eic 
H C T. I n a st u d y fr o m t he E ur o pea n Gr o u p of Bl o o d a n d Marr o w Tra ns pla nt ati o n [ 4 3], 4 4 9 patie nts > 6 0 years 
ol d ha d 4- year N R M of 3 9 % a n d O S of 2 7 %, w hi c h were n ot statisticall y si g nifica ntl y differe nt fr o m t h ose of 
y o u n ger patie nts. I n t he st u d y fr o m t he Ce nt er of I nter nati o nal Bl o o d a n d Marr o w Tra ns pla ntati o n Researc h 
( CI B M T R), [ 4 4] 3 7 6 patie nts > 6 0 years ha d 2- year N R M of 3 4 % a n d O S of 3 4 %. Neit her st u d y i ncl u de d 
i nf or mati o n o n patie nts’ me dical c o m or bi dities.  
 
 
T he Seattle C o ns orti u m i ncl u des 
2 3 c ol la b orati n g i nstit uti o ns w hic h ha ve 
e nr olle d 3 7 2  patie nts a ge d ≥6 0 years i nt o 
2 1 pr os pecti ve cli nical trials i n vesti gati n g 
all o ge n eic H C T after n o n m yel oa bl ati ve 
c o n diti o ni n g re gi me n of 2 G y t otal b o d y 
irra diati o n al o ne or wit h fl u dara bi ne 9 0 
m g/ m 2. O verall, t he c u m ulati ve i nci de nce 
of N R M a n d t he rat e of r ela pse were 2 7 % 
a n d 4 1 %, res p ecti vel y, lea di n g t o O S a n d 
D F S of 3 5 % a n d 3 2 %, res pecti vel y. 
Patie nts di d n ot statisticall y si g nifi ca ntl y 
differ i n t hese o ut c o mes w he n stratifie d b y a ge gr o u ps of 6 0- 6 5, 6 5- 7 0, or > 7 0 ye ars, w hile H C T -CI sc ores 
pre dicte d i ncreas e d N R M ( Fi g ure 1 ). At 5- years, 6 7 % of li vi n g patie nts were e ntirel y well w hile 3 3 % 
c o nti n ue d o n i m m u n os u p pressi ve me dicati o ns f or c hr o nic G V H D wit h a m e dia n perf or ma nce stat us of 9 0 % f or 
b ot h c o h orts. C o m or bi dities a n d disease ris ks f or rela pse, b ut n ot a ge, w ere t he mai n pre dict ors f or s ur vi val. I n a 
ris k-stratificati o n m o del, patie nts wit h l o w rela pse ris k a n d n o c o m or bi dities ha d 5- year O S of 6 9 %. We 
c o ncl u de d t hat wit h t he use of n o n m yel oa blati ve c o n diti o ni n g, a ge is n o l o n ger a barrier t o all o ge nei c H C T.[ 4 5] 
W hile t hese res ults s u g gest t olera nce of ol d er A M L patie nts t o re d uce d -i nte nsit y all o ge n eic H C T, it is 
n ot clear h o w t o tr a nslate t hese res ults t o t he g e neral p o p ulati o n of ol der patie nts dia g n ose d wit h A M L. Pr ot oc ol 
selecti o n criteri a mi g ht h a ve bee n selecti ve f or patie nts wit h mil der c o m or bi dit y b ur de n. O n t he ot h er ha n d, 
o nl y 1 2 % of p atie nts treate d wit h H C T bet wee n years 2 0 0 4- 2 0 0 8 were > 6 0 years ol d, [ 4 6] a n d o nl y 2 6 % o f 
A M L p atie nts w h o wer e see n i n c o ns ultati o n f or H C T e n de d u p recei vi n g it. [ 4 7] T his clearl y hi g hli g hts lac k of 
sta n dar d criteria f or referral of ol der A M L patie nts t o H C T a n d lac k of i nf or mati o n o n t he feasi bilit y of t his 
a p pr oac h, w hic h will be a d dresse d i n t he c urr e nt pr ot oc ol. 
  
3. 4 All o ge neic H C T vers us c o n ve nti o n al c he m ot her a p y f or ol der a n d me dic all y i nfir m p atie nts :  
 
 
T he r ole of re d uce d- i nte nsit y H C T i n treati n g ol der A M L patie nts will re mai n ver y li mite d as l o n g as 
patie nts a n d p h ysi cia ns are rel u cta nt t o c o nsi der t h e pr oce d ure. A pri or S W O G st u d y of t his a p pr oac h was 
cl ose d earl y b eca use of p o or accr ual, a n d a s u bse q ue nt st u d y of t he Ca n cer a n d Le u ke mia Gr o u p B ( C A L G B) 
has str u g gl e d as well (re vie we d i n [ 4 8]). B ot h st u dies were relati vel y s mall p hase II tri als wit h ver y m o dest 
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accr u al g oals f or a rel ati vel y c o m m o n disease. T h us, t here is a rel ucta nce t o refer patie nts f or all o ge n eic H C T. 
T his is li kel y d u e t o t w o reas o ns; first, patie nts a n d p h ys icia ns pr o ba bl y o v eresti mate t he be n efits of 
c o n ve nti o nal c he m ot hera p y a n d s ec o n dl y, ma n y n o n- tra ns pla nt p h ysicia ns li kel y o veresti mate the m or bi dit y of 
t he re d uce d-i nte nsit y H C T.   
 
T he feasi bilit y of all o ge n eic H C T was a d dresse d i n o ne relati vel y s mall st u d y fr o m t he M D A n ders o n 
Ca ncer Ce nter, w hic h i ncl u de d all u ntreate d A M L patie nts a ge d ≥5 0 years. Ni net y- ni n e ( 3 8 %) of a t otal of 2 5 9 
e nr olle d patie nts ac hie v e d C R. Of t he 9 9 patie nts, 5 3 were s ee n b y t he tra ns pla nt ser vice f or a c o ns ult. T he 
reas o ns f or n ot ref erri n g t he re mai ni n g 4 6 were u n clear i n al m ost half ( n = 2 1). A m o n g t h e 5 3 patie nts referre d t o 
H C T, s uita ble H L A- matc he d d o n ors were f o u n d f or 2 6 patie nts ( 2 1 si bli n gs, 5 u nrelate d) a n d 1 4 patie nts 
act uall y u n der w e nt H C T ( 1 3 fr o m si bli n g d o n ors). T he a ut h ors atte m pte d t o fi n d o ne or m ore c he m ot hera p y 
pair -mates f or  eac h patie nt w h o u n der we nt tr a ns pla ntati o n base d o n c yt o ge netic ris ks,  a ge, a n d lea d ti me bias. 
T here w as a > 9 9 % pr o b a bilit y t hat t he o utc o m e after RI C w as s u peri or t o t hat see n i n patie nts n ot tr a ns pla nte d. 
H o we ver, t he 1 4 patie nts w h o u n der w e nt tra ns pla ntati o n re prese nt o nl y 2 6 % of t h ose see n b y t h e tra ns pla nt 
ser vice, o nl y 1 4 % of all t h ose w h o ac hi e ve d C R, a n d o nl y 5 % of t h e ori gi nal 2 5 9 patie nts e ntere d i nt o t he st u d y. 
Clearl y, t his st u d y s uffer e d fr o m s mall sa m ple size a n d di d n ot e x a mi ne t he r ole of c o m or bi dities i n t he decisi o n 
n ot t o tra ns pla nt. We h o pe t o re me d y t his deficit h ere. F urt her, t h e H C T vers us  c he m ot hera p y c o m paris o n was 
u n der- p o w ere d, was li mite d t o a si n gle i nstit uti o n, a n d lac ke d d ata o n Q O L a n d t he patie nt’s decisi o n- ma ki n g 
fact ors. We will caref ull y a d dress all t hese p oi nts u n der t he c urre nt pr ot o c ol. 
 
Q O L is o ne of t he mai n c o ncer ns of ol d er s ur vi v ors of all o ge neic H C T, p artic ularl y gi v e n t he p ote nti al 
late c o m plicati o n s uc h as c hr o nic G V H D. A s mall st u d y atte m pte d t o c o m p are Q O L after m yel oa blati ve a n d 
re d uce d-i nte nsit y all o ge n eic H C T. All patie nts were y o u n ger t h a n 6 0 years, [ 4 9] w hic h ma kes t he st u d y of 
li mite d val ue t o t he vast maj orit y of p atie nts treat e d wit h re d uce d-i nte nsit y H C T. I n v esti gat ors o bser ve d si milar 
rates of i m pair me nt a n d r ec o ver y of Q O L 1-year after b ot h H C T m o dalities. Ot her s mall st u dies assesse d t he 
traject ories of Q O L i m pair me nts after m yel o a blati ve H C T a n d c o n v e nti o nal c he m ot hera p y a m o n g relati vel y 
y o u n g patie nts wit h c o ntr a dicti n g r es ults o n w hic h a p pr oac h res ulte d i n l o w er Q O L [ 5 0, 5 1]. T o date, n o st u dies 
ha ve bee n carrie d o ut t o ass ess w het her re d u ce d -i nte nsit y all o ge nei c H C T is ass ociate d wit h acce pt a ble Q O L 
a m o n g ol der patie nts wit h c o m or bi dities c o m pare d t o t hera p y. T his i nf or m ati o n is of great i m p orta n ce f or 
decisi o n - ma ki n g a n d will be a d dress e d u n der S pecific Ai m # 3 . 
 
3. 5 R ole of p atie nt prefere nces, p h ysici a n perce pti o n, a n d s oci oec o n o mic f act o rs i n decisi o n -m a ki n g a n d 
o utc o mes :  
 
D ata ar e li mite d o n patie nt treat me nt c h oices i n t h e setti n g of A M L  [ 5 2]. We will use a well -acce pte d 
si n gle ite m meas ur e of p atie nts’ desire d i n v ol ve m e nt i n me dical decisi o n ma ki n g [ 5 3]. T his meas ure was 
pre vi o usl y us e d t o s ur ve y 4 3 6 ne wl y di a g n ose d ca ncer p atie nts a n d 4 8 2 m e m bers of t he ge neral p u blic. 
Prefere nces wer e elicite d usi n g t w o car d s ort pr o ce d ures, eac h of w hic h descri be d fi ve p ote ntial r oles i n 
decisi o n ma ki n g. Fi n di n gs s u g geste d t h at t he i m pact of bei n g dia g n ose d wit h a life- t hreate ni n g ill ness ma y 
i nfl ue nce pr efere n ces t o partici pate. T he m aj orit y ( 5 9 %) of p atie nts wa nte d p h ysicia ns t o ma k e treat me nt 
decisi o ns o n t heir be half, b ut 6 4 % of t he p u blic t h o u g ht t he y w o ul d w a nt t o select t heir o w n treat me nt if t he y 
de vel o pe d ca ncer. S oci o- de m o gr a p hic varia bles acc o u nte d f or o nl y 1 5 % of varia nce i n prefere nces, s u g gesti n g 
t hat t hese varia bles h a ve li mite d r ole i n ma ki n g pre dicti o ns a b o ut patie nts’ decisi o n-ma ki n g st yle. T he meas ure 
ha d a gra d e 6 r ea di n g le v el, g o o d f ace, a n d c o nt e nt vali dit y, a n d g o o d reli a bilit y wit h a Cr o n b ac h’s α = 0. 9 5 
[ 5 4, 5 5].  
 
 
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B ot h patie nt a n d p h ysicia n meas ures w ere rece ntl y vali date d a m o n g 4 3 ol der patie nts wit h a d va nce d 
A M L c h o osi n g b et wee n i n d ucti o n c he m ot hera p y a n d n o n- i nte nsi ve c he m ot hera py/ best s u p p orti ve care [ 5 2] . I n 
t otal, 6 3 % of all patie nts re p orte d n ot bei n g offere d ot her treat me nt o pti o ns des pite p h ysici a n d oc u m e ntati o n of 
alter nati ves. T he s a me st u d y de v el o pe d a m eas ure assessi n g esti mates  of c ure a n d s ur vi val. T h e st u d y s h o w e d 
t hat patie nt a n d p h ysi cia n esti mates of c ur e differe d si g nifica ntl y a n d t hat re gar dless of treat me nt c h oice, 
patie nts re p orte d n ot bei n g offer e d treat me nt o pti o ns a n d o veresti mate d t heir c ha nces of c ure.  
 
S oci oec o n o mic stat us c o ul d i m pact c h oice of treat me nt, access t o s pecialize d care, a n d/ or s ur vi val of 
ca ncer patie nts. Zi p c o d e of patie nt’s pri mar y resi de nc y has bee n use d t o esti mate pr o xi mit y t o treat me nt 
ce nters. I n ge neral me dical practice, pr o xi mit y t o s pecialize d cli nical facilities has bee n s h o w n t o i nfl ue nce 
access t o healt hcare a n d o utc o mes [ 5 6]. T hese fi n di n gs were als o c o nfir me d i n t he setti n gs of ca ncer [ 5 7, 5 8]. 
Li ke wis e, dista nce fr o m ce nters s pecialize d i n H C T see me d t o affect s ur vi val. Patie nts fr o m r ural areas treate d 
wit h a ut ol o g o us H C T were f o u n d t o ha v e a n 1 8 % i ncreas e d relati ve m ort alit y rat e c o m pare d t o t h ose fr o m 
ur ba n ar eas [ 5 9]. I n all o ge neic H C T, dri vi n g ti me t o tra ns pla nt ce nters was f o u n d t o i n de pe n de ntl y i m pact 
s ur vi val. T his effect was i n versel y relat e d t o t he fre q ue nc y of cli nic visits t o t he tra ns pla ntati o n ce nt er [ 6 0]. T his 
is n ot s ur prisi n g si nce all o ge n eic H C T is us uall y ass ociate d wit h seri o us c o m plicati o ns s uc h as graft- vers us- h ost 
disease ( G V H D) a n d i nfecti o n p artic ularl y a m o n g ol der a n d me dicall y i nfir m patie nts. Detecti o n a n d 
ma na ge me nt of t hes e c o m plicati o ns w o ul d re q uire hi g h le v el of pr o m pt ness, a l o w t hres h ol d t o i nter ve ne, a n d 
hi g hl y s pecialize d e x peri e nce [ 6 1].  
 
Resi de ntial zi p c o des of patie nts ha ve als o bee n use d t o esti mate i nc o me, w here l o w er i nc o me was 
f o u n d t o carr y p o or pr o g n ostic ris k [ 6 2]. H o we ver, usi n g zi p c o de t o esti mate b ot h dista nce t o treat m e nt ce nters 
a n d i nc o me w o ul d pre v e nt e x pl ori n g i nteracti o n b et wee n t hes e t w o fact ors. I n t he c urre nt pr ot oc ol , we will use 
patie nts’ zi p c o des t o cal c ulate dri vi n g ti me bet wee n t heir pri mar y resi de nce a n d treat me nt ce nters,  a n d t he n use 
t his i nf or mati o n t o a dj ust f or t he c o m paris o ns bet wee n patie nts w h o were offere d vers us n ot offere d all o ge n eic 
H C T a n d i n t he c o m paris o n of o utc o mes bet wee n t he t w o treat me nt gr o u ps. Patie nt -re p orte d i nc o m e will be 
c ollecte d i n de pe n de ntl y usi n g t he st u d y q uesti o n n aires. 
 
T he healt h care of a n ol d er patie nt wit h ca n cer s h o ul d i ncl u de d o mai ns be y o n d t he tra diti o nal 
ma na ge me nt of ca ncer. Alt h o u g h e v al uati o n of c o m or bi dities a n d perf or m a nce stat us are critical c o m p o ne nts, 
t he y ca n be c o m ple me nte d b y ot her d o mai ns of geriatric assess me nt ( G A ) e val uati n g p h ysical, c o g niti ve, 
affecti ve, s ocial, fi na n cial, a n d ot her fact ors t hat c o ul d affect t he healt h of a n ol der a d ult. T he Nati o nal 
C o m pre he nsi ve Ca ncer Net w or k t o get her wit h t he I nter n ati o nal S ociet y f or Geriatri c O nc ol o g y ha v e 
rec o m me n de d t h e r o uti ne use of a G A f or patie nts of ≥ 6 5 years w h o are dia g n ose d wit h ca ncer [ 6 3]. Be nefits 
ra n gi n g fr o m pr e dicti o n of t o xicit y a n d s ur vi v al t o assista nce i n treat me nt decisi o ns a n d i m pr o vi n g o verall well-
bei n g of ol der ca ncer pati e nts ha ve bee n pr o ve n i n n o n- tra ns pla nt setti n gs [ 6 4- 6 6]. W hile c o m or bi dities pr o vi de 
data o n or ga n- s pecifi c p h ysi ol o gic c ha n ges, frailt y i n dices assess t he ofte n decli ni n g p h ysi ol o gic reser ve of 
m ulti ple s yste ms t hat is as a feat ur e of a gi n g. Frailt y ca n be ma nifeste d b y wei g ht l oss, wea k ness, relati ve 
i m m o bilit y, e x ha usti o n, a n d decrease i n p h ysical acti vit y. It ca n b e ca pt ure d b y differe nt t o ols; o ne of t he m ost 
c o m m o nl y use d a n d pr o v e n se nsiti ve f or pr e dicti o n of s ur vi val of ca ncer patie nts is t he Frailt y I n de x [ 6 7].  
  
 
 
F u ncti o nal stat us is a c o m p o ne nt of G A. It is tra diti o nall y assesse d b y p erf or ma nce stat us ( P S ) scales i n 
tra ns pla nt setti n gs. H o w e ver, res ults i n geriatric o nc ol o g y h a ve s h o w n P S scales t o u n deresti mate t he ma g nit u de 
of f u ncti o nal i m pair me nt i n ol der patie nts w he n c o m pare d t o t he m ore c o m pre he nsi ve ass ess me nts pr o vi de d b y 
use of basic ( B A D L) a n d i nstr u me ntal (I A D L) acti vities of dail y li vi n g  [ 6 8, 6 9]. I A D L, i n partic ular, was s h o w n 
t o pre dict O S of ol der patie nts wit h ne wl y dia g n os e d A M L i n de pe n d e nt fr o m a ge, P S, or c yt o ge netics [ 6 8, 6 9]. 
Meas ure me nt of gait s pee d is a si m ple a n d o bjecti ve t o ol t hat pr o ves t o be ver y usef ul f or pre di cti n g f u ncti o nal 
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decli ne, life -e x pecta nc y, a n d m ortalit y after t hera p y [ 7 0]. It was als o s h o w n t o be as i nf or mati ve as a p h ysical 
perf or ma n ce b atter y  [ 7 1]. Li ke wis e, assess me nts of c o g niti o n, n utriti o n, ps yc h os o cial stat us, a n d s o cial s u p p ort 
ha ve all bee n s h o w n t o pre dict treat me nt t olera nce, s ur vi val , a n d a bilit y t o c o m pl y wit h treat me nt i nstr ucti o ns.  
  
 
T he pr o g n ostic si g nifi ca n ce of G A has n ot bee n a d e q u atel y teste d i n t he tra ns pla nt setti n g. O ne 
preli mi nar y s mall st u d y of 1 6 6 patie nts has s h o w n t hat G A c o ul d u nc o ver a d diti o nal i m pair me nts i n healt h 
be y o n d t h os e ca pt ur e d b y P S [ 7 2]. H o we ver, t he st u d y c ollect e d data o n p atie nts a ge d fr o m 5 0 years, a n d o nl y 4 
of t hese were a ge d ≥7 0 years. I d e ntif yi n g t h ose c o m p o ne nts of G A t hat mi g ht a d d pr o g n ostic i nf or m ati o n t o 
c urre nt pr e-tr a ns pla nt ass ess me nt t o ols w hile n ot a d di n g a s u bsta ntial b ur d e n o n patie nts or tra ns pla nt tea ms 
re q uires a n a de q u atel y-si ze d nati o nal st u d y. We will use here t he Frie d Frailt y i n de x t o ca pt ure frailt y a m o n g all 
patie nts a n d d o mai ns t o c o ver p h ysical, c o g niti ve, ps yc h os o cial, a n d ot her geriatric pr o bl e ms a m o n g patie nts 
w h o are 6 0 years or ol der.  
 
3. 6 I ntr o d uci n g t he use of C o m or bi dit y I n dices i n C o m p ar ati ve Effecti ve ness Rese a rc h of all o ge neic 
H C T:    
U ntil 2 0 0 4, t here has bee n al m ost n o eff ort t o e val uate t he distri b uti o n of c o m or bi dities a m o n g H C T 
reci pie nts, t o i n vesti gate t heir i m pacts o n H C T o utc o mes, or t o i ncl u de t he m i n desi g ni n g cli nical trials. We 
be ga n s yste matic a n al ys es of t he r oles of c o m or bi dities o n H C T o utc o mes usi n g a n o n- tra ns pla ntati o n s pecific 
c o m or bi dit y i n de x, na mel y t he C CI. T he st u d y ass esse d t he cli nical pretra ns pla nt differe n ces bet w ee n 
n o n m yel oa bl ati ve a n d m yel o a blati ve reci pie nts of u nrelate d H C T t o deter mi ne if t he n o n m yel o a blati ve re gi m e n 
tr ul y e x pa n de d t he H C T o pti o ns t o a ne w gr o u p of patie nts. T o t hat e n d, ass ociati o ns bet wee n t he C CI, as a 
meas ure of c o m or bi dities, a n d ot her k n o w n ris k fact ors wit h p ost- H C T N R M a n d s ur vi val were e v al uate d.  
Ga u gi n g b y t h e C o m m o n T o xicit y Criteria ( C T C ) of t he Nati o nal Ca ncer I nstit ute ( N CI), n o n m yel o a blati ve 
patie nts ha d less ( 3 2 % vers us 6 9 %, P < 0. 0 0 0 1) o v erall gra de I V (life- t hreate ni n g) t o xicities t ha n m yel oa blati ve 
patie nts. T he lesse ne d c u m ulati ve i nci de nces of 1 -year ( 2 0 % vers us 3 2 %, P = 1. 4) N R M a m o n g 
n o n m yel oa bl ati ve patie nts di d n ot reac h statistical si g nifica n ce. After a dj ust me nt f or pretra ns pla nt differe nces, 
i ncl u di n g c o m or bi dit y sc ores, statisticall y si g nifica nt l o wer hazar d rati os ( H R) f or 1-year ( 0. 3, P = 0. 0 4) N R M 
were f o u n d f or n o n m yel o a blati ve patie nts, c o nfir mi n g t he i m p orta nce of a si n gle sc ori n g s yst e m f or 
c o m or bi dities. I n m ulti variate a nal ys es of ris k fact ors f or o utc o mes, c o m or bi dities as sc ore d b y t he C CI, pr o ve d 
t o be t he o nl y i n de p e n de nt fact or f or pre dicti n g o verall gra d e I V t o xicit y a n d N R M.  
 
3. 7 De vel o p me nt of t he H C T -CI:  
 
T he C CI w as f o u n d t o ha ve t w o maj or li mitati o ns a m o n g H C T reci pie nts. First, s o me of t he c o m or bi dities 
descri be d b y C harls o n w ere r arel y e nc o u ntere d d u e eit her t o e xisti n g e x cl usi o n criteria, f or e x a m ple f or he patic 
c o m or bi dities, or lac k of i ncl usi o n of la b orat or y d ata, f or e x a m ple f or p ul m o nar y c o m or bi dities. Sec o n d, t he 
C CI di d n ot ca pt ur e s o me of t he c o m or bi dities t hat were fre q ue ntl y see n a m o n g tra ns pla nt e d patie nts, s uc h as 
i nfecti o ns a n d ps yc hiatri c pr o ble ms. As a r es ult, t he C CI i de ntifie d c o m or bi dities i n o nl y 3 5 % of all patie nts 
a n d 1 2 % of r eci pie nts of m yel oa bl ati ve H C T ( 1 2 %) [ 7 3]. 
I n or der t o a d dress t hes e li mitati o ns, t he C CI was m o difie d i n a wa y t hat better detecte d c o m or bi dities 
a m o n g H C T reci pie nts [ 7 4]. First, t he defi niti o ns of se veral c o m or bi dities w ere m o difie d b y a d di n g pr o gressi ve 
i m pair me nts of diff usi o n ca pacit y of car b o n m o n o xi de ( D L C O) a n d/ or f orce d e x pirat or y v ol u me i n 1-sec o n d 
( F E V 1), left ve ntric ul ar ejecti o n fracti o n ( L V E F) of ≤ 5 0 %, a n d pr o gressi v e ele vati o ns of le v els of bilir u bi n a n d 
he patic tra ns a mi nases t o t he cli nical defi niti o ns of p ul m o nar y, car di ac, a n d he patic c o m or bi dities, res pecti vel y. 
I n a d diti o n, ne w c ut-offs f or ser u m creati ni ne le v els were set t o better defi n e re nal c o m or bi dit y. Sec o n d, all 
c o m or bi dities e nc o u nter e d i n tra ns pla nte d patie nts were i ncl u d e d i n t he ris k assess me nt a nal ysis. 
 
  
 
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Fi g ure 2:  Pre dicti o n of N R M a n d s ur vi val b y H C T-CI sc ores 
a m o n g patie nts of t he vali dati o n set. 
T he st u d y i ncl u d e d 1 0 5 5 patie nts wit h differe nt h e mat ol o gical diseases w h o were gi ve n all o ge neic H C T 
after n o n m yel o a blati ve ( n = 2 4 9) or m yel oa bl ati ve ( n = 7 6 1) c o n diti o ni n g. T w o t hir ds of t he patie nts were 
ra n d o ml y assi g n e d t o a tr ai ni n g set a n d o n e t hir d t o a vali dati o n set. I nte ger wei g hts of c o m or bi dities were 
calc ulate d b ase d o n a dj uste d H Rs fr o m C o x pr o p orti o nal hazar d m o dels of 2- year N R M. T he ne w H C T -CI 
i ncl u de d 1 7 c o m or bi dities ac q uiri n g sc or es fr o m 1 t o 3.  
  
 
I n t he trai ni n g set, H C T-CI sc ores of 0,  1, 2, 3, ≥ 4 pre dicte d 2- year N R M of 9 %, 1 4 %, 2 7 %, 4 1 %, a n d 
4 3 %, res pecti vel y. I n t he vali dati o n set, H C T- CI s c ores s h o w e d hi g h er se ns iti vit y t ha n t he C CI sc ores i n 
ca pt uri n g c o m or bi dities. H C T- CI s c ores of 1 -2 a n d  ≥ 3 were f o u n d i n 3 4 % a n d 2 8 % of patie nts, w hile o nl y 1 0 % 
a n d 3 % of patie nts ha d C CI sc ores of 1 a n d ≥2, res pecti vel y. T he H C T- CI sc ores of 0, 1- 2, a n d ≥3 s h o we d g o o d 
discri mi nati o n of N R M ( 1 4 %, 2 1 %, a n d 
4 1 %) a n d s ur vi val ( 7 1 %, 6 0 %, a n d 3 4 %), 
res pecti vel y (Fi g ure 2 ). T he discri mi nat or y 
ca pacit y of t h e H CI- CI a n d C CI, defi n e d as 
t he a bilit y of t he m o del t o se parat e t h ose 
patie nts w h o s ur vi ve d fr o m t h ose w h o die d, 
were c o m par e d usi n g t he c-statistic or 
c o nc or da n ce i n de x [ 7 5], w hic h was i de ntical 
t o t he area u n d er a recei v er o per ati n g 
c haracteristic c ur ve ( A U C). A c-statistic 
val ue of 1. 0 i n dicate d p erfect pr e dicti ve 
discri mi nati o n a n d a val u e of 0. 5 i n dicate d n o 
a bilit y t o discri mi nate. T he H C T - CI sc or es s h o we d hi g her discri mi nati ve p o wer t ha n t he C CI sc ores b ot h f or 
N R M ( c-statistic of 0. 6 9 2 vers us 0. 5 4 6, P < 0. 0 0 1) a n d s ur vi val ( c-statistic of 0. 6 6 1 vers us 0. 5 6 1, P < 0. 0 0 1). 
T he H C T - CI a n d a s ucci nct c o di n g t o ol f or c o m or bi dities were a d d e d t o o ur  st u d y d oc u m e nts. A n E dit orial 
acc o m pa n yi n g t he p a per e m p hasize d t he i m p orta nc e of t his c o m or bi dit y s c ori n g s yste m, w hic h mi g ht all o w 
refi ne me nts of esti mates of t he o utc o mes of ne wl y re p orte d researc h treat m e nts. [ 7 6] 
 
 
 
 
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4. 0  
P R O P O S A L  
We will i n vesti gate i n a pr os pecti ve , l o n git u di nal, o bser vati o nal, m ulti -i nstit uti o nal st u d y t he fre q u e nc y 
of recei vi n g all o ge neic  H C T a m o n g patie nts wit h A M L or  M D S c o nsi dere d f or i n d ucti o n t hera p y  at m ulti ple  
i nstit uti o ns. O ur  pri mar y  g oal  h ere  is  t o  i n vesti gate  h o w  ofte n  ol der  a n d  me dicall y  i nfir m  A M L  patie nts  are 
referre d  t o  u n der g o  all o ge n eic  H C T.  We  will  c ollect  data  o n  o utc o me-discri mi nati ve  criteria,  s uc h  as  a ge, 
i nte nsit y of i n d u cti o n treat me nt, perf or ma nce stat us, c yt o ge netic ris ks, a n d hi g h w hite bl o o d; i n a d diti o n t o data 
o n  patie nts  a n d  p h ysicia n  attit u des  t o war ds  d ecisi o n -ma ki n g  st yle  a n d  c h oice  of  t h era p y,  s o ci o - de m o gra p hic 
varia bles,  a n d  bas eli ne  Q O L  t o  ass ess  reas o ns  p atie nts  ma y  n ot  be  offere d  all o ge neic  H C T. We will e val uate 
differe n ces  bet w ee n  pati e nts  w h o  recei ve  vers us  t h ose  w h o  d o  n ot  recei ve  all o ge n eic  H C T  b y  c o m pari n g  t he 
pre vi o usl y me nti o ne d c h aract eristics.  
 
We  w o ul d  li ke  als o  t o  u n dersta n d  w h o  be n efits  fr o m  all o ge neic  H C T  a n d  t o  pr o vi de  better  t o ols 
f or 
i de ntif yi n g t hese p atie nts. C o n versel y, it is als o i m p orta nt t o i de ntif y pati e nts f or w h o m all o ge nei c H C T is n ot 
rec o m me n de d  b eca us e  of  relati vel y  hi g h  treat me nt-relate d  m or bi dit y  a n d  m ortalit y.  Ot her  i m p orta nt 
c o nsi derati o ns i n t hese j u d g me nts ar e t he  t o xicit y of treat me nt a n d t he Q O L e x perie n ce d b y s ur vi v ors of eit her 
treat me nt  a p pr oac h.  We  will  o bser ve  t he  t w o  gr o u ps  of  patie nts  w h o  will be  treate d  wit h  all o ge n eic  H C T  or 
c o n ve nti o nal t her a p y o v er 2 4 m o nt hs. O utc o m e c o m paris o ns will be caref ull y a dj us te d f or differe n ces bet w ee n 
patie nts  i n  c o m or bi dities  a n d  o utc o me -discri mi nati ve  criteria,  s oci o -d e m o gra p hi c  fact ors,  decisi o n - ma ki n g 
prefere nces,  a n d  b aseli ne  Q O L  sc ores,  w hic h  w ere  c ollecte d  at  b aseli ne  assess me nt.    T hese  d ata  will  hel p 
i n di vi d ualize f uture treat me nt rec o m me n dati o ns . 
 
 
5. 0  
O B J E C TI V E S  
 
5. 1  
Pri m ar y o bjecti ves 
5. 1. 1  Feasi bilit y of all o ge neic H C T i n ol der a n d me dicall y i nfir m patie nts wit h A M L  
5. 1. 1. 1  Esti mati n g t he pr o ba bilit y of u n der g oi n g all o ge neic H C T a m o n g ol der a n d me dicall y i nfir m 
A M L p atie nts  c o m par e d t o  y o u n ger a n d relati vel y healt hier patie nts . 
5. 1. 1. 2  C o m pari n g t he c har acteristics of patie nts w h o di d vers us di d n ot pr ocee d t o all o ge n eic H C T.  
5. 1. 2  C o m paris o n of o utc o mes a m o n g pr os pecti vel y e nr olle d ol der a n d me dicall y i nfir m A M L p atie nts 
gi ve n all o ge neic H C T v ers us i n d ucti o n t hera p y 
5. 1. 2. 1  N o n -rela ps e m ortalit y ( N R M), o verall ( O S), a n d disease-free s ur vi val ( D F S). 
5. 1. 2. 2  Q O L  
5. 2  
Sec o n d ar y o bjecti ve s 
5. 2. 1  A m o n g  a  s u bset  of  patie nts,  st u d yi n g  t he  i m pacts  of  s o me  p ul m o nar y  f u ncti o n  tests  ( diff usi o n 
ca pacit y  of  car b o n  m o n o xi de,  a n d  f orce d  e x pirat or y  v ol u me  i n  o ne  sec o n d)  a n d plas ma  
bi o mar kers ( C -reacti ve pr otei n, al b u mi n, ferriti n, a n d vita mi n D) o n: 
5. 2. 1. 1  O verall m ortalit y at 8 wee ks after i n d u cti o n t hera p y  
5. 2. 1. 2  Feasi bilit y of all o ge neic H C T  
5. 2. 1. 3  C o m paris o n of o utc o mes bet wee n all o ge neic H C T vers us c o n ve nti o nal t hera p y 
5. 3  
Terti ar y o bjecti ve s 
5. 3. 1  
 
Preli mi nar y  t her a p y  dat a  will  be  use d  t o  de vel o p  sta n dar dize d criteria  f or  t he defi niti o ns  of 
“i nte nsi ve” a n d “less -i nt e nsi ve” treat me nts. P h ysicia ns fr o m ar o u n d t he w orl d will be s ur ve ye d 
a b o ut t heir o pi ni o n of t he i nte nsit y of re gi me ns.   
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5. 3. 2  Pr oject res ults will be disse mi nate d per f u n di n g a ge n c y’ s re q uest usi n g n o vel met h o ds. Met h o ds 
will i ncl u de s ocial me dia, we bsites, vi de os, a n d ne wsletters. Patie nts ma y be as ke d t o a p pear o n 
vi de o. All  met h o ds ha ve t he p ossi bilit y of b ei n g p u blis he d or me nti o ne d i n p u blicati o ns.   
5. 3. 3  A m o n g a s u bset of p atie nts a d mitte d t o t he I C U at a n y ti me p oi nt af ter i n d ucti o n c he m ot hera p y, 
e val uati o n of ris k fact ors ass ociate d wit h 9 0 -da y a n d o verall s ur vi val after I C U a d missi o n.  Rates 
of palliati ve car e r eferrals i n patie nts wit h a n d wit h o ut I C U a d missi o ns will be e x a mi ne d.  
5. 3. 4  C o m paris o n of o utc o mes bet wee n patie nts  wit h sec o n dar y A M L a n d patie nts wit h o ut sec o n dar y 
A M L.  
 
6. 0  
P A TI E N T E LI GI BI LI T Y  
6. 1  
I ncl usi o n Criteri a 
6. 1. 1  Patie nts wit h ne w dia g n oses of n o n -M 3 A M L  (See st u d y d oc u me nt ‘ 2 0 0 8 W H O Classificati o n 
of  A M L’ ) or  hi g h -ris k  M D S,  (See  st u d y  d o c u m e nt  ‘ 2 0 0 8  W H O  Classificati o n a n d  Criteria  f or 
M D S’ ) m yel o pr oliferati ve  ne o plas ms  ( M P N) , or  m yel ofi br osis  ( M F)  ( M D S,  M P N,  or  M F 
s h o wi n g 1 0 % or m ore bl asts i n b o ne marr o w) w h o : 
6. 1. 1. 1  P rese nt f or a n A M L -li ke treat me nt t hat c o ul d pla usi bl y pr o d uce a c o m plete re missi o n ( C R); 
f or e x a m ple i nte nsi ve i n d ucti o n c he m ot hera p y, l o w d ose si n gl e a ge nt c h e m ot hera p y,  h y p o -
met h ylati o n a ge nt, or a si milar t hera p y  
6. 1. 1. 2  P ote ntiall y p ossi ble t o r etrie ve f oll o w - u p rec or ds fr o m t he c olla b orati n g i nstit uti o n or treati n g 
pri mar y care p h ysicia n . 
6. 1. 2  Patie nts  wit h pri mar y  refra ct or y  or first  rela ps e  prese nti n g  f or  sal va ge  c he m ot hera p y  will  be 
all o we d  
6. 1. 3  Patie nts of > 1 8 years of a ge  a n d are b ei n g treate d b y t he a d ult A M L s er vice . 
6. 1. 4  A ble t o s pea k a n d rea d E n glis h. 
6. 1. 5  Willi n g a n d a ble t o pr o vi de i nf or me d c o ns e nt. 
6. 2  
E xcl usi o n Criteri a  
6. 2. 1  Patie nts of ≤1 7 years of  a ge  or  w h o  are > 1 8  a n d  recei v e  treat me nt  u n der  t he  pe diatri c  A M L 
ser vice. 
6. 2. 2  Patie nts ol der t ha n 8 0 ye ars 
6. 2. 3  Patie nts  wit h  < 6  m o nt hs  pr oject e d  s ur vi val  d ue  t o  acti ve  sec o n d  mali g na nc y  or  ot her  me dical 
pr o ble m. 
 
7. 0  
E N R O L L M E N T  
 
 
T y picall y, A M L -s peci alize d p h ysicia ns at S C C A a n d c olla b orati n g i nstit uti o ns first i nteract wit h t he 
patie nt i n a c o ns ultati o n sessi o n f or a ne wl y di a g n ose d or rela ps e d A M L or A M L -li ke pres e ntati o n. D uri n g t h e 
i nitial c o ns ultati o n sessi o n, p h ysicia ns e x plai n t he dia g n osis of A M L, ris ks a n d be nefits of i n d ucti o n t hera p y 
vers us n o treat me nt. It is c o m m o n t hat a vaila ble cli nical trials f or i n d ucti o n t hera p y are prese nte d t o t he patie nt 
d uri n g t he i nitial c o ns ultati o n. I n s u c h setti n g it will be a p pr o priate f or  p h ysicia ns t o a p pr oac h eli gi ble patie nts 
a b o ut t heir p ote ntial i nter est i n t he o bser vati o nal st u d y. Patie nts c o ul d be a p pr oac he d f or st u d y partici pati o n b y 
healt hcar e pr o vi ders (as part of t he c o ns e nti n g c o nfere n ce) or b y t he pr ot o c ol researc h c o or di nat or. T o facilitate, 
t his disc ussi o n, t he p h ysi cia n ma y use a pre p are d o ne- pa ge d o c u me nt e x plai ni n g t he st u d y or lea ve a pre pare d 
o ne- pa ge l etter wit h t he p atie nt t hat e x plai ns t he st u d y ( See st u d y d o c u me nts ‘ Tal ki n g P oi nts a n d P h ysicia n-
Facilitate d St u d y Letter’ ). E x pla nati o n of t he st u d y c o ul d b e briefe d b y t he p h ysicia ns a n d t he n f urt h er 
e x plai ne d b y t he st u d y c o or di nat or f or p atie nts treate d at t he S C C A a n d b y t he c olla b orat ors’ staff at t he ot her 
sites. A d diti o nall y, t h e st u d y c o or di nat or will be a vaila ble b y p h o ne or e mail t o a ns wer a n y a d diti o n al q uesti o ns 
raise d b y patie nts at a n y of t he c olla b or ati n g sites.  
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T he st u d y pr oce d ures will be o utli ne d a n d patie nts will ha ve a n o p p ort u nit y t o as k q uesti o ns. If 
necessar y, disc ussi o n a b o ut t he st u d y ma y ta ke pl ace b y tel e p h o ne. Si g n e d i nf or me d c o nse nt is re q uire d f or 
e nr oll me nt. If t he patie nt is u na ble t o pr o vi de writte n i nf or me d c o ns e nt pri or t o q uesti o n naire c o m pleti o n 
beca use of l o gistic li mitati o ns, q uest i o n naires c o ul d be c o m plete d o n t he b asis of ver bal c o ns e nt ( See st u d y 
d oc u me nt ‘ St u d y Lett ers a n d  P h o ne Scri pt f or C o nse nti n g). H o we ver, n o researc h d ata will be e nt ere d i nt o t he 
data base u ntil writte n c o nse nt is d oc u me nte d. We e x pect t he nee d f or ver b al c o nse nt pri or t o writte n c o nse nt t o 
be rare; pri orit y will be t o c o nse nt ri g ht f oll o wi n g a cli nic visit. If recr uit me nt ca n n ot be c o m plete d i n pers o n, 
pri orit y will g o t o c o ntacti n g t he patie nt o v er t he p h o ne, usi n g t he p h o n e scri pt.  D uri n g t he c o ns e nti n g pr o cess, 
if t he patie nt i n dicates t h e y d o n ot w a nt t o partici pate i n all as pects of t h e st u d y, t he y ca n mar k  t his o n t he 
c o nse nt f or m. Patie nts t hat fail t o c o nse nt t o t he st u d y will be as k e d t o fill o ut a c o nse nt fail ure f or m t o 
u n dersta n d t he r eas o ns b e hi n d decli ni n g t h e st u d y. T his f or m will n ot c ollect a n y i de ntif yi n g i nf or m ati o n a n d 
will o nl y rec or d a ge, ge n der, race a n d et h nicit y, a n d mai n reas o n f or n ot w a nti n g t o c o nse nt t o t he st u d y. We 
will kee p t hese files i n a sec ure d ata bas e i n defi nit el y.   
 
E ac h patie nt’s o n c ol o gist will als o partici pate i n t he st u d y t o pr o vi de t h eir assess me nt of t he patie nt’s 
prefere nces f or i n v ol ve m e nt i n treat me nt decisi o n ma ki n g, a n d t h eir esti mates of t he patie nt’s c ha nces of c ure 
a n d s ur vi val. T he o nc o l o gists are li kel y t o pr o vi d e esti mates f or se veral of t he researc h p artici pa nts. F or t heir 
first assess me nt, t he y will be pr o vi de d wit h a writt e n  e x pla nati o n of t he st u d y. T his will be c o nsi dere d t heir 
c o nse nt d oc u me nt, a n d b y pr o vi di n g i nf or mati o n o n t he assess me nt, t he y are c o nse nti n g t o partici p ate i n t he 
st u d y. We will n ot re q uir e t he p h ysicia n t o pr o vi d e writte n c o nse nt.  
 
T o de vel o p sta n dar dize d criteria f or t he defi niti o ns of “i nte nsi ve” a n d “less- i nte nsi ve” treat me nt, we will 
c o n d uct a s ur v e y of r e n o w ne d e x perts s pe cializi n g i n t he treat me nt of ac ute m yel oi d le u k e mia ( A M L). E x perts 
will be a p pr oac h e d b y e mail wit h a li n k t o a brief s ur ve y usi n g t h e Researc h Electr o nic D ata Ca pt ure ( R E D Ca p) 
we bsite (see E x pert S ur ve y ). T he s ur v e y will i ncl u de vari o us treat me nt re gi me ns a n d t he p artici pa nt is as ke d t o 
select eit her “less-i nte nsi ve”, “i nte nsi ve”, or “ u ns ure” f or eac h re gi me n. A m o n g t h ose re gi me ns c h ose n as 
“i nte nsi ve”, t he e x perts will be as ke d t o deter mi n e w het her re gi me ns are of “ hi g h ” or “i nter me diate” i nte nsit y. 
T he s ur ve y will be d o ne i n t w o (testi n g a n d v ali dati o n) sa m ples of 4 0-5 0 e x perts. We see k 8 0 % a gree me nt rate 
o n eac h r e gi me n .. 
 
 
8. 0  
E V A L U A TI O N A N D E N D P OI N T S  
 
T he a p pr o xi mate ti mi n g f or a d mi nistrati o n of t he assess me nts f or t his st u d y is detaile d i n T a ble  1  a n d 
Fi g ure 3 . A d mi nistrati o n of all assess me nts will be e ve nt-dri ve n b ut will a p pr o xi matel y c orres p o n d t o t he ti me 
p oi nts ill ustrate d i n T a ble 1 a n d Fi g ure  3 . T h ese ti me p oi nts are rec o m m e n de d d ates t hat c o ul d b e c o m plete d  
wit hi n a li mit of 3 0 da ys fr o m t he pr o p os e d ti me p oi nts t o ta ke i nt o acc o u nt s uita bilit y of patie nts’ cli nical stat us 
a n d reas o n a ble r ec o ver y of peri p her al bl o o d c o u nts.  
 
P atie nts w h o are offer e d a n d t he n treat e d wit h H C T  will  ha ve assess me nts  d o ne at a p pr o xi matel y 3, 6, 
1 2, a n d 1 8  m o nt hs aft er da y 0 of H C T. F or p atie nts treate d wit h n o n -H C T treat me nts (a d diti o nal c o n ve nti o nal 
t hera p y or f oll o w u p/s u p p orti ve care), assess me nts will be d o ne at ti me p oi nts t hat are r o u g hl y c orres p o n di n g t o 
t h ose w h o recei ve d tr a ns pla nts, w hic h will be at a p pr o xi matel y 9, 1 2, 1 8, a n d 2 4 m o nt hs fr o m st u d y e nr oll me nt. 
Patie nts w h o ha ve n’t recei ve d f urt h er tr eat me nt after 6 m o nt hs fr o m date of st u d y e nr oll me nt s h o ul d f oll o w t he 
ti me p oi nts f or assess me nts f or n o n-H C T treat me nts. S h o ul d t hese patie nts later b e treate d  wit h all o ge n eic H C T, 
t he n dates of assess me nts will be r ea dj uste d t o reflect t h os e desi g ne d f or reci pie nts of H C T ( 3, 6, 1 2, a n d 1 8 
m o nt hs after da y 0 of H C T).  
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8. 1  
 A S S E S S M E N T S  
 
8. 1. 1  P ati e nt -re p orte d s oci o -de m o g r a p hic v ari a bles  
 
8. 1. 1. 1  R ace a n d et h nicit y. 
8. 1. 1. 2  A ge . 
8. 1. 1. 3  Ge n der . 
8. 1. 1. 4  M arital stat us a n d li vi n g sit uati o n . 
8. 1. 1. 5  Reli gi osit y/s pirit ualit y.  
8. 1. 1. 6  W or k stat us. 
8. 1. 1. 7  In c o me . 
8. 1. 1. 8  Ins ura nce stat us . 
8. 1. 1. 9  T o bacc o , alc o h ol, a n d r ece nt f o o d i nta ke hist or y. 
8. 1. 1. 1 0  
Pare nt h o o d. 
8. 1. 1. 1 1  
E d ucati o nal le vel as classifie d i nt o fi ve cate g ories: s o me hi g h sc h o ol or less, hi g h sc h o ol 
gr a d uate, v o cati o nal c oll e ge or s o me c olle ge, c oll e ge de gree, or pr ofessi o nal de gree [ 5 2, 7 7]. 
E d ucati o n is es peciall y i m p orta nt i n o ur st u d y si n ce t he maj orit y of s u bjects are o utsi de t he 
la b or mar ket. 
8. 1. 1. 1 2  
Zi p -c o de of t he pri mar y resi de nce. Eac h zi p -c o de data p oi nt will be ge oc o de d usi n g t he 
Arc GI S  9. 3  Street -Ma p N ort h  A meri ca  P ostal  U. S.  a d dress  l o cater  ( E S RI,  Re dla n ds,  C A). 
T he l ocati o n of t he tr eati n g ce nter will be ge oc o d e d i nt o a se p arate ma p l a yer usi n g t he U. S. 
Streets  a d dress  l ocater.  T he  Arc GI S  Net w or k  A nal yst  e xte nsi o n  ( E S RI)  will  be  use d  t o 
calc ulate  dri vi n g  dista nce  a n d  a vera ge  dri vi n g  ti me  al o n g  t he  street  net w or k  bet wee n  zi p -
c o de of pri mar y resi de n ce t o t he treati n g ce nter f or eac h p atie nt.  
 
T hese vari a bles will be assesse d o nce at:  
1)  St u d y e nr oll me nt . 
 
 
8. 1. 2  A M L  or M D S  di a g n ostic f e at ures  
 
8. 1. 2. 1  I n p eri p her al bl o o d a n d/ or b o ne marr o w, i nf or mati o n o n: 
8. 1. 2. 1. 1  M or p h ol o g ical  dia g n osis  (See  st u d y  d oc u m e nts  ‘ 2 0 0 8  W H O  Classificati o n  of  A M L 
a n d 2 0 0 8 W H O Classificati o n a n d Criteria f or M D S’). 
8. 1. 2. 1. 2  Fl o w c yt o metr y.  
8. 1. 2. 1. 3  C yt o ge netics  a n d m olec ular a b n or malities:  
8. 1. 2. 1. 3. 1  A M L  ris k -classificati o n (See  s t u d y  d oc u me nt  ‘ A M L  Ris k  Stat us  Base d  o n 
C yt o ge netics a n d M olec ular A b n or malities’ ). 
8. 1. 2. 1. 3. 2  M D S feat ures ( See st u d y d oc u me nt ‘I nter nati o nal Pr o g n ostic Sc ori n g S yst e m f or 
M D S’ ). 
8. 1. 2. 1. 4  I nter nati o nal  pr o g n ostic  sc ori n g  s yst e m-Re vise d  (I P S S- R)  f or  patie nts  wit h  M D S 
(See st u d y d o c u me nt ‘I nt er nati o nal Pr o g n ostic Sc ori n g S yste m f or M D S’). 
 
8. 1. 2. 2  I n case of e xtra-me d ullar y diseas e:  
8. 1. 2. 2. 1  Fl o w c yt o metr y of cereb r o-s pi nal fl ui d. 
8. 1. 2. 2. 2  
 
P h ysical e x a mi nati o n assess me nt of a n y s oft tiss ue mass (c hl or o ma).  
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8. 1. 2. 2. 3  I ma gi n g d escri pti o ns of a n y s oft tiss ue mass (c hl or o ma). 
 
T hese vari a bles will be assesse d o nce at:  
1)  St u d y e nr oll me nt.  
 
8. 1. 3  P F T , Bl o o d Tests, a n d Uri ne A n al ysis (f or p atie nts of F H C R C o nl y) 
8. 1. 3. 1  P ul m o nar y  f u n cti o n  tests:  partic ularl y,  diff usi o n  ca pacit y  of  car b o n  m o n o xi de  ( D Lc o)  after 
c orrecti o n f or he m o gl o bi n a n d f orce d e x pirat or y v ol u me i n o ne sec o n d ( F E V 1).  
8. 1. 3. 2  Ser u m  ferriti n, al b u mi n, C-reacti ve pr otei n ( C R P), a n d vita mi n D . 
8. 1. 3. 3  Uri ne test: Al b u mi n -creati ni ne rati o, as well as uri ne a nal ysis.  
 
T hese vari a bles will be assesse d o nce at:  
1)  S t u d y e nr oll me nt.  
 
8. 1. 4  H C T -CI, c o m or bi dities, a n d l a b or at or y tests: 
 
8. 1. 4. 1  Left  ve ntric ul ar  ej ecti o n  fracti o n,  if  a vaila ble  or  cli nicall y  i n dicate d.  T he  cl osest  val ue 
(i ncl u de t he d ate) t o t he st u d y ass ess me nt p oi nt. Li ver f u n cti o n tests: partic ularl y, t otal a n d 
direct  bilir u bi n,  as partat e  a m i n otra nsferase,  ala ni ne  a mi n otra nsferase,  a n d  al b u mi n. T he 
cl osest val ues (i ncl u de t h e dates) t o t he st u d y assess me nt p oi nt.  
8. 1. 4. 2  Wei g ht a n d hei g ht a n d  calc ulati o n of b o d y mass  i n de x. T he cl osest meas ure me nts (i ncl u de 
t he dates) t o t he st u d y assess me nt p oi nt  
8. 1. 4. 3  L a b orat or y t ests, if a vail a ble or cli nicall y i n dicat e d: T he cl osest val u es (i ncl u de t he dates) t o 
t he st u d y ass ess me nt p oi nt: 
8. 1. 4. 3. 1  A bs ol ute ne utr o p hil c o u nt. 
8. 1. 4. 3. 2  He mat ocrit perce nta ge.  
8. 1. 4. 3. 3  Platelet c o u nt.  
8. 1. 4. 3. 4  Ser u m creati ni ne.  
8. 1. 4. 3. 5  Lactate d e h y dr o ge n ase.  
8. 1. 4. 3. 6  Ser u m ferriti n.  
8. 1. 4. 3. 7  Beta - 2 micr o gl o b uli n.  
8. 1. 4. 4  H C T -CI t otal sc or e a n d p ositi ve c o m or bi dit y fi n di n gs ( Please see st u d y d o c u me nts f or H C T-
CI  a n d  t he  c o m or bi dit y  c o di n g  t o ol).  If  s o me  of  t he  c o m or bi dities  i ncl u de d  i n  t he  H C T -CI 
were n ot ass esse d f or a p atie nt, t he n i n dicate n ot a vaila ble or  “ N A”.  
8. 1. 4. 5  Ot her p ositi ve c o m or bi dities, w hic h are n ot i ncl u d e d i n t he H C T-CI.  
 
T hese vari a bles will be assesse d at:  
1)  S t u d y e nr oll me nt.  
2)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle. 
3)  After  a p pr o xi matel y  6 m o nt hs  fr o m  st u d y  e nr oll me nt  a n d,  if  necessar y,  a dj uste d  wit hi n  a 
li mit of 30 da ys t o ha v e t his assess me nt d o ne p ri or t o treat me nt wit h eit her all o ge nei c H C T 
or a d diti o nal n o n-tra ns pl a nt t hera pies.  
 
8. 1. 5  K ar n ofs k y perf or m a nce st at us ( K P S) perce nt a ge : 
 
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Please see st u d y d oc u me nt ‘ T he Kar n ofs k y Perf or ma nce Stat us Scale’  f or K P S assess me nt. 
 
8. 1. 5. 1  As pr os pecti vel y ass esse d  a n d d oc u me nte d b y cli nicia ns.  
8. 1. 5. 2  If n ot assesse d b y cli nicia ns at t he re q uire d st u d y ti me p oi nts: t here t w o o pti o ns. 
8. 1. 5. 3  Re q uest K P S assess me nt fr o m treati n g  p h ysicia n.  
8. 1. 5. 4  Assi g n me nt  of  K P S  b y  st u d y  c o or di nat ors  at  t h eir  res p ecti ve  sites  after  re vie w  of  me dical 
rec or ds. 
8. 1. 5. 5  S o urce of K P S assess me nt s h o ul d be n ote d (cli nicia n vers us st u d y c o or di nat or) 
 
K P S will be assesse d at:  
1)  St u d y e nr oll me nt.  
2)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
3)  After  a p pr o xi matel y  6  m o nt hs  fr o m  st u d y  e nr oll me nt  a n d,  if  necessar y,  a dj uste d  wit hi n  a 
li mit of 30 da ys t o ha v e t his assess me nt d o ne pri or t o treat me nt wit h e it her all o ge nei c H C T 
or a d diti o nal n o n-tra ns pl a nt t hera pies.  
4)  At 9, 1 2, 1 8, a n d 2 4 m o nt hs fr o m st u d y e nr ol lm e nt f or p atie nt n ot treate d wit h H C T  or at 3, 
6, 1 2, a n d 1 8 m o nt hs after da y 0 of all o ge n eic H C T f or reci pie nts of H T C.  
 
8. 1. 6  P ati e nt pref ere nce s ur v e ys : 
 
8. 1. 6. 1  Patie nt -re p orte d  s ur ve y (See  st u d y  d o c u me nt  ‘ Patie nt  Prefere nce  s ur ve y ) will  c ollect 
i nf or mati o n o n: 
8. 1. 6. 1. 1  Patie nts’ p referre d l e vel of i n v ol ve me nt i n treat me nt decisi o n-ma ki n g [ 5 3]. 
8. 1. 6. 1. 2  Patie nts’ val ues re gar di n g le n gt h of life vs. Q O L. 
8. 1. 6. 1. 3  Patie nts’  perce pti o ns  of  t he  ris ks  a n d  b e nefits  of  all o ge nei c  H C T  vers us  ot her 
t hera pies. 
8. 1. 6. 1. 4  Patie nts’ c o nfi de nce i n t heir k n o wle d ge a b o ut all o ge n eic H C T vers us o t her t hera pies. 
8. 1. 6. 1. 5  Patie nts’ esti mates of t heir c ha nces of c ure a n d s ur vi val at 1 -year.  
 
T hese vari a bles will be assesse d at:  
1)  St u d y e nr oll me nt.  
2)  After  a p pr o xi matel y 1 m o nt h fr o m st u d y e nr oll me nt a n d  at least 2 8 da ys  fr o m last t hera p y 
c ycle.  
3)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
4)  After a p pr o xi matel y 6 m o nt hs fr o m st u d y e nr oll me nt if t he patie nt has n ot u n der g o ne H C T.  
 
 
8. 1. 7  P h ysici a n- re p orte d s ur ve ys:   
8. 1. 7. 1  8. 1. 7. 1 P h ysicia n -re p orte d s ur ve y (See st u d y d oc u me nts ‘ M D De m o gra p hi cs s ur ve y a n d M D 
S ur ve y’ ) will c ollect i nf or mati o n o n:  
8. 1. 7. 1. 1  
 
P h ysicia ns’ c har acteristics .  
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8. 1. 7. 1. 2  P h ysicia ns’ assess me nt  of  t heir  res p ecti ve  p atie nts’  prefere nces  f or i n v ol ve me nt  i n 
treat me nt decisi o n ma ki n g usi n g De g n er’s v ali date d t o ol [ 5 3]. 
8. 1. 7. 1. 3  P h ysicia ns’ esti mates of  t heir res pecti ve patie nts’ c ha nces of c ure a n d s ur vi val at 1 -
year.  
 
T hese vari a bles will be assesse d at:  
1)  St u d y e nr oll me nt.  
2)  After  a p pr o xi matel y 1 m o nt h fr o m st u d y e nr oll me nt a n d  at least 2 8 da ys  fr o m last t hera p y 
c ycle. 
3)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle. 
4)  After a p pr o xi matel y 6 m o nt hs fr o m st u d y e nr ol l me nt if t he patie nt has n ot u n der g o ne H C T.  
 
 
8. 1. 8  A v ail a bilit y  of d o n or: 
 
We will c ollect i nf or mati o n o n:  
8. 1. 8. 1  W het her t he patie nt has a p ote ntiall y a v aila ble d o n or. 
8. 1. 8. 2  W het her t he patie nt has a defi nitel y a vaila ble d o n or. 
8. 1. 8. 3  T y pe of d o n or: r elate d, u nrelate d, or c or d bl o o d. 
8. 1. 8. 4  De gree  of  H L A -matc hi n g:  matc he d,  si n gle  allele  mis matc h,  o ne  a nti ge n  mis matc h,  H L A -
ha pl oi de ntical, or ot hers. 
 
T hese vari a bles will be assesse d at:  
1)  St u d y e nr oll me nt.  
2)  After  a p pr o xi matel y 1 m o nt h fr o m st u d y e nr oll me nt a n d  at least 2 8 da ys  fr o m last t hera p y 
c ycle. 
3)  After  a p pr o xi matel y  6  m o nt hs  fr o m  st u d y  e nr oll me nt  a n d,  if  necessar y,  a dj uste d  wit hi n  a 
li mit of 3 0 da ys t o ha v e t his assess me nt d o ne pri or t o treat me nt wit h eit her all o ge nei c H C T 
or a d diti o nal n o n- tra ns pl a nt t hera pies.  
 
8. 1. 9  Tre at me nt det ails : 
 
8. 1. 9. 1  T hera p y  d etails : 
8. 1. 9. 1. 1  Cli nical trial or n ot.  
8. 1. 9. 1. 2  Na me of c o m bi nati o n t hera p y. 
8. 1. 9. 1. 3  Na mes of eac h tr eat me nt a ge nt .  
8. 1. 9. 1. 4  Details o n d oses a n d d urati o n of eac h t h era p y a ge nt. 
 
T hese vari a bles will be assesse d at:  
1)  All ti me - p oi nts after  e nr oll me nt. 
 
8. 1. 9. 2  All o ge n eic H C T :  
8. 1. 9. 2. 1  Cli nical trial or n ot. 
8. 1. 9. 2. 2  T y pe of d o n or gr aft recei ve d: relate d, u nrelate d, or c or d bl o o d. 
8. 1. 9. 2. 3  
 
De gree  of  H L A -matc hi n g  of  graft  recei ve d:  mat c he d,  si n gle  allele  mis matc h,  o ne 
a nti ge n mis matc h, H L A - ha pl oi de ntical, or ot hers. 
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8. 1. 9. 2. 4  T y pe of ste m cell s o urce: marr o w, peri p heral bl o o d, or c or d bl o o d. 
8. 1. 9. 2. 5  T y pe of c o n diti o ni n g re gi me n: na me of a ge nts, d oses, a n d d urati o ns. 
8. 1. 9. 2. 6  C M V ser ol o g y stat us of patie nt a n d d o n or. 
8. 1. 9. 2. 7  Di d ac ute G V H D de v el o p: date, gra de, treat me nts gi ve n f or ac ute G V H D ? 
8. 1. 9. 2. 8  Di d c hr o nic G V H D de v el o p: date, gra de, treat me nts gi ve f or c hr o nic G V H D?  
8. 1. 9. 2. 9  Di d t he patie nt r ela pse after tra ns pla nt: if yes, d ate a n d det ails o n a n y treat me nt gi ve n 
f or rela ps e? 
8. 1. 9. 2. 1 0  If t he patie nt r ecei v e d sec o n d tra ns pla nt: sa me q u esti o ns a b o ut ti me of tra ns pla nt. 
 
T hese vari a bles will be assesse d at:  
1)  After a p pr o xi matel y 9, 1 2, 1 8, a n d 2 4 m o nt hs aft er st u d y e nr oll me nt or c orres p o n di n g dates 
of 3,  6, 1 2, 1 8 m o nt hs after H C T. T hes e dates ca n be a dj uste d wit hi n a li mit of 3 0 da ys t o 
ha ve t his assess me nt d o ne pri or t o treat me nt wit h eit her all o ge neic H C T or a d diti o nal n o n -
tra ns pla nt t hera pies.  
 
 
8. 1. 1 0  A M L or M D S res p o nse e v al u ati o ns : 
 
8. 1. 1 0. 1  
A M L or M Ds disease stat us i n peri p heral bl o o d a n d/ or b o ne marr o w as f oll o ws:  
8. 1. 1 0. 1. 1  M or p h ol o g y. 
8. 1. 1 0. 1. 2  Fl o w c yt o metr y.  
8. 1. 1 0. 1. 3  C yt o ge netics.  
8. 1. 1 0. 1. 4  Fl u oresce nce i n sit u h y bri dizati o n ( FI S H). 
8. 1. 1 0. 1. 5  M olec ular mar k er a b n or mal ities. 
 
8. 1. 1 0. 2  
I n case of e xtra-me d ullar y diseas e:  
8. 1. 1 0. 2. 1  Fl o w c yt o metr y of cereb r o-s pi nal fl ui d. 
8. 1. 1 0. 2. 2  P h ysical e x a mi nati o n assess me nt of a n y s oft tiss ue mass (c hl or o ma).  
8. 1. 1 0. 2. 3  I ma gi n g d escri pti o ns of a n y s oft tiss ue mass (c hl or o ma). 
 
8. 1. 1 0. 3  
Disease r es p o nses:  
8. 1. 1 0. 3. 1  A M L acc or di n g t o t he re vise d rec o m me n d ati o ns of t he I nter n ati o nal W or ki n g Gr o u p 
(I W G) f or r es p o nse criteria a n d treat me nt o utc o m es ( please, see st u d y d oc u me nt 
‘ A M L Res p o nse Criteria’).[ 7 8] 
8. 1. 1 0. 3. 2  M D S  acc or di n g  t o  t h e  m o difie d  I W G  res p o nse  criteria  ( pleas e,  see  st u d y  d o c u me nt 
‘ M D S Res p o nse Criteria’).[ 7 9] 
 
T hese e v al uati o ns will be assesse d at:  
1)  After  a p pr o xi matel y 1 m o nt h fr o m st u d y e nr oll me nt a n d  at least 2 8 da ys  fr o m last t hera p y 
c ycle.  
2)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
3)  After a p pr o xi matel y 6 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
4)  A t 3, 6, 1 2, a n d 1 8 m o nt hs after da y 0 of all o ge neic H C T f or reci pie nts of H C or at 9, 1 2, 1 8, 
a n d 2 4 m o nt hs fr o m st u d y e nr ol me nt f or patie nt n ot treate d wit h H C T. 
 
 
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8. 1. 1 1  T o xicit y criteri a :  
 
T o xicit y  will  b e  gr a de d  usi n g a n d  a da pte d  versi o n  of  t he  C T C A E  ( N CI  C o m m o n  T er mi n ol o g y 
Criteria f or A d v erse E v e nts) Versi o n 4. 0 ( htt p://cte p.ca n cer. g o v ). A c o p y of t he a da pte d  
C T C A E v 4. 0 is a vaila ble i n st u d y d oc u me nt ‘ A d a pte d C T C’. 
O nl y t o xicities t hat are gr a de d at III or I V will be d oc u me nte d f or t his st u d y. 
 
T hese e v al uati o ns will be assesse d at:  
1)  After  a p pr o xi matel y 1 m o nt h fr o m st u d y e nr oll me nt a n d  at least 2 8 da ys  fr o m last t hera p y 
c ycle.  
2)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
3)  After a p pr o xi matel y 6 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
4)  At  3  a n d  1 8  m o nt hs  after  da y  0  of  all o ge neic  H C T  f or  reci pie nts  of  H T C  or  at  9  a n d  2 4 
m o nt hs fr o m st u d y e nr oll me nt f or patie nt n ot treat e d wit h H C T.  
 
8. 1. 1 2  P h ysic al Perf or m a nce : 
 
T he NI H T o ol b o x 4 -Meter Wal k Gait S pee d Test will be use d t o meas ure l oc o m oti o n. Gait s pee d is 
a n i n dicat or of t he healt h of p h ysi ol o gical s yst e ms. Patie nts will be as ke d t o wal k f o ur met ers at t heir 
us ual pace f or o ne practi ce sessi o n a n d t w o ti me d trials. T his test ta kes t hree mi n utes t o a d mi nister.  
St u d y c o or di nat ors will meet t he patie nts at re g ularl y sc h e d ule d me dical a p p oi nt me nts a n d will as k 
t he m  t o  c o m plete  t his  q uic k  assess me nt. F or  patie nts  wit h  n o  sc he d ul e d  a p p oi nt me nts  wit hi n  t h e 
ra n ge of a d mi nisteri n g t he 4-meter w al k test, st u d y c o or di nat ors will mail a self -a d mi nistere d wal k 
test  s heet  t o  b e  c o m plet e d  b y  t he  patie nt.  Pre vi o us  st u dies  ha ve  s h o w n  t hat  a  s elf -a d mi nistere d, 
a da pte d w al k test (t he H o me -Heart -Wal k) ha d a str o n g i ntra -class c orrelati o n c oefficie nt ( 0. 9 8) wit h 
a sta n dar d wal k test. [ 8 0, 8 1] T he test was well recei ve d b y p artici pa nts w h o ha d a me di a n a ge of 6 4 
(ra n ge: 4 9 – 8 0) years ol d. [ 8 1] T he st u d y c o n cl u de d t hat self -a d mi nistere d wal k test is a relia bl e a n d 
usef ul  met h o d  of  c ollecti n g  p h ysical  acti vit y  dat a  i n  a  me dicall y -c halle n ge d,  ol d er  p o p ulati o n. [ 8 1] 
We will i m ple me nt t he sa me restricti o ns use d i n t hat st u d y b y e x cl u di n g patie nts wit h d oc u me nte d 
heart fail ure, u nsta ble a n gi na pect oris, fe v er, c o m ple x arr h yt h mia, resti n g diast olic blo o d press ure of 
1 0 0 m m H g or m or e or u nsta ble gait  fr o m perf or mi n g t he test o n t heir o w n.[ 8 1]  
 
T his test will be gi ve n at:  
1) St u d y e nr oll me nt. 
2) All ot her  ti me  p oi nts  f or c ollecti o n  of  p atie nt -re p orte d  meas ures;  eit her  perf or me d  b y  st u d y 
staff at a re g ularl y s c he d ule d me dical a p p oi nt me nt at st u d y i nstit uti o n or self -a d mi nistere d b y 
patie nts t hat d o n ot ha ve a c oi nci de ntl y sc he d ul e d me dical a p p oi nt me nt.  
 
8. 1. 1 3  O utc o mes D at a:  
8. 1. 1 3. 1  
Ali v e or decease d . 
8. 1. 1 3. 2  
 
If  deceas e d:  ca us e(s)  of  deat h:  R o ot  ( u n derl yi n g  ca use  of  deat h),  pr o xi mate  (i m me diate 
ca use of d eat h), a n d c o ntri b uti n g ca us es of deat h. 
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1 8 
8. 1. 1 3. 3  
Disease  stat us:  re missi o n,  rela pse,  pr o gressi o n,  persiste nt  disease  s u p p orte d  wit h  b y 
e vi de nce as i n ( A M L r es p o nse e val uati o n). 
8. 1. 1 3. 4  
F or r eci pie nts of all o ge n eic H C T:  
8. 1. 1 3. 4. 1  Di d ac ute G V H D de v el o p or n ot? 
8. 1. 1 3. 4. 1. 1  
If  yes: d at e,  gra d e, or ga ns  i n v ol ve d,  a n d  treat me nts  gi ve n  f or  ac ut e 
G V H D . 
8. 1. 1 3. 4. 2  C urre nt stat us of ac ut e G V H D: acti ve, res ol vi n g, res ol ve d. 
8. 1. 1 3. 4. 3  Di d c hr o nic G V H D de v el o p or n ot? 
8. 1. 1 3. 4. 3. 1  
If  yes:  d ate,  gra de,  or ga ns  i n v ol ve d,  a n d  treat me nts  gi ve n  f or  c hr o ni c 
G V H D . 
8. 1. 1 3. 5  
C urre nt stat us of c hr o nic G V H D: acti ve, res ol vi n g, res ol ve d. 
8. 1. 1 3. 6  
A d missi o n  t o t he ac ute care ser vice wit hi n t he first 6 0 da ys after i n d u cti o n a n d t he first 
6 0 da ys after c o ns oli dati o n. 
8. 1. 1 3. 7  
A d missi o n t o t he I C U at a n y ti me after i n d u cti o n  
8. 1. 1 3. 7. 1. 1  
If  yes: dates of a d missi o n a n d disc har ge fr o m t he I C U a n d h os pital, I C U 
a d missi o n  dia g n osis,  m ost  rece nt  A M L  treat me nt,  a n d  mar kers  of  or ga n  fail ure 
wit hi n  2 4  h o urs  of  I C U  a d missi o n,  i ncl u di n g  bl o o d  c o u nts,  bl o o d  c he mistries, 
vital  si g ns,  a n d  use  of  life  s u p p ort  d e vices  (i n vasi ve  mec h a nical  v e ntilati o n, 
n o ni n vasi ve  p ositi ve  press ure  ve ntilati o n,  vas o press ors,  i n otr o pes,  a n d  di al ysis). 
A d diti o nall y  a n y  p ositi ve  c ult ures  fr o m  1  wee k  pri or  t o  1  w e e k  aft er  I C U 
a d missi o n will be c ollecte d.  
8. 1. 1 3. 8  
Prese nce of palliati ve care referral at a n y ti me p oi nt after referral t o t he S C C A.  
 
8. 1. 1 4  P ati e nt -re p orte d Q O L me as ures  (s ee st u d y d oc u me nt ‘ Patie nt Q uesti o n naire Pac k et ): 
 
Q O L a n d s y m pt o ms will be assesse d l o n git u di nall y usi n g 8 meas ures. All Q O L q uesti o n naires will 
be sc ore d acc or di n g t o t he rec o m me n d ati o ns of t he de vel o pers. We esti mate it will ta ke 1 5 mi n utes 
t o c o m plete t he q uesti o n naires. Please, s ee st u d y d oc u me nt ‘ Patie nt Q uesti o n naire Pac k et’  f or t h e 
meas ures of p atie nt -r e p orte d Q O L.  
 
T he F u ncti o nal Ass ess me nt of Ca ncer T hera p y B o ne Marr o w Tra ns pla nt ( F A C T- B M T, versi o n 4) 
Scale is a 4 9 -ite m patie nt-re p orte d o ut c o me q uesti o n naire t hat meas ures Q O L i n b o n e marr o w 
tra ns pla nt patie nts. T he q uesti o n naire i ncl u des t he sta n dar d f or m of t he F A C T i nstr u me nt, na mel y 
t he F A C T-G a n d a se p ar ate B M T s cale c o nsisti n g of 1 2 ite ms. T he B M T s cale w as e nlar ge d d uri n g 
t he vali dati o n pr oce d ure fr o m 1 2 t o 2 2 ite ms b y Mc Q uell o n et al. [ 8 2] T he F A C T -B M T meas ures 
p h ysical, f u ncti o nal, s oci a l/fa mil y a n d e m oti o nal well- bei n g a n d B M T-s pecific c o ncer ns. All ite ms 
are r ate d o n a fi ve - p oi nt Li kert scale. T h e F A C T i nstr u me nt was rec o m me n de d b y A n dr y k o ws ki f or 
t he i n vesti gati o n of Q O L i n B M T patie nts. [ 8 3] Patie nts will be as ke d t o c o m me nt o n t he state me nts 
wit h re gar d t o t he ti me p eri o d of t he w ee k i m me diatel y prece di n g t h e s pecific st u d y ti me p oi nt.  T o 
lesse n t he b ur de n o n p atie nts, we will o nl y use t h e para meters u n der t h e sta n dar d f or m of F A C T. 
 
 
T he E Q -5 D [ 8 4] will be use d t o ca pt ure p artici pa nt-re p orte d utilities t hat ma y b e use d t o cal c ulate 
q ualit y a dj uste d s ur vi val. T he E Q - 5 D c o ntai ns a fi ve-ite m s ur ve y wit h t hree res p o nse le v els per ite m 
meas uri n g m o bilit y, self - care, us u al acti vities, pai n/ disc o mf ort a n d a n xiet y/ de pressi o n. C o n versi o n 
ta bles all o w sc ori n g fr o m t he 5 ite ms i nt o a s u m mar y utilit y sc ore.  
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T he S ocial Acti vit y L o g ( S A L) was desi g n e d t o ca pt ure t he fre q ue n c y a n d di versit y of s o cial 
acti vities o utsi de of dail y res p o nsi bilities. T he S A L w as a da pt e d b y S yrj ala et al [ 8 5]fr o m o ne of t he 
fe w e xisti n g meas ur es of s ocial acti vit y p artici pati o n, t he Pleasa nt E ve nts Sc he d ule. [ 8 6]T he S A L 
was de vel o pe d t o f oc us o n acti vities of s ur vi v ors wit h pe o ple ot her t ha n t h ose wit h w h o m t he 
s ur vi v ors li ve. T his was d o ne b y re vie wi n g t he ori gi nal c o nte nt of t h e Pleasa nt E ve nts Sc he d ule a n d 
i de ntif yi n g ite ms t hat re prese nte d s oci al acti vities of a d ults. T his c o nte nt w as t he n re vie we d b y a 
f oc us gr o u p of 8 n o n-ca n cer a d ult v ol u nteers w h o c o nsi dere d t heir o w n acti vities of t he pre vi o us 
m o nt h a n d a d de d or r e vise d ite ms. T he res ulti n g ite ms were t h e n c o m plete d b y t w o sets of 
v ol u nteers. I n t hat st u d y, t he S A L p ossess e d g o o d i nter nal c o nsiste nc y ( Cr o n bac h’s α = 0. 8 2). 
I nter nal c o nsiste n c y f or n o n-c o ntact w as α = 0. 8 1, re g ular e ve nts α = 0. 7 5 a n d s pecial e ve nts α = 
0. 6 3. S F- 3 6 s ocial f u n cti o n a n d S A L were m o deratel y c orrelate d (r = . 3 1) as a n e vi de n ce of 
c o n ver ge nt v ali dit y.  
T o f urt her meas ure s o cial s u p p ort, we will use t he E N RI C H D S oci al S u p p ort I nstr u m e nt ( E S SI) 
[ 8 7, 8 8]. T his scale was create d fr o m ite ms fr o m ot her vali date d meas ures of s ocial s u p p ort; t hese 
ite ms were c h os e n f or t h eir d oc u me nte d pre dicti v e vali dit y. U nli ke t he S A L w hic h m eas ure 
o bjecti ve partici pati o n i n s ocial acti vities, t his meas ure ta ps patie nts’ p erce pti o n of s ocial s u p p ort, 
b ot h p h ysical a n d e m oti o nal. T he res p o ns e cat e g ories f or t he se v e n ite ms ra n ge fr o m 1 ( n o n e of t he 
ti me) t o 5 (all of t he ti me). Create d f or use wit h patie nts wit h car diac diseas e, it was f o u n d t o be 
pre dicti ve of d eat h a n d t o ha ve g o o d i nter nal c o nsiste nc y ( Cr o n bac h’s α = 0. 8 6) [ 7 9]. T he s ocial 
s u p p ort meas ure h as als o bee n use d i n t he tra ns pla nt p o p ulati o n b ut res ults are n ot p u blis he d yet 
( S yrjal a K, Pers o nal C o m m u nicati o ns).  
De pressi o n is a c o m m o n ps yc hiatric  c o n diti o n d uri n g  ca ncer  treat me nt. M ost pre vale n ce  esti mates 
ha ve  r a n ge d  bet w ee n  1 0  a n d  2 5 %. [ 8 9] De pressi o n  c o ul d  i ncreas e  s y m pt o m  b ur de n, [ 9 0] affects 
c o g niti o n, [ 9 1] Q O L, [ 9 2] a n d s ur vi val. [ 7 4, 9 3, 9 4] We selecte d t he Patie nt Healt h Q uesti o n naire- 9 
( P H Q-9)  de pressi o n  scale  as  o ur  meas ure  f or  de pressi o n. [ 9 5] T he  P H Q -9  parallels  t he  ni ne 
dia g n ostic s y m pt o m criteria of t he D S M -I V f or M aj or De pressi ve Dis or der ( M D D). T he f or mat a n d 
te m p oral  fr a me w or k  of  t he  ite ms  als o  c orres p o n d  t o  t he  D S M-I V  criteria  a n d  ca n  facilitate  t h e 
f oll o w-u p  re vie w  of  s y m pt o ms  a n d  dia g n ostic  pr ocess.  Wit h  9 -ite ms,  partici pa nts  will  rate  t he 
fre q ue n c y  of  t he  9  s y m pt o ms  o ver  t he  past  2  wee ks  o n  a 4- p oi nt  Li kert  scale  ( 0  =  n ot  at  all,  1  = 
se veral d a ys, 2 = m ore t ha n half of t he da ys, a n d 3 = nearl y e v er y d a y).[ 8 3] T he t otal sc ore of t he 
P H Q -9 ra n ge d fr o m 0 t o 2 7, wit h hi g her sc ores i n dicati n g greater se v erit y of de pressi ve s y m pt o ms. 
T he  i nter nal  r el ia bilit y  was  re p orte d  t o  be  hi g h  ( Cr o n bac h  α  =  . 9 1).  M aj or  de pressi ve  dis or der  is 
dia g n ose d if 5 or m ore of t he 9 de pressi o n s y m pt o ms ha ve b ee n prese nt at least “ m ore t ha n half t h e 
da ys ” i n t he past 2 wee ks a n d if o ne of t he s y m pt o ms is de presse d m o o d or a n he d o nia. O ne of t he 9 -
s y m pt o m criteria (“t h o u g hts t hat y o u w o ul d be better off dea d or of h urti n g y o urs elf i n s o me wa y”) 
c o u nts  as  o ne  of  t he  dia g n ostic  criteria  f or  d e pressi ve  dis or ders  if  pres e nt  at  all,  re gar dless  of 
d urati o n. [ 9 6] Acc or di n g t o t he rec o m me n dati o n of Kr oe n ke et al, [ 9 6] sc ores of 0 t o 4, 5 t o 9, 1 0 t o 
1 4,  1 5  t o  1 9,  a n d  2 0  or  gr eater  are  use d  t o  d efi n e  5  gr o u ps  wit h  i ncreasi n g  se v erit y  of  d e pressi ve 
s y m pt o ms.  At o nl y 9 ite ms, t he P H Q -9 is s h orter t ha n m ost de pressi o n scree ni n g meas ures. U nli ke 
m ost  ot her  meas ures  of  de pressi o n,  t he  P H Q -9  was  de vel o pe d,  teste d  a n d  refi ne d  f or  use  wit h 
me dical patie nts. T his is  i m p orta nt beca us e t he criteri o n vali dit y was esta blis he d i n a p o p ulati o n wit h 
hi g h r ates of ot her p h ysical s y m pt o ms a n d ass oci ate d n o n -s pecific ps yc h ol o gical distress. It h as als o 
de m o nstrate d acce pta bilit y a m o n g n o n -ps yc hi atric patie nts a n d a m o n g b us y pr i mar y care pr o vi ders. 
[ 9 5- 9 7] It  is  se nsiti ve  t o  c ha n ge  a n d  treat me nt  effects, [ 9 8] ma ki n g  it  a  vali d  l o n git u di nal  cli nical 
 
t o ol. 
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2 0 
 
 
 
P h ysical acti vit y as a c o m p o ne nt of t he Frie d Frailt y I n de x is meas ure d b y a s u bscal e of t he Me dical 
O utc o mes St u d y ( M O S) P h ysical H ealt h. T he M O S P h ysi cal H ealt h Scale meas ures a br o a d ra n ge of 
p h ysical f u n cti o ni n g, wit h q uesti o ns ra n gi n g fr o m “ Ca n y o u bat h e a n d dress y o urself? ” t o “ Ca n y o u 
perf or m vi g or o us acti vities, s uc h as r u n ni n g or lifti n g h ea v y o bjects? ” Ite ms are rate d o n a 3 - p oi nt 
Li kert scale m eas uri n g i n de pe n de n ce i n perf or mi n g t he acti vit y. I nter nal c o nsiste nc y of t he p h ysical 
f u ncti o n sc ore is 0. 9 2.[ 9 9] 
 
        
Q O L meas ur es will be assesse d at:  
1)  St u d y e nr oll me nt.  
2)  After a p pr o xi matel y 1 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
3)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
4)  After  a p pr o xi matel y  6  m o nt hs  fr o m  st u d y  e nr oll me nt  a n d,  if  necessar y,  a dj uste d  wit hi n  a 
li mit of 3 0 da ys t o ha v e t his assess me nt d o ne pri or t o treat me nt wit h eit her all o ge nei c H C T 
or a d diti o nal n o n- tra ns pl a nt t hera pies. 
5)  At 3, 6, 1 2, a n d 1 8 m o nt hs after d a y 0 of all o ge n eic H C T f or reci pie nts of H T C or at 9, 1 2, 
1 8, a n d 2 4 m o nt hs fr o m st u d y e nr oll me nt f or patie nt n ot treate d wit h H C T.  
 
8. 1. 1 5  O A R S M ulti di me nsi o n al F u ncti o n al Assess me nt  Q uesti o n n aire ( O M F A Q) :  
 
Eac h patie nt will c o m plete a n assess me nt of his/ her res p ecti ve f u ncti o nal stat us as a meas ure me nt of 
a bilit y  t o  perf or m  acti vities  of  dail y  li vi n g.  A  p orti o n  of  t he  O A R S  M ulti di me nsi o nal  f u ncti o nal 
Assess me nt Q uesti o n naire  ( O M F A Q)  will  be  a d mi nistere d,  as  it  gi ves  a  vie w  of  t he  patie nt’s 
f u ncti o nal  stat us  a n d  i n de pe n de n ce,  i ncl u di n g:  s ocial,  ec o n o mic,  me ntal  a n d  p h ysical  healt h,  a n d 
self-care  ca p acit y.     T he  first  part  i ncl u des  se ve n  q uesti o ns  re gar di n g  t he  i nstr u me ntal  acti vities  of 
dail y  li vi n g  (c o m m uti n g,  c o o ki n g,  s h o p pi n g,  a n d  a bilit y  t o  ha n dl e  fi na nces).    T he  sec o n d  part 
i ncl u des  se ve n  q uesti o ns  re gar di n g  t he  acti vities  of  d ail y  li vi n g  ( bat hi n g,  dressi n g,  t oileti n g, 
wal ki n g).  T h e sc or es ra n ge fr o m 0 t o 2, wit h l o wer sc ores i n dicati n g hi g her le vels of de pe n de n c y o n 
ot hers t o c o m plete t he acti vities.  T he assess me nt is esti mate d t o ta ke 5 mi n utes.  T he O M F A Q will 
be  sc ore d  acc or di n g  t o  t he  rec o m me n d ati o ns  of  t he  de vel o pers.    T h e  meas ures  ha v e  g o o d  vali dit y 
[ 1 0 0].   
 
T hese vari a bles will be assesse d at:  
1)  St u d y e nr oll me nt.  
2)  After a p pr o xi matel y 1 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
3)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y  
c ycle.  
4)  After  a p pr o xi matel y  6  m o nt hs  fr o m  st u d y  e nr oll me nt  a n d,  if  necessar y,  a dj uste d  wit hi n  a 
 
li mit of 3 0 da ys t o ha v e t his assess me nt d o ne pri or t o treat me nt wit h eit her all o ge nei c H C T 
or a d diti o nal n o n- tra ns pl a nt t hera pies. 
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2 1 
5)  At 3, 6, 1 2, a n d 1 8 m o nt hs after d a y 0 of all o ge n eic H C T f or reci pie nts of H T C or at 9, 1 2, 
1 8, a n d 2 4 m o nt hs fr o m st u d y e nr oll me nt f or patie nt n ot treate d wit h H C T. 
 
 
8. 1. 1 6  S atisf acti o n S ur ve ys: 
 
T he patie nt will c o m plet e t w o s atisfacti o n s ur ve ys: Da mia n’s Satisfacti o n wit h Me dical Care Scale 
a n d H ol mes-R o v ner’s Satisfacti o n wit h Treat me nt Scale [ 1 0 1]. 
Satisfacti o n wit h d oct or -patie nt c o m m u nicati o n will be assesse d wit h a s atisfacti o n scale p u blis he d 
b y Da mia n. Se v e n ite ms meas ure d o n 5 p oi nt Li k ert scale (“c o m pletel y dissatisfie d” t o “c o m pletel y 
satisfie d”) a n d s u m me d t o gi ve a t otal satisfacti o n sc ore (ra n ge 5 - 3 5).  F or e x a m ple, ite ms i ncl u d e 
satisfacti o n  wit h  d o ct or’s  e x pla nati o n  of  t he  pati e nt’s  c o n diti o n,  a m o u nt  of  i nf or mati o n  pr o vi de d, 
o p p ort u nit y t o as k q u esti o ns, h o nest y, a n d willi n g ness t o disc uss patie nts’ fears. T his scale detect e d 
differe n ces i n satisfacti o n bet wee n patie nts w h o were or we re n ot pr o vi de d s u m mar y letters of t heir 
c o ns ultati o ns ( 3 2. 5 vs. 3 0, p = 0. 0 1). 
 
T he H ol mes -R o v ner’s 6 ite m Satisfacti o n wit h Decisi o n Scale will be use d t o meas ure satisfacti o n 
wit h treat me nt c h oice. T he scale is writte n at a n 8 t h gra de le v el a n d ta kes a p pr o xi matel y 1 mi n ute t o 
c o m plete. It f oc us es m or e o n act ual satisfacti o n wit h decisi o n t ha n O’ C o n n or’s decisi o nal c o nflict 
scale a n d is c o m para ble t o t he Sai nf ort P ost Decisi o n Satisfacti o n Scale. Si nce pil ot w or k s h o we d 
t hat 4 8 % of 7 3 tra ns pla nt patie nts i n dicate d t he hi g hest le v el of satisfacti o n wit h t heir treat me nt 
decisi o ns o n t he H ol mes- R o v ner satisfacti o n scale, res ults will be dic h ot o mize d i nt o ma xi mall y 
satisfie d vs. less t ha n ma xi mall y satisfie d. Re gret will be meas ure d at 3 m o nt hs wit h t w o ite ms ( wis h 
t o c ha n ge o ne’s mi n d, a n d feeli n g t hat o ne w o ul d be better off a n ot her treat me nt ha d bee n sel ecte d) 
meas ure d o n a 6 - p oi nt Li kert scale refl ecti n g fre q ue nc y of feeli n gs. Cr o n b ac h’s al p h a was 0. 8 0 i n a 
st u d y of 2 0 1 me n wit h pr ostate ca ncer. 
 
T hese vari a bles will be assesse d at:  
1)  St u d y e nr oll me nt.  
2)  After  a p pr o xi matel y 1 m o nt h fr o m st u d y e nr oll me nt a n d  at least 2 8 da ys  fr o m last t hera p y 
c ycle.  
3)  After a p pr o xi matel y 3 m o nt hs fr o m st u d y e nr oll me nt a n d at least 2 8 da ys fr o m last t hera p y 
c ycle.  
4)  After  a p pr o xi mat el y  6  m o nt hs  fr o m  st u d y  e nr oll me nt  a n d,  if  necessar y,  a dj uste d  wit hi n  a 
li mit of 3 0 da ys t o ha v e t his assess me nt d o ne pri or t o treat me nt wit h eit her all o ge nei c H C T 
or a d diti o nal n o n- tra ns pl a nt t hera pies. 
5)  At 3, 6, 1 2, a n d 1 8 m o nt hs after d a y 0 of all o ge n eic  H C T f or reci pie nts of H T C or at 9, 1 2, 
1 8, a n d 2 4 m o nt hs fr o m st u d y e nr oll me nt f or patie nt n ot treate d wit h H C T. 
 
8. 1. 1 7  Fr ailt y  
 
 
Frailt y will be e val u ate d acc or di n g t o t he fi ve crit eria pr o p ose d b y Fri e d, [ 6 7] f oll o wi n g t he ori gi n al 
c ut- off p oi nts, wit h s o me m o dificati o ns [ 1 0 2]: 1) U ni nte nti o nal wei g ht l oss ( S hri n ki n g) of ≥5 % i n t he 
last year. 2) L o w e ner g y ( E x ha usti o n): Base d o n t w o q uesti o ns as ki n g a b o ut i nterest or pleas ure i n 
d oi n g t hi n gs a n d as ki n g a b o ut feeli n g d o w n, de presse d or h o peless. T h ose w h o a ns were d " m ore t ha n 
half of t he da ys" or " n earl y e v er y da y" t o at least o ne of t hese q u esti o ns were c o nsi dere d t o meet t his 
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criteri o n. 3) Wea k n ess: T he Ti me d U p a n d G o is a perf or ma n ce test of p h ysical m o bilit y. T h e test 
meas ur es h o w m a n y sec o n ds it ta kes a n i n di vi d ual t o sta n d u p fr o m a sta n d ar d ar m c hair 
(a p pr o xi mate seat hei g ht of 4 6 c m), wal k a dista nce of 3 m ( 1 0 ft), t ur n, wal k bac k t o t he c h air, a n d 
sit d o w n a gai n. T he test was ori gi nall y re p ort e d b y Mattias et al., a n d s u bs e q ue ntl y m o difie d b y 
P o dsia dl o et al.[ 1 0 3] t o be a ti me d test. I n a p o p ul ati o n of frail, c o m m u nit y- d welli n g ol der a d ults, 
t here was g o o d i nterrat er a n d i ntrarat er relia bilit y (i ntraclass c orrelati o n c o efficie nt = 0. 9 9 f or b ot h). 
T he Ti me d U p a n d G o s c ore c orrelate d t o t he s c ores o n t he Ber g Bala n ce S cale (c orrelati o n 
c oeffi cie nt [ r] = −0. 7 2), gait s pee d (r = −0. 5 5), a n d Bart h el I n de x of A D L ( r = −0. 5 1) [ 1 0 3]. 
G ural ni k et al. [ 7 1] re p orte d gait s pee d as a n i m p orta nt pre dict or of disa bilit y. D urati o n < 7 sec o n ds 
will meet criteria of frail f or wea k ness.  4) Sl o w ness: Calc ulate d after wal ki n g 4 meters, a dj uste d f or 
se x a n d hei g ht, acc or di n g t o Frie d. T he c ut- off p oi nts f or 4 meters w ere esta blis he d as, i n me n: 
hei g ht ≤1 7 3 c m a n d ti me 0. 6 5 m/s; hei g ht > 1. 7 3 c m a n d ti me 0. 7 6 m/s; a n d f or w o me n: hei g ht ≤1. 5 9 
c m a n d ti me 0. 6 5 m/s; a n d hei g ht > 1. 5 9 c m a n d ti me 0. 7 6 m/s. 5) L o w p h ysical acti vit y: will be 
ca pt ure d b y t he M O S P h ysical H ealt h Scale. Patie nts sc ori n g i n t he l o west 2 0 % will be assi g n e d a 
p oi nt f or frail f or p h ysical acti vit y.  
Base d o n t h e a b o ve fi ve criteria, w hi c h i nc or p orat es t w o pe rf or ma nce-bas e d meas ures (ti me d u p -
a n d- g o a n d w al k s pee d o ver 4 meters) a n d t hree s elf-re p ort meas ures (e x ha usti o n, wei g ht l oss, a n d 
p h ysicall y frail), r a n ge of sc ores will be 0- 5; 1-2 i n dicates pre -frail, 3-5 i n dicates frail.  
 
    
FI sc ore  will be ass esse d at:  
1)  St u d y e nr oll me nt.  
2)  After  a p pr o xi matel y  6  m o nt hs  fr o m  st u d y  e nr oll me nt  a n d,  if  necessar y,  a dj uste d  wit hi n  a 
li mit of 3 0 da ys t o ha v e t his assess me nt d o ne pri or t o treat me nt wit h eit her all o ge nei c H C T 
or a d diti o nal n o n- tra ns pl a nt t hera pies. 
3)  At 1 8 m o nt hs after da y 0 of all o ge n eic H C T f or reci pie nts of H T C or 2 4 m o nt hs fr o m st u d y 
e nr oll me nt f or patie nt n ot treate d wit h H C T . 
4)  If n o cli nical a p p oi nt me nts, t he ti mi n g ca n be e x pa n de d t o wit hi n 6 m o nt hs of t he a b o ve ti me 
p oi nts. 
 
8. 1. 1 8  C o g niti o n 
 
T he Bless e d Orie ntati o n -Me m or y - C o n ce ntrati o n (B O M C ) test c o nsists of si x q uesti o ns desi g ne d t o 
scree n f or c o g niti ve i m pair me nt. A sc ore > 1 1 si g nifies c o g niti ve i m pair me nt. T he test -retest 
relia bilit y is hi g h ( S pear ma n ra n k c orrelati o n _ 0. 9 6; P _ 0. 0 0 1) [ 1 0 4]. T he  B O M C has e x celle nt 
vali dit y as a s cree ni n g i ns tr u me nt, c orrel ates hi g hl y wit h cli nicia ns’ rati n gs of de me ntia  se v erit y (r _ 
0. 8 9), pre dicts r es ults fr o m a l o n ger ( 2 6- ite m) m e ntal stat us q uesti o n naire, a n d discri mi nates 
bet wee n p atie nts wit h mil d, m o derate, a n d  s e vere c o g niti ve d eficits [ 1 0 5]. 
T he B O M C has b ee n i m ple me nte d i n t he geriatri c assess me nt f or ol d er ca ncer patie nts i n 
C o o perati ve Gr o u p Cli nical Ca ncer Trials ( C A L G B).[ 6 4] T he B O M C has als o bee n rec o m me n de d 
b y t he I nt er nati o nal S oci et y of Geri atric O nc ol o g y f or e val u ati o n of c o g niti o n i n ol der ca ncer 
patie nts. [ 1 0 6] 
Assess me nt f or c o g niti o n d uri n g st u d y f oll o w u p will be all o we d wit hi n a peri o d of 3 m o nt hs bef ore 
or after t h e c orres p o n di n g ass ess me nt ti me p oi nt i n Ta ble 1. 
 
C o g niti o n will be assesse d o nl y i n p atie nts 6 0 ye ars a n d ol der  at: 
 
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1)  St u d y e nr oll me nt.  
2)  At 6 a n d 1 8 m o nt hs after da y 0 of all o ge nei c H C T f or reci pie nts of H T C or at 1 2 a n d 2 4 
m o nt hs fr o m st u d y e nr oll me nt f or patie nt n ot treat e d wit h H C T.  
 
8. 1. 1 9  Q uesti o ns a b o ut s o me g eri atric pr o ble ms o nl y f or p atie nts 6 0 ye ars a n d ol der 
 
T he q uesti o n naire will as k t he f oll o wi n g q uesti o ns: 
8. 1. 1 9. 1  
Visi o n  
8. 1. 1 9. 2  
Heari n g  
8. 1. 1 9. 3  
Ot her p h ysical pr o ble ms or ill ness  
8. 1. 1 9. 4  
Falls  
 
T hese vari a bles will be assesse d o nce at:  
1)  St u d y e nr oll me nt  
 
8. 1. 2 0  Rec o ver y S ur ve y:  
 
T he rec o ver y s ur v e y will as k t he f oll o wi n g q u esti o ns:  
8. 1. 2 0. 1  
Marital stat us  
8. 1. 2 0. 1. 1  C ha n ge si n ce dia g n osis of A M L  
8. 1. 2 0. 1. 2  C urre nt marital stat us . 
8. 1. 2 0. 2  
W or k stat us 
8. 1. 2 0. 2. 1  C ha n ge si n ce dia g n osis of A M L 
8. 1. 2 0. 2. 2  C urre nt w or k stat us. 
8. 1. 2 0. 3  
Fa mil y i n c o me  
8. 1. 2 0. 3. 1  C ha n ge si n ce dia g n osis of A M L  
8. 1. 2 0. 3. 2  C urre nt i nc o me. 
 
T hese vari a bles will be assesse d o nce at:  
1)  2 4 m o nt hs fr o m st u d y e nr oll me nt. 
 
 
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Pa ge 2 4 of 4 5 
T a ble 1: Ti mi n g of St u d y E v al u ati o ns * 
                              
 
Ti mi n g of assess me nts  
 
 
M o nt hs  
Meas ures  
E nr oll me nt
£ 
1  
3  
6 ¥  
9 ¥  
1 2 ¥  
1 8 ¥  
2 4 ¥  
Patie nt -re p orte d s o ci o-de m o gra p hi c  & 
healt h be ha vi ors s ur v e y 
X  
 
 
 
 
 
 
 
A M L dia g n ostic feat ur es  
X  
 
 
 
 
 
 
 
H C T -CI, c o m or bi dities, a n d la b orat or y 
tests 
X  
 
X  
X  
 
 
 
X  
K P S  
X  
 
X  
X  
X  
X  
X  
X  
P h ysicia n pr efere nce s ur ve ys   
X  
X  
X  
X * *  
 
 
 
 
Patie nt Prefere n ce  S ur v e y  
X  
X  
X  
X * *  
 
 
 
 
A vaila bilit y of d o n or, a n d its t y p e  
X  
X  
 
X  
 
 
 
 
Treat me nt details  
 
X  
X  
X  
X  
X  
X  
X  
A M L res p o nse e val uati o ns  
 
X  
X  
X  
X  
X  
X  
X  
T o xicit y gr a di n g  
 
X  
X  
X  
X  
 
 
X  
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Q O L meas ur es  i n Q uesti o n naire Pac k et 
X  
X  
X  
X  
X  
X  
X  
X  
F u ncti o n meas ur es  ( Wal k Test) 
X  
X  
X  
X  
X  
X  
X  
X  
Ti me d U p -G o test f or FI calc ulati o n  
X  
 
 
X  
 
 
 
X  
C o g niti o n i n ol der patie nts  
X  
 
 
 
 
X  
 
X  
Geriatric pr o ble ms i n ol der patie nts  
X  
 
 
 
 
 
 
 
O utc o mes data  
 
X  
X  
X  
X  
X  
X  
X  
P F T , Bl o o d Tests , Uri n e test ( F H site 
o nl y) 
X  
 
 
 
 
 
 
 
Patie nt -re p orte d Rec o ver y s ur v e y 
 
 
 
 
 
 
 
X  
 
* All dates of assess me nts are r ec o m me n de d d ates t hat c o ul d be a dj uste d ( wit hi n a li mit of 3 0 da ys) t o ta ke i nt o acc o u nt s uita bilit y of patie nts’ cli nical 
stat us a n d reas o n a ble rec o ver y of peri p her al bl o o d c o u nts. 
* * Assess me nt will be d o ne if t he patie nt has n ot u n der g o ne H C T   
£ Assess me nt s h o ul d be d o ne after e nr oll me nt a n d prefera bl y bef ore t he st art of treat me nt. H o w e ver, a grace peri o d of o ne w ee k after t he start of 
treat me nt is all o we d t o c o nse nt t he patie nt a n d i ntr o d uce t he assess me nts. S ur ve ys s h o ul d be c o m plete d b y t he patie nts bas e d o n t heir e x perie nces 
bef ore start of treat me nt a n d t he y s h o ul d be ret ur n e d as s o o n as p ossi ble aft er bei n g c o m plete d.  
¥If a patie nt r ecei ve d a n all o ge n eic H C T, t he n st u d y ass ess me nts will be a dj uste d t o reflect t he d urati o ns of pre -tra ns pla nt a n d 3, 6, 1 2, a n d 1 8 
m o nt hs after da y 0 of H C T. 
 
 
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Fi g ur e 3 : Pr o s p e cti v e o b s er v ati o n al st u d y s c h e m a   
 
 
 
 
Di a g n o s e d wit h A M L  
+ r e c ei v e d i niti al 
t h er a p y 
 
I n d u cti o nt h er a p y 
 
R e -i n d u cti o n or 
c o n s oli d ati ot h er a p y 
 
C o n si d er ati o n 
a n d/ or r ef err al f or 
all o g e n ei c H C T  
All o g e n ei c H C T  
C o n v e nti o n al 
t h er a p y 
 
Cl o s e f oll o w u p  
 
Cl o s e f oll o w u p  
 
H o m e  
 
H o m e  
 
E v al u ati o n s:  
1. S o ci o -d e m o gr a p hi c s  
2. A M L f e at ur e s  
3. C o m or bi diti e s  
4. Q O L s ur v e y s  
5. Pr ef er e n c e s ur v e y s  
 
1. A M L 
r e s p o n
 
1. 
A M L 
r e s p  
M
o n
 
 
 
 
A
s s
 
T
i
 
0  
 
1  
 
3  
 
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Pa ge 2 7 of 4 5 
9. 0  
S T U D Y P R O C E S S  
 
Case Re p ort f or ms ( C R F) : C R Fs will be c ollecte d b y t h e st u d y c o or di n at or at F H C R C a n d at o utsi de ce nters. 
T he c o m p o ne nts of t he C R Fs s h o ul d reflect t he pre vi o usl y des cri be d st u d y e val uati o ns ( Ta ble 1). 
 
T he C R F will g ui de t he c ollecti o n of n o n- patie nt -re p orte d dat a i nt o a n electr o nic data bas e t hr o u g h t he pr o gra m 
R E D Ca p ( Researc h Electr o nic Data Ca pt ure) . T h o u g h it’s n ot p ossi ble t o tra nslate a pa per C R F directl y t o a n 
electr o nic  f or mat  d ue  t o  t he  i n here nt  differ e nces  bet wee n  t he  t w o  me di u ms,  t he  tra nslati o n  fr o m  pa per  t o 
c o m p uter  will  sta y  tr ue  t o  t he  ori gi nal  f or mat  as  m uc h  as  p ossi ble.  T he  R E D Ca p  platf or m  has  a n  e xte nsi ve 
l o g gi n g  feat ure  i n  or der  t o  acc o m m o date  a u dit  trails.    E ver y  d esi g n  c ha n ge,  rec or d  a d diti o n  or  e dit,  a n d  data 
e x p ort  is  a ut o maticall y  l o g ge d  b y  user  wit h  a  date -ti me  sta m p.  T his  l o g  is  searc ha bl e  by  us ers  wit h  t he 
a p pr o priate us er ri g hts t hr o u g h t h e sta n dar d R E D Ca p we b- i nterface.  T h e e ntire l o g f or a pr oject is e x p orta ble t o 
a  C S V  file  at  a n y  ti me  b y  us ers  wit h  t h e  a p pr o priate  user  ri g hts.    R E D Ca p  als o  s u p p orts  t he  o pti o nal  “ Data 
Res ol uti o n  W or kfl o w”  feat ure,  w hic h  e n a bles  users  t o  o pe n  u p  iss ues  f or  eac h  varia ble  a n d  eac h  rec or d 
i n di vi d uall y.  T he y ca n t he n assi g n t he iss ue t o t he a p pr o priate user f or res ol uti o n. Fi nall y, users ha ve t he a bilit y 
t o r u n a h ost of sta n dar d data q ualit y q ueri es (li ke missi n g val ues, o utliers, etc.) i n or d er t o c hec k t he i nte grit y of 
t he  data.  Users  ca n  als o  tail or  c ust o m  data  q ualit y  q ueries  t o  c hec k  s pecific  criteria  rele v a nt  f or  t hat  pr oject.  
T hese q u eries ca n be r u n i n t he sa m e w a y as t h e sta n dar d dat a q ualit y q ueri es or i n real ti me at t he ti me of a 
f or m s u b mittal b y a user. 
  
Data fr o m s o ur ce d o c u me nts will be use d t o tra ns cri be critical pr ot oc ol dat a o n C R Fs. S o urce d oc u me nts are 
d oc u me nts w her e patie nt data ar e rec or de d a n d d o c u me nte d. T he y i ncl u d e, b ut are n ot li mite d t o, cli nical 
s u m maries, la b orat or y res ults, p har mac y dis pe nsi n g rec or ds, a n d pat h ol o g y re p orts. T he o utsi de sit es will se n d 
c o pies of a p pr o priate s o urce d oc u m e nts t o t he C o or di nati n g Ce nter ( F H C R C) f or perf or ma nce of q u alit y 
ass ura nce e val u ati o ns of t he e ntere d d ata. T he ori gi nal d oc u m e nts will be ke pt i n sec ure d b uil di n gs at F H C R C .  
F or eac h patie nt, t he o utsi de sites will als o se n d a har d c o p y of t h e first pa ge of t he C R F, w hic h i ncl u des t he 
PI’s si g nat ur e verif yi n g eac h patie nt’s  eli gi bilit y.  
 
P F T  a n d Bi o mar ker Sa m ple:  At e nr oll me nt, partici pa nts e nr olle d at F H C R C or Seattle Ca ncer Care Allia nce 
S o ut heast La k e U ni o n ( S C C A- S E L U) will be assesse d f or D Lc o a n d F E V 1 .  If t he patie nt has alrea d y bee n 
assesse d f or t h ese tests  as part of his/ her me dical care , t his data will be c ollecte d fr o m t he patie nt’s rec or ds.  T he 
patie nt will als o b e as ke d t o pr o vi de a bl o o d sa m ple, eit her at S C C A -S E L U if see n as a n o ut patie nt or at 
U W M C if see n as i n patie nt, pri or t o start of i nitial t hera p y. Sa m ples will be r o ute d t o Researc h Testi n g Ser vice 
( R T S) at U W M C. T he patie nt will als o be as ke d t o pr o vi de a uri ne s a m ple t o c hec k t he al b u mi n -creati ni ne rati o, 
as well as uri ne a nal ysis.  
 
C o m pleti o n of S ur ve ys : At e nr oll me nt, t he patie nt s ur ve ys will be a d mi nistere d b y t he dat a c o or di n at or i n 
Seattle a n d c olla b orati n g ce nters’ st aff at t he ot her sites. Q uesti o ns raise d b y patie nts a b o ut t he s ur ve ys will be 
a ns wer e d b y t he a d mi nisteri n g st aff. C o ntact i nf or mati o n of t he Seattle data c o or di nat or will be a v aila ble f or 
patie nts e nr olle d at t he o utsi de ce nters t o a ns w er a n y a d diti o nal q uesti o ns a b o ut t he st u d y or t h e s ur ve ys. All 
f oll o w- u p patie nt s ur ve ys will be c ollecte d b y t he data c o or di nat or l ocate d i n Seattle. F or eac h c o m plete d 
s ur ve y, t he patie nt will recei ve $ 2 0 i n re m u n erati o n, f or a t otal ma xi m u m of $ 1 6 0 o ver t w o years. 
 
C ollecti n g/se n di n g  s ur ve ys: T he p atie nt will be as ke d a hea d of ti me a b o ut his/ her preferre d met h o d of 
c o m pleti n g t he s ur v e y: e mail or pe ncil -pa p er  (See  st u d y d oc u me nt ‘ M et h o d of C o m m u nicati o n ’)
 
. T he w e b-
base d q uesti o n naire is pr eferre d b ut t he pe n cil- pa per met h o d will be a vaila ble per patie nt prefere nce. T he 
met h o d use d f or c ollecti o n of s ur ve ys will be r ec or de d f or eac h p atie nt. T hr o u g h t he w e bsite, t he c o or di nat or 
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2 8 
will e mail t he s ur ve y at t he pr o p ose d s ur v e yi n g ti mes  a n d t he partici p a nt ca n t he n fill t he s ur ve y pac ket 
electr o nicall y.  
Patie nts w h o ha ve i nitiall y re q ueste d t he p a per - pe ncil q uesti o n naire will h a ve t he q uesti o n naire m aile d t o t heir 
h o me a d dress wit h pr e pai d ret ur n- e n v el o pes.  O nce a c o m plete d s ur ve y is recei ve d, t h e st u d y c o or di nat or will 
e nter data fr o m t he s ur v e ys i nt o R E D Ca p . T he c o or di nat or will peri o dicall y u p dat e t he s ur vi val/ deat h data t o 
e ns ure t he p atie nt is ali ve pri or t o i nitiati n g t he s ur ve y re mi n ders.  
T he s t u d y c o or di nat or will c o ntact t he patie nt wee kl y aft er se n di n g t he s ur v e y t o e nc o ura ge c o m pleti o n. At eac h 
wee kl y call ( u p t o o ne m o nt h after se n di n g t he s ur ve y), t he patie nt will be offere d t he o pti o n t o fill o ut t he 
s ur ve y o ver t h e p h o ne b y a ns weri n g q uesti o ns fr o m t he st u d y c o or di n at or.  T he st u d y c o or di nat or will t he n 
e nter t he a ns wers i nt o R E D Ca p.  Reas o ns f or i n a bilit y t o c o m plete a s ur ve y pac ket will be c ollecte d a n d 
rec or d e d. St u d y staff will caref ull y re vie w all self -c o m plete d pa per f or ms f or a m bi g u o us res p o nses a n d missi n g 
data, a n d cl arif y t hese wit h t he partici pa nt. T he m et h o d of s ur ve y c ollecti o n will be rec or d e d. 
 
P h ysicia n c o ns e nt a n d assess me nts  will be se nt t o F H C R C p h ysicia ns eit her t hr o u g h R E D C a p, via e mail, or 
i nter-de part me ntal mail . T he sa me met h o ds will be use d b y st u d y c o or di nat ors at o utsi de ce nters t o c ollect 
a ns wers fr o m t heir r es pecti ve p h ysici a ns. F oll o w u p assess me nts will be ha n dle d b y F H C R C st u d y c o or di nat ors 
f or all p h ysicia ns, prefer a bl y usi n g R E D Ca p c o m m u nicati o ns. 
 
Data S ec urit y 
A n y p u blicati o n or prese ntati o n will s u m marize patie nt data a n d n ot refer t o patie nts b y u ni q ue p atie nt n u m ber 
or na me t o ass ur e patie nt c o nfi de ntialit y. T h e lice nse d me dical rec or ds d e p art me nt, affiliate d wit h t he i nstit uti o n 
w here t he p atie nt recei ves me dical care, mai ntai ns all ori gi nal i n patie nt a n d o ut patie nt c hart d oc u me nts. Patie nt 
researc h files are m ai ntai ne d b y a desi g nate d researc h c o or di n at or at eac h i nstit uti o n a n d ke pt i n a l oc ke d r o o m 
wit h access r estricte d t o pers o n nel. A st u d y s pecific data base will als o use t he u ni q ue patie nt n u m ber a n d will 
n ot i ncl u de patie nt na mes. Access t o t he d ata base will be restricte d b y el ectr o nic pass w or d pr otecti o n a n d 
restricte d access t o c o m p uters (i.e., l oc ke d offices). 
R E D Ca p is l ocate d o n t w o ser vers t hat are pr otect e d b y a fire wall.  Eac h i n di vi d ual t hat nee ds t o access 
R E D Ca p (t hat is, t he st u d y c o or di nat ors a n d i n vesti gat ors) h as his/ her o w n acc o u nt.  R E D Ca p i m ple me nts 
a ut he nticati o n t o vali date t he i de ntit y of e n d- users t hat l o g i n t o t he s yst e m.  Eac h acc o u nt ca n o nl y h a ve access 
t o pr ojects i n R E D Ca p t hat t he pers o n has b ee n i n vite d t o.  T he F H C R C St u d y C o or di nat or will deter mi ne 
w hic h part of t he pr oject ot her users ha v e access t o.   R E D Ca p utilizes a n a ut o -l o g o ut setti n g, w hic h is 
c ust o miza ble ( defa ult a ut o-l o g o ut ti me is 3 0 mi n utes), a n d will a ut o maticall y l o g a us er o ut of t he s yste m if 
he/s he has n ot ha d a n y acti vit y ( e. g. clic ki n g, t y pi n g, m o vi n g t he m o use) o n his/ her c urre nt we b pa ge f or t he set 
a m o u nt of ti me.  T his pre ve nts s o me o ne else fr o m accessi n g t he acc o u nt a n d pr oject data if a w or kst ati o n is left 
wit h o ut pr o perl y l o g gi n g o ut or cl osi n g t he br o ws er wi n d o w.  T o hel p pr otect a n d sec ure t h e data st ore d i n 
R E D Ca p’s bac k - e n d data base, t he s oft w are a p plicati o n e m pl o ys vari o us met h o ds t o pr otect a gai nst malici o us 
users w h o ma y atte m pt t o i de ntif y a n d e x pl oit. 
 
St u d y Partici pa nt C o m mittee:  
A n u m ber of 1 2 st u d y partici pa nts will be i n vite d t o j oi n t he st u d y sta k e h ol ders. T w o partici pa nt-sta ke h ol ders 
will be selecte d r a n d o ml y fr o m eac h site a n d will be i n v ol ve d i n researc h disc ussi o ns. We will use a ra n d o m 
n u m ber ge nerat or (f o u n d at w w w.r a n d o m n u m ber ge n erat or.c o m ) t o select t w o n u m bers bet wee n 1 a n d 1 0 0 
 
w hic h will c oi nci de wit h partici pa nts’ u ni q ue st u d y- relate d I D. We will ge nerate n e w n u m bers f or eac h site. 
T hese t w o partici p a nts will be c o ntacte d via tele p h o ne a n d will be pr o vi de d wit h a n e x pla nati o n a b o ut t he st u d y 
o bjecti ves a n d r ole of sta ke h ol ders. If t h e partici p a nt decli nes partici pati o n as a sta ke h ol der, we will use t he 
we bsite t o select a n e w n u m ber u ntil we ha ve t w o partici pa nt-sta ke h ol d ers fr o m eac h site. O ur g oal is t o 
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re pres e nt all fi ve sites, b ot h ge n d ers, vari o us a ge i nter vals ab o ve 6 0 years ol d, a n d varia ble b ur de ns of 
c o m or bi dities .  
 
T he c o nstr ucti o n of t his c o m mittee prefer a bl y t o  be c o m plete d wit hi n t he first year of t h e st u d y e nr oll me nt.  
 
T he st u d y p artici pa nt c o m mittee me m bers will be as ke d t o e val uat e o ur met h o ds i n tra nslati n g ke y r es ults i nt o 
la n g u a ge t hat ca n be c o m m u nicate d t o ot her partici pati o ns, i n or der t o i m pr o ve partici pati o n a n d mi ni mize 
l osses t o f oll o w- u p, a n d t o f ut ure patie nts, t o e ns ure br oa d disse mi nati o n of res ults.  
 
C o m pleti o n of E x pert O pi ni o n S ur ve ys :  
U p o n s u b missi o n of t he c o m plete d s ur ve y, partici p ati n g p h ysicia ns will be e ntere d i n a dra wi n g t o wi n o ne of 
t we nt y $ 5 0. 0 0 A m az o n gift car ds. Wi n ners will be ra n d o ml y selecte d a n d n otifie d b y e m ail.  
 
1 0. 0  
A D V E R S E E V E N T S  
 
Si nce t he pr o p ose d st u dies are n ot tr eat me nt pr ot o c ols, t here will be n o ris ks i n a d diti o n t o t h ose e x plai ne d t o 
t he patie nts as parts of t h eir treat me nts f or A M L. 
 
T here is a ris k of breac h of c o nfi de ntialit y. We ha ve ta ke n all p ossi ble meas ures t o a v oi d t his ris k. We will 
e x plai n t o patie nts t his ris k i n t he c o nse nt f or m a n d we will ass ure t he m a b o ut o ur met h o ds t o pr otect t heir 
c o nfi de ntialit y.  
 
Ps yc h ol o gical a n d s o cial stress mi g ht be ass o ciate d wit h i nf or mi n g t he pati e nts of t heir c o m or bi dit y sc ores a n d 
h o w t hese mi g ht i m pact t heir treat me nt o utc o mes. Eac h patie nt has a s pecifie d fa mil y m e m ber, g u ar dia n, or 
frie n d ( de p e n di n g o n t he a ge of patie nt) w h o pr o vi des s u p p ort f or patie nts d uri n g a n d after t he s ur ve y. P ote ntial 
ps yc h ol o gical stress i ncl u des k n o wle d ge of tra ns pla nt relate d c o m plicati o ns a n d fear of treat me nt fail ure, 
c hr o nic ill ness, a n d p ote ntial deat h. Eac h tr eat me nt ce nter h as trai ne d ps yc h ol o gists, ps yc hiatrists, a n d s ocial 
w or kers a vaila ble f or patie nts a n d t heir fa milies.  
 
P F T c o ul d carr y t he ris k of t he patie nts de vel o pi n g c o u g h or feeli n g li g ht- h ea de d or dizz y. It ca n als o ca use a 
feeli n g of pr ess ure i n t he c hest, bell y, or hea d. T hese tests are d o n e i n cli nical facilities a n d p h ysicia ns are 
availa ble t o deal wit h a n y sit uati o n res ulti n g fr o m t hese tests.  
 
T here is a rar e ris k of blee di n g d uri n g c ollecti o n of researc h s a m ples. It is rare beca us e we will c ollect t hese 
sa m ples o nl y at b aseli ne bef ore t h e patie nt has recei ve d a n y c h e m ot hera p y t hat mi g ht res ult i n l o weri n g t heir 
platelet c o u nts.  
 
Per I R B r ul es, o nl y relate d, u ne x pecte d, a n d seri o us a d verse e ve nts will be r e p orte d t o t he a p pr o priat e I R B, 
wit hi n te n ( 1 0) cale n d ar da ys of bec o mi n g a ware of t he e ve nt.  
 
1 0. 1  
Re p orti n g Seri o us a n d U ne x pecte d A d verse E v e nts ( S A E) fr o m P a rtici p ati n g Sites  
All u na ntici pate d seri o us a d verse e ve nts t hat are c o nsi dere d rel ate d t o st u d y partici pati o n m ust be 
re p orte d t o t he F H C R C I n vesti gat or wit hi n 7 2 h o urs of lear ni n g of t he e ve nt. T he i m me diate 
tele p h o ne re p ort m ust be f oll o we d b y a re p ort fa x e d t o t he F H C R C St u d y C o or di nat or at 2 0 6- 6 6 7-
2 3 0 3. A n y f oll o w- u p i nf or mati o n m ust be s u b mitte d as s o o n as t he rele va nt i nf or mati o n is a vaila ble.  
 
 
 
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1 1. 0  
S T A TI S TI C A L C O N SI D E R A TI O N S  
 
1 1. 1  
I ntr o d ucti o n a n d s a m ple size 
 
T o i m pr o ve t he stre n gt h of t he fi n di n gs as well as re p orti n g of t hese fi n di n gs, we will f oll o w t he 
rec o m me n dati o ns of S T R O B E State me nt (see st u d y d oc u m e nt ‘ ST R O B E  Criteria’ ) w hic h pr o vi des g ui deli nes 
of h o w t o disc uss a n d re p ort st u d y desi g n, a n al ysis, a n d fi n di n gs i n ma n us cri pt writi n g.  
 
T here is n o tar gete d n u m ber f or e nr oll me nt o n t his st u d y. I nstea d, we pla n t o e nr oll all eli gi ble p atie nts 
c o nti n u o usl y f or d u rati o n of 3 6- 4 0 m o nt hs fr o m st u d y acti vati o n. We a ntici pate e nr olli n g a p pr o xi matel y 1 0 0 0 
patie nts fr o m all sites b ut we will all o w e nr oll me nt of m ore patie nts if e nr oll me nt rates were u ne x pecte dl y 
hi g her. 
 
Base d o n a pr eli mi nar y s cree n of t he S C C A rec or ds o ver years 
2 0 0 8- 2 0 0 9, a p pr o xi matel y 1 8 0, 1 2 5, 1 2 0, a n d 7 5 eli gi ble 
patie nts wit h A M L w ere see n a n n uall y at t he 4 c olla b orati n g 
i nstit uti o ns, res pecti vel y, f or a n a n n u al t otal of 5 0 0 patie nts.   We 
a ntici pate e nr oll me nt r ate of a p pr o xi matel y ~ 6 5 % res ulti n g i n a 
t otal of a p pr o xi matel y 1 0 0 0 patie nts o bser ve d o ver 3 years. 
Base d o n a pr eli mi nar y s cree n, we a ntici p ate t hat 5 0 % ( n = 5 0 0) 
will be ≥6 0 years of a ge. A m o n g t he re mai ni n g 5 0 0 y o u n g er 
patie nts, we w o ul d a ntici pate ( bas e d o n hist orical distri b uti o n of c o m or bi dit y sc ores a m o n g H C T reci pie nts) 
t hat a p pr o xi matel y 3 5 % ( n = 1 7 0) will ha ve si g nifi ca nt c o m or bi dities (sc ores of ≥3). T his s u g gests t hat t he 
c o m bi ne d c o h ort of ol der or me dicall y i nfir m patie nts eli gi ble f or st u d yi n g t he rate of recei vi n g all o ge neic H C T 
will be a p pr o xi matel y 6 7 0 patie nts o ver 3 years. T a ble 2  s h o ws a n esti mate of t he mi ni mal i ncre me nt i n 
i nci de nce of H C T detect a ble wit h 8 0 % p o wer at t he 2-si de d 0. 0 5 le vel of si g nifica n ce, f or var yi n g ass u m pti o ns 
a b o ut t he pre val e nce of t he ris k fact or.  T hese esti mates ass u me a ti me -t o-e ve nt a nal ysis, 2 5 % o verall i nci de nce 
at 2 years p ost- i nitial t her a p y a n d 2 5 % i nci de n ce of deat h wit h o ut H C T as a c o m peti n g ris k.   
 
F or t he c o m paris o n st u d y, p o wer calc ulati o ns are c o m plicate d b y t h e ti me- d e pe n de nt nat ure of t he 
treat me nt gr o u ps, as w ell as b y li kel y n o n- pr o p orti o nalit y i n t he hazar d rati o f or H C T.  Were t hes e fact ors n ot 
prese nt, t he e x pecte d 1 7 0 patie nts u n der g oi n g H C T c o m pare d t o 5 0 5 w h o d o n ot u n der g o H C T, w o ul d pr o vi de 
at least 8 0 % p o wer t o det ect a n i ncr eas e i n O S of 1 3 %, at t he 2-si de d 0. 0 5 le vel of si g nifi ca nce.  Beca use of t h e 
lar ge n u m ber of u n k n o w n ass u m pti o ns it is nearl y i m p ossi ble t o esti mate t he tr ue p o wer f or t h e act u al a nal ysis 
t hat will be d o ne, ot her t ha n t hat t he detect a ble effect size is li kel y c o nsi dera bl y l ar ger t ha n 1 3 %.  N e vert heless, 
base d o n pre vi o us e x perie nce wit h ti me- de p e n de nt a nal ys es (s uc h as of c hr o nic graft -v ers us -h ost dis ease after 
H C T), [ 1 0 7] t he o verall sa m ple size s h o ul d be s ufficie nt t o detect effects of mea ni n gf ul cli nical ma g nit u de.  
 
 
1 1. 2  
T he pr o b a bilit y a n d pre dicti ve f act ors f or u n der g oi n g all o ge neic H C T  
 
( 1) Base d o n sa m ple size calc ulati o ns (see S a m ple Size secti o n) , we a ntici pate t otal sa m ple of 1 0 0 0 patie nts 
c o ntri b uti n g t o t his a nal ysis. Patie nts of ≥6 0 years will be ~ 5 0 0 w hile t h ose < 6 0 years will be ~ 5 0 0 p atie nts. 
A m o n g y o u n ger patie nts: we a ntici pate 4 0 % ( n = 1 7 0) will ha ve hi g h c o m or bi dit y s c ores.  T h e c o h ort of 
c o m bi ne d ol der or me di call y i nfir m patie nts eli gi ble f or st u d yi n g t he rate of recei vi n g all o ge n eic H C T will be 
a p pr o xi matel y 6 7 0 patie nts. 
( 2) T he r ate of u n d er g oi n g all o ge n eic H C T will be esti mate d f or t he w h ole o bser ve d p o p ulati o n, c o m pari n g 
ol der/ me dicall y i nfir m patie nts t o all ot her patie nts.  
T a bl e 2 : P o w er C al c ul ati o n f or S p e cifi c Ai m #2  
Pr e v al e n c e of  
ri s k f a ct or or gr o u p 
I n cr e m e nt i n H C T 
i n ci d e n c e ( H R) 
1 0 %  
0 . 17  (1. 9 ) 
2 0 %  
0 .1 3  ( 1. 7) 
3 0 %  
0 .1 1  ( 1. 6) 
4 0 %  
0 .1 0  ( 1. 6) 
 
 
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( 3) Data fr o m patie nts’ preferre d l e vel of i n v ol ve me nt i n treat me nt decisi o n -ma ki n g will be a nal yz e d b y 
assessi n g t he o v er all distri b uti o n of t he m ost fre q ue nt a ns wers a m o n g patie nts w h o recei ve d H C T v ers us 
c o n ve nti o nal t hera p y, usi n g c hi-s q u are d test. C o m paris o ns of pr o p orti o n of patie nts assi g ni n g a p arti c ular 
a ns wer as m ost i m p orta nt will als o be d o ne usi n g c hi-s q uare d t est. T he wei g hte d K a p pa- st atistic will be use d t o 
assess t he le vel of a gree me nt or disa gree m e nt bet wee n t he p atie nt's a n d p h ysicia n’s res p o nses. M ar gi nal C o x 
m o del will be use d t o acc o u nt f or p ote ntial c orrelati o n bet w ee n p h ysicia n a n d patie nt prefere n ces. [ 1 0 8]  
( 4) Diff ere n ces i n Q O L s c ores bet w ee n b aseli ne a n d p ost -treat me nt assess me nts f or eac h patie nt will be teste d 
i n a n a nal ysis of vari a nce ( A N O V A) m o del.[ 1 0 9]  
( 5) T o i de ntif y i n de pe n d e nt pre dicti ve f act ors f or t he feasi bilit y of all o ge neic H C T, m ulti variate C o x 
pr o p orti o nal- hazar ds r e gr essi o n m o dels will be use d, treati n g H C T as t he e v e nt of i nterest a n d d eat h wit h o ut 
H C T as a c o m peti n g ris k. A ss ociati o ns bet wee n t h e p ote ntial pre dicti ve v aria bles, descri be d u n d er Met h o ds, 
a n d t he i nci de nce of all o ge n eic H C T will be e v al uate d usi n g a bac k war d ste p wise a p pr o ac h. V aria bles t hat are 
si g nifica ntl y ass o ciate d wit h eac h o utc o me e ve nt ( P < . 0 5) will be i ncl u de d as c o vari ate fact ors i n t he 
s u bse q ue nt c o m paris o ns. Ti me- de pe n d e nt c o vari ates f or m ulti ple p ost-e x p os ure t hera pi es will be e m pl o ye d 
usi n g pre vi o usl y des cri be d met h o ds.[ 1 1 0] Res ults will be e x presse d as H R f or eac h o utc o me.  
 
1 1. 3  
C o m p aris o n  of  o utc o mes  a m o n g  ol der  a n d  me dic all y  i nfir m  A M L  p atie nts  gi ve n  all o ge neic 
H C T vers us c o n ve nti o n al t her a p y 
 
 
( 1) Ol der a n d me dicall y i nfir m patie nts w h o were pr os pecti vel y e nr olle d f or 2- years u n der S A 2  a n d w h o 
c o m plete d i nitial i nte nsi ve t hera p y will t he n r e pres e nt a c o h ort of p atie nts eli gi ble t o recei ve all o ge neic H C T or 
a d diti o nal c o n ve nti o nal t hera p y ( n = 6 7 0). Bas e d o n preli mi nar y scree n of d ata bases of c olla b orati n g ce nters, w e 
esti mate t hat a p pr o xi matel y 2 5 % of t he 6 7 0 patie nts will u n der g o H C T wit hi n t he ti me fra me of t he st u d y. 
Patie nts w h o d o or d o n ot u n der g o H C T will be c o m pare d f or N R M, O S, D F S, t o xicities, Q O L, f u ncti o n, 
utilizati o n a n d satisfacti o n wit h care. S ur vi v ors at 3, 6, a n d 9 m o nt hs will be c o m pare d f or t hes e t w o o utc o mes. 
( 2) Pri m a r y O utc o mes : (i) Pr o p orti o nal hazar ds re gressi o n m o dels f or t he s u b- distri b uti o ns of c o m peti n g 
ris ks[ 1 1 1] will be use d t o e val uate i m pact of H C T a n d ot her fact ors o n ti me-t o-e ve nt o utc o mes ( N R M, O S, a n d 
D F S).  Si nce H C T ma y b e recei ve d w ell after c o m pleti o n of i n d ucti o n a n d c o ns oli dati o n t hera p y, it will be 
a nal yze d as a ti me -de p e n de nt c o variat e, [ 1 1 0]s o t hat t he c o m paris o n is base d o n patie nts w h o ha ve s ur vi ve d f or 
c o m para ble l e n gt hs of ti me. Si milarl y, p atie nts w h o are n ot ne wl y dia g n os e d at e nr oll me nt will be ha n dle d via 
left tr u ncati o n – i.e., t he y will e nter t he set of patie nts at ris k base d o n ti me si nce dia g n osis. T his a nal ysis will 
be a dj uste d f or t he ris k-stratificati o n m o del, i ncl u di n g c o m or bi dities, diseas e res p o nse, a ge, a n d ot her varia bles; 
pre -e x p os ure Q O L sc or es; s oci o- de m o gra p hic v aria bles, i ncl u di n g dri vi n g ti me t o treati n g ce nters, i nc o me, 
marital stat us, a n d ot her varia bles; ra n ks of patie nt a n d p h ysicia n s ur ve ys of decisi o n- ma ki n g st yl e a n d 
treat me nt val ues; a n d t he i nstit uti o n w here t he patie nt was treate d.  T he e val uati o n of H C T as a ris k fact or ma y 
be c o m plicate d b y t he li k el y n o n - pr o p orti o nalit y of hazar ds.  I n t he s h ort-ter m i nter val after H C T t he ris k of 
deat h ma y i ncr ease relati ve t o t h ose ali ve b ut n ot tra ns pla nte d, t he n d ecli ne d ue t o decrease d rela ps e.  We will 
assess t his p ossi bilit y b y all o wi n g t he h azar d rati o f or H C T t o var y b y ti me after tra ns pla nt i n a ti me - de pe n de nt 
ma n ner.  All P  val ues will be base d o n li keli h o o d rati o statistics  a n d will be 2-si de d. M ulti variate P  v al ues f or a 
varia ble will reflect  a dj ust me nt f or all ot her varia bles i n t he m o del. Meas ures of precisi o n f or t he H R or ris k 
differe n ces will be pr o vi de d i n f or m of c o nfi de nce i nter vals.  
 
(ii)
 
 La n d mar k a nal yses f or all patie nts ali ve at 3, 6, a n d 9 m o nt hs p ost-i n d ucti o n, base d o n pri or hist or y 
of H C T, will be use d t o partial l y c o m pe nsate f or t he ti me- de pe n d e nt nat ure of t he i nter ve nti o n a n d earl y d eat h. 
A p ossi ble a p pr oac h t o descri be t he eff ect of H C T o n o utc o me will be t o di vi de t he ti me a xis i nt o s h ort i nter vals 
(f or e x a m ple, 3- 6 m o nt hs) a n d t o esti mate t he act ual hazar d of t he e ve nt of i nterest d uri n g t he i nter v al i n 3 
differe nt stat es: n ot tra ns pla nte d, earl y after tr a ns pla nt, late after tra ns pla nt.  T his will be base d o n a si m ple 
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e x p o ne ntial ass u m pti o n: i.e., t he n u m ber of e ve nts i n eac h state di vi de d b y t he n u m ber of p e rs o n-years at ris k i n 
eac h state. T hese h azar d rates w o ul d yiel d esti mat es of O S pr o ba bilities, w hic h c o ul d t he n be c o m bi ne d t o yiel d 
esti mates of O S pr o ba bilit y o ver l o n ger i nter v als, f or e x a m ple 1 or 2 years. T he usef ul ness of s u c h esti mates 
w o ul d de pe n d o n r elati ve sta bilit y of t he hazar d rates as a f u ncti o n of ti me si nce i nitial t hera p y. 
 
(iii) Gi ve n t he e x pecte d bias i n treat me nt selecti o n a n d t o f urt her e n ha nce o ur a bilit y of o btai ni n g 
acc urate statistical i nfere nces, we will use pr o pe nsit y s c ores. Pr o p e nsit y s c ores will esti mate t he pr o ba bilit y o n 
t he basis of all patie nts a n d ce nter c har acteristics t hat patie nts w o ul d pr ocee d t o all o ge neic H C T wit h t he use of 
pr o p orti o nal hazar d m o d el t o a dj ust f or bet wee n- gr o u p differe nces i n t he pre vi o usl y me nti o ne d 
c haracteristics. [ 1 1 2] T he ma g nit u de of di v er ge n ce of pr o pe nsit y sc ores bet wee n t he t w o a p pr oac hes will all o w 
us t o assess t he a m o u nt of bias i n treat me nt selecti o n. I n v erse- pr o ba bilit y- wei g hti n g bas e d o n t he pr o pe nsit y 
sc ore will t he n be use d as a sec o n dar y t o ol t o a dj ust f or differe nces bet wee n t he t w o treat me nt- gr o u ps [ 1 1 3]. 
T his a p pr oac h will be i m ple me nte d t o create bal a nce a n d it i n v ol ves wei g hti n g eac h patie nt w h o recei ve d H C T 
b y t he i n verse of t he pr o ba bilit y t hat he or s h e w o ul d be selecte d f or H C T a n d wei g hti n g eac h patie nt w h o 
recei v e d c o n ve nti o nal tr eat me nt b y t he i n v erse of t he pr o ba bilit y t hat h e or s he w o ul d be selecte d f or 
c o n ve nti o nal treat me nt. We will verif y t he p erf or ma nce of t he pr o pe nsit y m o del b y c o m p ari n g t he distri b uti o n 
of c o vari ates a n d pr o p e nsit y s c ores b et wee n treat me nt gr o u ps b ot h bef ore a n d after i n verse pr o ba bilit y 
wei g hti n g. [ 1 1 4] A dj uste d O S c ur ves will be esti mate d usi n g t he i n verse- pr o ba bilit y- w ei g hti n g a p pr oac h of C ole 
a n d Her n a n. [ 1 1 5] Assess me nt of be nefit of eit her a p pr oac h will be d o ne i n q ui ntiles of pr o pe nsit y sc ores. 
 
(i v) Se nsiti vit y a nal yses will be perf or me d t o b etter u n dersta n d a n y statistical disa gree me nt bet w ee n t he 
m o dels. First, O S c ur ves f or c o m pari n g b ot h gr o u ps will be esti mate d usi n g a d o u bl e r o b ust strate g y of 
c o m bi ni n g t he i n vers e- pr o ba bilit y wei g hti n g wit h t he re gressi o n -base d esti mati o n [ 1 1 6]. Sec o n dl y, pr o pe nsit y 
sc ores will be use d t o c o nstr uct matc he d sa m ples fr o m b ot h gr o u ps t o be use d f or si m ple matc he d p air a nal yses 
w hic h a dj ust f or c o nf o u n di n g vari a bles. Fi n all y, w e will use t he met h o d of Li n et al [ 1 1 7] t o assess w het her t he 
o bser ve d diff ere n ces i n t he rate of deat h c o ul d be d ue t o a n u n meas ure d c o nf o u n der.   
( 3) Sec o n d ar y O utc o mes : (i) T he r elati o ns hi p bet wee n t he c h oice of treat me nt ( H C T vs. n o n- H C T) a n d Q O L, 
f u ncti o n, utilizati o n, a n d satisfacti o n sc ores will be e x a mi ne d. I ntra-p atie nt differe n ces will be use d t o a nal yze 
c ha n ges i n Q O L fr o m baseli ne t o f oll o w- u p assess me nts. Basi c a n al ys es will utilize paire d t -tests (f or c ha n ges 
o ver ti me) a n d t w o- s a m ple t-tests (f or c o m p aris o n bet wee n gr o u ps). I n or d er t o ma ke f ull use of t he l o n git u di nal 
data we will als o use ge n eralize d esti mati n g e q u ati o ns ( G E Es) a p pr o ac h, [ 1 1 8] w hic h ca n acc o m m o date t he 
wit hi n patie nt c orrelati o n str uct ure a n d ar bitrar y p atter ns of missi n g dat a. F urt her, t he G E Es a p pr oac h w o ul d 
all o w f or t he p o p ulati o n- a vera ge i nterpr etati o n w hic h is a n a d va nta ge o ver, f or e x a m ple, ge neralize d li near 
mi x e d m o dels a p pr oac h.  
(ii) T he pre vi o usl y des cri be d statistical a p pr oac hes will be use d t o a dj ust t he c o m paris o ns bet wee n reci pie nts of 
all o ge n eic H C T a n d c o n ve nti o nal t hera p y f or t he pre -e x p os ure meas ures of Q O L a n d prefere n ce sc ores.  
(iii) We will c o m pare t he q ualit y -a dj uste d o ut c o mes usi n g t he Q- T Wi S T met h o d ol o g y w hic h wei g hts s ur vi val 
ti me acc or di n g t o cli nical stat us (ali ve wit h o ut rela pse or t o xicit y, rela pse, a n d t o xicit y) [ 1 1 9- 1 2 2] 
( 4) Terti a r y O utc o mes : (i) T he  ris k f act ors f or m ortalit y after I C U a d missi o n i n patie nts wit h A M L will be 
e x a mi ne d. S ur vi val a nal ysis wit h l o gistic re gressi o n or C o x pr o p orti o nal hazar ds m o del will be use d, de pe n di n g 
o n c o m plete ness of patie nt f oll o w- u p. Varia bles i n t he m o del will i ncl u de t he A M L-c o m or bi dit y m o del sc ore, 
hist or y of H C T, A M L disease stat us, a bs ol ute ne utr o p hil c o u nt, use of life s u p p ort de vices, bactere mia, a n d 
creati ni ne. T h e a b o ve ris k fact ors will be e v al uate d u si n g A U C a n d c-statistic t o i nf or m de vel o p me nt of a 
p ote ntial m o del t o pre dict I C U m ortalit y. (ii) T he o utc o mes of patie nts wit h sec o n dar y A M L will be e val uat e d 
as c o m par e d t o patie nts wit h pri mar y A M L, after a dj usti n g f or p erce nt blasts i n t he peri p heral bl o o d, w hite 
bl o o d cell c o u nt, a n d perf or ma nce stat us at ti me of prese ntati o n. 
 
 
1 1. 4  
Missi n g D at a 
 
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T his s pecific ai m de p e n ds o n a hi g h r es p o nse rate fr o m patie nts i n pr o vi di n g dat a. T he PI t o get her wit h t he 
S C C A data c o or di nat or will m o nit or c o m plia nce wit h t he self -re p orte d dat a o n a m o nt hl y b asis a n d i nstit ute 
c orrecti ve meas ures if t h e res p o nse rate f alls bel o w 7 5 %. T hese m a y i ncl u de cl oser trac ki n g of p atie nts t o ma ke 
s ure cli nicall y si g nifica nt ti me p oi nts are rec o g niz e d a n d e v al uati o n of fact ors ass ociate d wit h n o-res p o nse i n 
or der t o i de ntif y p o p ulati o ns w hic h re q uir e greater eff orts. U p o n recei pt of patie nt-re p ort e d data, c o m pleti o n of 
i n di vi d ual ite ms will be assesse d i m me diatel y, s o t hat missi n g data ca n be re q ueste d.  
T he li near mi x e d m o dels a nal ysis  will be a ble t o acc o m m o date ar bitrar y p atter ns of missi n g data; 
h o we ver, gra p hical prese ntati o ns a n d l o gistic re gressi o n a nal ysis will be perf or me d t o u n dersta n d t he missi n g 
data mec h a nis m as well as t o i de ntif y fact ors ass ociate d wit h i nc o m plete dat a f or  s ur vi v ors. Pl ots of c ha n ge i n 
Q O L sc or es fr o m bas eli ne t o 9 0 da ys, 6 m o nt hs, 1- year, a n d 2- year stratifie d b y ti me of dr o p -o ut will be 
ge n erat e d se paratel y f or eac h gr o u p t o d eter mi ne patter n of missi n g d ata.  L o gistic re gressi o n will be use d t o 
i de ntif y bas eli ne a n d cli nical c har acteristics ass oci ate d wit h missi n g data. All de m o gra p hi cs a n d bas eli ne 
c haracteristics will be i ncl u de d i n t he l o gistic m o del.  
 
 
 
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Ref ere nces  
 
 
 
  
 1.   Leit h C P, C hir B, K o pec k y K J, G o d wi n J, Mc C o n nell T, Sl o v a k M L, C he n I - M, He a d D R, 
A p pel b a u m F R, Will m a n C L.  Ac ute m yel oi d le u ke mi a i n t he el derl y: assess me nt of 
m ulti dr u g resist a nce ( M D R 1) a n d c yt o ge netics disti n g uis hes bi ol o gic s u b gr o u ps wit h 
re m ar k a bl y disti nct res p o nses t o st a n d ar d c he m ot her a p y. A S o ut h w est O nc ol o g y Gr o u p 
St u d y.  Bl o o d 8 9: 3 3 2 3- 3 3 2 9, 1 9 9 7. 
  
 2.   Leit h C P, K o pec k y K J, C he n I - M, Eij de ms L, Sl o v a k M L, Mc C o nell T S, He a d D R, Weic k J, 
Gre ver M R, A p pel b a u m F R, Will m a n C L.  Fre q ue nc y a n d cli nic al si g nific a nce of t he 
e x pressi o n of t he m ulti dr u g resist a nce pr otei ns M D R 1/ P - gl yc o pr otei n, M R P 1, a n d L R P 
i n ac ute m y el oi d le u ke mi a. a S o ut h w est O nc ol o g y Gr o u p st u d y.  Bl o o d 9 4: 1 0 8 6- 1 0 9 9, 
1 9 9 9. 
  
 3.   A p pel b a u m F R, G u n d ac ker H, He a d D R, Sl o v a k M L, Will m a n C L, G o d wi n J E, A n ders o n J E, 
Peters d orf S H.  A ge a n d ac ute m yel oi d le u ke mi a.  Bl o o d 1 0 7: 3 4 8 1- 3 4 8 5, 2 0 0 6. 
  
 4.   Fri e d L P, B a n dee n - R oc he K, K as per J D, G ur al ni k J M.  Ass oci ati o n of c o m or bi dit y wit h 
dis a bilit y i n ol der w o me n: t he W o me n's He alt h a n d A gi n g St u d y.  J Cli n E pi de mi ol 5 2: 
2 7- 3 7, 1 9 9 9. 
  
 5.   Y a nci k R, Wesle y M N, Ries L A G, H a vli k R J, L o n g S, E d w ar ds B K, Y ates J W.  C o m o r bi dit y 
a n d a ge as pre dict ors of ris k f or e arl y m o rt alit y of m ale a n d fe m ale c ol o n c arci n o m a 
p atie nts.  C a ncer 8 2: 2 1 2 3- 2 1 3 4, 1 9 9 8. 
  
 6.   S orr or M L, Gir alt S, S a n d m aier B M, de Li m a M,  S h a hj a h a n M, M al o ne y D G, D ee g H J, 
A p pel b a u m F R, St orer B, St or b R.  He m at o p oietic cell tr a ns pl a nt ati o n- s pecific 
c o m or bi dit y i n de x as a n o utc o me pre dict o r f or p atie nts wit h ac ute m y el oi d le u ke mi a i n 
first re missi o n: C o m bi ne d F H C R C a n d M D A C C e x perie nces.  Bl o o d 1 1 0: 4 6 0 8- 4 6 1 3, 
2 0 0 7.  P M CI D: P M C 2 2 3 4 7 8 8 
  
 7.   S orr or M L, St orer B, S a n d m aier B M, M al o ne y D G, Fr a n ke G, S hiz ur u J, C h a u nce y T, A g ur a E, 
M azi arz R T, S a he bi F, L a n gst o n A A, W a de J C, M aris M, Br u n o B, Ye a ger A M, 
P ulsi p her M, Pet erse n F, Bet h g e W A, Mc S w ee ne y P A, Nie der wieser D, Bl u me K G, St o r b 
R F.  All o ge neic he m at o p oietic cell tr a ns pl a nt ati o n ( H C T) after n o n m y el o a bl ati ve 
c o n diti o ni n g f or p atie nts ( pts) a ge d > or = t o 6 0 ye ars. Bl o o d  1 1 2: 7 5 3- 7 5 4, # 2 1 6 2, 
2 0 0 8.( A bstr act) 
  
 8.   Je m al A, Sie gel R, W ar d E, M urr a y T, X u J, T h u n M J.  C a ncer st atistics, 2 0 0 7.  C A C a ncer J 
Cli n 5 7: 4 3- 6 6, 2 0 0 7. 
  
 9.   Ries, L. A. G., H ar ki ns, D., Kr a pc h o, M., M ari ott o, A., Miller, B. A., Fe uer, E. J., Cle g g, L., 
Eis ner, M. P., H or ner, M. J., H o wl a der, N., H a y at, M., H a n ke y, B. F., a n d E d w ar ds, B. K. 
(e ds). S E E R C a ncer St atistics Re vie w, 1 9 7 5- 2 0 0 3.  Bet hes d a, M D:  N ati o n al C a ncer 
I nstit ute, htt p://seer.c a ncer. g o v/csr/ 1 9 7 5 _ 2 0 0 3/ , b ase d o n N o ve m ber 2 0 0 5 S E E R d at a 
 
s u b missi o n, p oste d t o t he S E E R w e b site, 2 0 0 6. 
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Pr ot oc ol 2 3 6 8. 0 0 
3 5 
  
 1 0.   S mit h B D, S mit h G L, H urri a A, H ort o b a g yi G N, B uc h h olz T A.  F ut ure of c a ncer i nci de nce i n 
t he U nite d St ates: b ur de ns u p o n a n a gi n g, c h a n gi n g n ati o n.  J Cli n O nc ol 2 7: 2 7 5 8- 2 7 6 5, 
2 0 0 9. 
  
 1 1.   T all m a n M S, Gillil a n d D G, R o w e J M.  D r u g t her a p y f or ac ute m y el oi d le u ke mi a.  Bl o o d 1 0 6: 
1 1 5 4- 1 1 6 3, 2 0 0 5. 
  
 1 2.   T all m a n M S.  Ne w str ate gies f or t he tre at me nt of ac ute m y el oi d le u ke mi a i ncl u di n g a nti b o dies 
a n d ot her n o vel a ge nts. I n: Berli ner N, Lee S J, Li ne n ber ger M, V o gels a n g G B  (e ds):  
He m at ol o g y 2 0 0 5: A meric a n S ociet y of He mt ol o g y E d uc ati o n Pr o gr a m B o o k.  
W as hi n gt o n, D C:  A meric a n S ociet y of He m at ol o g y, p. 1 4 3- 1 5 0, 2 0 0 5. 
  
 1 3.   We d di n g U, R o hri g B, Kli p pstei n A, Pie nt k a L, H off ke n K.  A ge, se vere c o m or bi dit y a n d 
f u ncti o n al i m pair me nt i n de pe n de ntl y c o ntri b ute t o p o or s ur vi v al i n c a ncer p atie nts.  J 
C a ncer R es Cli n O nc ol 1 3 3: 9 4 5- 9 5 0, 2 0 0 7. 
  
 1 4.   v a n S pr o nse n D J, J a nsse n-Heij ne n M L, Bree d W P, C o e ber g h J W.  Pre v ale nce of c o -m o r bi dit y 
a n d its rel ati o ns hi p t o tre at me nt a m o n g u nselecte d p atie nts wit h H o d g ki n's dise ase a n d 
n o n- H o d g ki n's l y m p h o m a, 1 9 9 3 - 1 9 9 6.  A n n He m at ol 7 8: 3 1 5- 3 1 9, 1 9 9 9. 
  
 1 5.   Grei mel E R, P a dill a G V, Gr a nt M M.  P h ysic al a n d ps yc h os oci al o utc o mes i n c a ncer p atie nts: a 
c o m p aris o n of diff ere nt a ge gr o u ps.  Br J C a ncer 7 6: 2 5 1- 2 5 5, 1 9 9 7. 
  
 1 6.   K urtz M E, K urtz J C, St o m mel M, Gi ve n C W, Gi ve n B.  T he i nfl ue nce of s y m pt o ms, a ge, 
c o m or bi dit y a n d c a ncer site o n p h ysic al f u ncti o ni n g a n d me nt al he alt h of geri atric 
w o me n p atie nts.  W o me n & He alt h 2 9: 1- 1 2, 1 9 9 9. 
  
 1 7.   Gi ve n  C W, Gi ve n B, Azz o uz F, St o m mel M, K o z ac hi k S.  C o m p aris o n of c h a n ges i n p h ysic al 
f u ncti o ni n g of el derl y p atie nts wit h ne w di a g n oses of c a ncer.  Me d C are 3 8: 4 8 2- 4 9 3, 
2 0 0 0. 
  
 1 8.   Pi nt o A, Z a g o nel V, Ferr ar a F.  Ac ute m y el oi d le u ke mi a i n t he el derl y: bi ol o g y a n d t her a pe utic 
str ate gies ( Re vie w).  C ritic al Re vie ws i n O nc ol o g y- He m at ol o g y 3 9: 2 7 5- 2 8 7, 2 0 0 1. 
  
 1 9.   v a n S pr o nse n D J, J a nsse n-Heij ne n M L, Le m me ns V E, Peters W G, C o e ber g h J W.  I n de pe n de nt 
pr o g n ostic eff ect of c o -m o r bi dit y i n l y m p h o m a p atie nts: res ults of t he p o p ul ati o n -b ase d 
Ei n d h o ve n C a ncer Re gistr y.  E ur J C a ncer 4 1: 1 0 5 1- 1 0 5 7, 2 0 0 5. 
  
 2 0.   E xter m a n n M, O verc as h J, L y m a n G H, P arr J, B al d ucci L.  C o m or bi dit y a n d f u ncti o n al st at us 
are i n de pe n de nt i n ol der c a ncer p atie nts.  J Cli n O nc ol 1 6: 1 5 8 2 - 1 5 8 7, 1 9 9 8. 
  
 2 1.   G ol d w asser P, Fel d m a n J.  Ass oci ati o n of ser u m al b u mi n a n d m ort alit y ris k ( Re vie w).  J Cli n 
E pi de mi ol 5 0: 6 9 3- 7 0 3, 1 9 9 7.  
 
  
 2 2.   D ur ke n M, Herr nri n g C, Fi nc k h B, N a gel S, Nielse n P, Fisc her R, Ber ger H M, M ois o n R M, 
Pic hl mei er U, K o hlsc h utter B, Z a n der A R, K o hlsc h utter A.  I m p aire d pl as m a 
a nti o xi d ati ve def e nse a n d i ncre ase d n o ntr a nsferri n -b o u n d ir o n d uri n g hi g h -d ose 
c he m ot her a p y a n d r a di oc he m ot her a p y prece di n g b o ne m arr o w tr a ns pl a nt ati o n.  Free 
R a dic Bi ol Me d 2 8: 8 8 7- 8 9 4, 2 0 0 0. 
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 2 3.   E v e ns A M, Me ht a J, G or d o n LI.  R ust a n d c orr osi o n i n he m at o p oietic ste m cell tr a ns pl a nt ati o n: 
t he pr o ble m of ir o n a n d o xi d ati ve stress.  B o ne M arr o w Tr a ns pl a nt 3 4: 5 6 1- 5 7 1, 2 0 0 4. 
  
 2 4.   K at a o k a K, N a n n y a Y, H a n g ais hi A, I m ai Y, C hi b a S, T a k a h as hi T, K ur o k a wa M.  I nfl ue nce of 
pretr a ns pl a nt ati o n ser u m f erriti n o n n o nrel a pse m ort alit y after m yel o a bl ati ve a n d 
n o n m yel o a bl ati ve all o ge neic he m at o p oietic ste m cell tr a ns pl a nt ati o n.  Bi ol Bl o o d M arr o w 
Tr a ns pl a nt 1 5: 1 9 5- 2 0 4, 2 0 0 9. 
  
 2 5.   K a n d a J, Miz u m ot o C, Ic hi n o he T, K a w a b at a H, S ait o T, Y a m as hit a K, K o n d o T, T a k a k ur a S, 
Ic hi y a m a S, Uc hi y a m a T, Is hi k a w a T.  Pretr a ns pl a nt ser u m ferriti n a n d C-re acti ve 
pr otei n as pre dicti ve f act ors f or e arl y b acteri al i nfecti o n after all o ge neic he m at o p oietic 
cell tr a ns pl a nt ati o n.  B o ne M arr o w Tr a ns pl a nt 4 6: 2 0 8- 2 1 6, 2 0 1 1. 
  
 2 6.   Ri d ker P M, Rif ai N, St a m pf er M J, H e n ne ke ns C H.  Pl as m a c o nce ntr ati o n of i nterle u ki n - 6 a n d 
t he ris k of f ut ure m y o c ar di al i nf arcti o n a m o n g a p p are ntl y he alt h y me n.  Circ ul ati o n 1 0 1: 
1 7 6 7- 1 7 7 2, 2 0 0 0. 
  
 2 7.   Be nr as hi d M, M o yers K, M o ht y M, S a v a ni B N.  Vit a mi n D deficie nc y, a ut oi m m u nit y, a n d gr aft-
vers us - h ost- dise ase ris k: i m plic ati o n f or pre ve nti ve t her a p y.  E x p He m at ol 4 0: 2 6 3- 2 6 7, 
2 0 1 2. 
  
 2 8.   Ri n g dé n O, H or o witz M M, G ale R P, Bi g gs J C, G aje ws ki J, Ri m m A A, S pec k B, Ve u m - St o n e J A, 
de Witte T, B orti n M M.  O utc o me after all o ge n eic b o ne m arr o w tr a ns pl a nt f or le u ke mi a 
i n ol der a d ults.  J A M A 2 7 0: 5 7- 6 0, 1 9 9 3. 
  
 2 9.   Dee g H J, A p pel b a u m F R.  He m at o p oietic ste m cell tr a ns pl a nt ati o n i n p atie nts wit h 
m y el o d ys pl astic s y n dr o me ( R e vie w).  Le u k Res 2 4: 6 5 3- 6 6 3, 2 0 0 0. 
  
 3 0.   de Witte T, S uci u S, Ver h oef G, L a b ar B, Arc hi m b a u d E, A ul C, Sellesl a g D, Ferr a nt A, 
Wijer m a ns P, M a n delli F, A m a d ori S, Je h n U, M u us P, B o o g aerts M, Zitt o u n R, 
Gr at w o hl A, Z wierzi n a H, H a ge meijer A, Wille mze R.  I nte nsi ve c he m ot her a p y f oll o w e d 
b y all o ge neic or a ut ol o g o us ste m cell tr a ns pl a nt ati o n f or p atie nts wit h m y el o d ys pl astic 
s y n dr o mes ( M D Ss) a n d ac ute m yel oi d le u ke mi a f oll o wi n g M D S.  Bl o o d 9 8: 2 3 2 6- 2 3 3 1, 
2 0 0 1. 
  
 3 1.   G u ar di ol a P, R u n de V, B aci g al u p o A, R u ut u T, L oc atelli F, B o o g aerts M A, P a gli uc a A, 
C or nelisse n J J, Sc h o ute n H C, C arrer as E, Fi n ke J, v a n Bieze n A, Br a n d R, Nie der wieser 
D, Gl uc k m a n E, de Witte T M, S u bc o m mittee f or M yel o d ys pl astic S y n dr o mes of t he 
C hr o nic Le u k ae mi a W or ki n g Gr o u p of t he E ur o pe a n Bl o o d a n d M arr o w 
Tr a ns pl a nt ati o n Gr o u p.  Retr os pecti ve c o m p aris o n of b o ne m arr o w a n d gr a n ul oc yte 
c ol o n y-sti m ul ati n g f act or- m o bilize d peri p her al bl o o d pr o ge nit or cells f or all o ge neic ste m 
cell tr a ns pl a nt ati o n usi n g H L A i de ntic al si bli n g d o n ors i n m yel o d ys pl astic s y n dr o mes.  
Bl o o d 9 9: 4 3 7 0- 4 3 7 8, 2 0 0 2. 
 
  
 3 2.   Sierr a J, Pérez W S, R o z m a n C, C arrer as E, Kl ei n J P, Rizz o J D, D a vies S M, L az ar us H M, 
Bre des o n C N, M ar ks DI, C a n als C, B o o g aerts M A, G ol d m a n J, C h a m pli n R E, Ke ati n g 
A, Weis d orf D J, de Witte T M, H or o witz M M.  B o ne m arr o w tr a ns pl a nt ati o n f r o m H L A-
i de ntic al si bli n gs as tre at me nt f or m yel o d ys pl asi a.  Bl o o d 1 0 0: 1 9 9 7- 2 0 0 4, 2 0 0 2. 
I R B A p pr o v e d 
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 3 3.   Mc S w ee ne y P A, Nie der wieser D, S hiz ur u J A, S a n d m aier B M, M oli n a A J, M al o ne y D G, 
C h a u nce y T R, G o ole y T A, He ge n b art U, N as h R A, R a dic h J, W a g ner J L, Mi n or S, 
A p pel b a u m F R, Be nsi n ger WI, Br y a nt E, Fl o w ers M E D, Ge o r ges G E, Gr u met F C, Kie m 
H- P, T or o k- St o r b B, Y u C, Bl u me K G, St o r b R F.  He m at o p oietic cell tr a ns pl a nt ati o n i n 
ol der p atie nts wit h he m at ol o gic m ali g n a ncies: re pl aci n g hi g h- d ose c yt ot o xic t her a p y wit h 
gr aft- vers us -t u m or eff ects.  Bl o o d 9 7: 3 3 9 0- 3 4 0 0, 2 0 0 1. 
  
 3 4.   de Li m a M, A n a g n ost o p o ul os A, M u nsell M, S h a hj a h a n M, Ue n o N, I p p oliti C, A n derss o n B S, 
G aje ws ki J, C o uriel D, C ortes J, D o n at o M, Ne u m a n n J, C h a m pli n R, Gir alt S.  
N o n a bl ati ve vers us re d uce d -i nte nsit y c o n diti o ni n g re gi me ns i n t he tre at me nt of ac ute 
m y el oi d le u ke mi a a n d hi g h -ris k m yel o d ys pl astic s y n dr o me: d ose is rel e v a nt f or l o n g-ter m 
dise ase c o ntr ol after all o ge neic he m at o p oietic ste m cell tr a ns pl a nt ati o n.  Bl o o d 1 0 4: 8 6 5-
8 7 2, 2 0 0 4. 
  
 3 5.   de Li m a M, C o uri el D, T h all P F, W a n g X, M a d de n T, J o nes R, S h p all E J, S h a hj a h a n M, Pierre 
B, Gir alt S, K o r bli n g M, R ussell J A, C h a m pli n R E, A n derss o n B S.  O nce- d ail y 
i ntr a ve n o us b uslf a n a n d fl u d ar a bi ne: cli nic al a n d p h ar m a c o ki netic res ults of a 
m y el o a blti ve, re d uce d -t o xicit y c o n diti o ni n g re gi me n f or all o ge neic ste m cell 
tr a ns pl a nt ati o n i n A M L a n d M D S.  Bl o o d 1 0 4: 8 5 7- 8 6 4, 2 0 0 4. 
  
 3 6.   Kr o g er N, B or n h a user M, E h ni n ger G, Sc h w er dtfe ger R, Biers ac k H, S a yer H G, W a n dt H, 
Sc h af er - Ec k ar dt K, Be yer J, Kie hl M, Z a n der A R.  All o ge neic ste m cell tr a ns pl a nt ati o n 
after a fl u d ar a bi ne/ b us ulf a n -b ase d re d uce d -i nte nsit y c o n diti o ni n g i n p atie nts wit h 
m y el o d ys pl astic s y n dr o me or sec o n d ar y ac ute m y el oi d le u ke mi a.  A n n He m at ol 8 2: 3 3 6-
3 4 2, 2 0 0 3. 
  
 3 7.   M arti n o R, C a b aller o M D, Si m ó n J A, C a n als C, S ol a n o C, Ur b a n o-Is píz u a A, B ar g a y J, Lé o n A, 
S arr á J, S a nz G F, M o r ale d a J M, Br u net S, S a n Mi g uel J, Sierr a J, A M L a n d all o P B S C T 
S u bc o m mitt ees of t he S p a nis h Gr o u p f or He m at o p oietic Tr a ns pl a nt ati o n.   E vi de nce f or a 
gr aft- vers us -le u ke mi a eff ect after all o ge neic peri p her al bl o o d ste m cell tr a ns pl a nt ati o n 
wit h re d uce d -i nte nsit y c o n diti o ni n g i n ac ute m yel o ge n o us le u ke mi a a n d m yel o d ys pl astic 
s y n dr o mes.  Bl o o d 1 0 0: 2 2 4 3- 2 2 4 5, 2 0 0 2. 
  
 3 8.   H o A Y L, P a gli uc a A, Ke n y o n M, P a r ker J E, Mij o vic A, De v ere u x S, M ufti G J.  Re d uce d -
i nte nsit y all o ge neic he m at o p oietic ste m cell tr a ns pl a nt ati o n f or m yel o d ys pl astic s y n dr o me 
a n d ac ute m y el oi d le u ke mi a wit h m ultili ne a ge d ys pl asi a usi n g fl u d ar a bi ne, b us ul p h a n 
a n d ale mt uz u m a b ( F B C) c o n diti o ni n g.  Bl o o d 1 0 4: 1 6 1 6- 1 6 2 3, 2 0 0 4. 
  
 3 9.   C h a kr a vert y R, Pe g gs K, C h o pr a R, Milli g a n D W, K ott ari dis P D, Verf uert h S, Ge ar y J, 
T h ur ais u n d ar a m D, Br a ns o n K, C h a kr a b arti S, M a he n dr a P, C r a d d oc k C, P ar ker A, 
H u nter A, H ale G, W al d m a n n H, Willi a ms C D, Y o n g K, Li nc h D C, G ol dst o ne A H, 
M ac ki n n o n S.  Li miti n g tr a ns pl a nt ati o n -rel ate d m o rt alit y f oll o wi n g u nrel ate d d o n or ste m 
cell tr a ns pl a nti o n b y usi n g a n o n m yel o a bl ati ve c o n diti o ni n g re gi me n.  Bl o o d 9 9: 1 0 7 1-
1 0 7 8, 2 0 0 2. 
 
  
 4 0.   He ge n b art U, Nie der wieser D, S a n d m ai er B M, M aris M B, S hiz ur u J A, Grei ni x H, C or d o n nier 
C, Ri o B, Gr at w o hl A, L a n ge T, Al- Ali H, St orer B, M al o ne y D, Mc S w ee ne y P, C h a u nce y 
T, A g ur a E, Br u n o B, M azi arz R T, Peterse n F, St or b R.  Tre at me nt f or ac ute 
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m y el o ge n o us le u ke mi a b y l o w- d ose, t ot al- b o d y, irr a di ati o n-b ase d c o n diti o ni n g a n d 
he m at o p oietic cell tr a ns pl a nt ati o n fr o m rel ate d a n d u nrel ate d d o n ors.  J Cli n O nc ol 2 4: 
4 4 4- 4 5 3, 2 0 0 6. 
  
 4 1.   G y ur k ocz a B, St or b R F, St orer B, C h a u nce y T, Nie der wieser D, S hiz ur u J, L a n gst o n A, 
P ulsi p her M, Bre des o n C, M azi arz R T, Br u n o B, Peters e n F, M aris M, A g ur a E, Ye a ger 
A M, Bet h ge W A, S a he bi F, Vi n del o v L, Mc S w ee ne y P A, A p pel b a u m F R, M al o ne y D G, 
S a n d m aier B M.  N o n m yel o a bl ati ve all o ge neic he m at o p oietic cell tr a ns pl a nt ati o n i n 
p atie nts wit h de n o v o a n d sec o n d ar y ac ute m y el oi d le u ke mi a. Bl o o d  1 1 2: 6 1, # 1 4 9, 
2 0 0 8.( A bstr act) 
  
 4 2.   S a n d m aier B M, St or b R.  Re d uce d -i nte nsit y c o n diti o ni n g f oll o w e d b y he m at o p oietic cell 
tr a ns pl a nt ati o n f or he m at ol o gic m ali g n a ncies. I n: A p pel b a u m F R, F or m a n S J, Ne g ri n 
R S, Bl u me K G (e ds):  T h o m as' He m at o p oietic Cell Tr a ns pl a nt ati o n.  O xf or d, U K:  
Wile y - Bl ac k w ell, p. 1 0 4 3- 1 0 5 8, 2 0 0 9. 
  
 4 3.   Li m Z, Br a n d R, M arti n o R, v a n Bieze n A, Fi n ke J, B aci g al u p o A, Beele n D, De ver gi e A, 
Aless a n dri n o E, Wille mze R, R u ut u T, B o o g aerts M, F al d a M , J o uet J P, Nie der wieser D, 
Kr o g er N, M ufti G J, de Witte T M.  All o ge neic he m at o p oietic ste m -cell tr a ns pl a nt ati o n 
f or p atie nts 5 0 ye ars or ol der wit h m yel o d ys pl astic s y n dr o mes or sec o n d ar y ac ute 
m y el oi d le u ke mi a.  J Cli n O nc ol 2 8: 4 0 5- 4 1 1, 2 0 1 0. 
  
 4 4.   Mc C l u ne B L, Weis d orf D J, Pe derse n T L, T u nes d a Sil v a G, T all m a n M S, Sierr a J, Di Persi o J, 
Ke ati n g A, G ale R P, Ge or ge B, G u pt a V, H a h n T, Is ol a L, J a g asi a M, L az ar us H, M ar ks 
D, M azi arz R, W aller E K, Bre des o n C, Gir alt S.  Effect of a ge o n o utc o me of re d uce d -
inte nsit y he m at o p oieti c cell tr a ns pl a nt ati o n f or ol der p atie nts wit h ac ute m yel oi d 
le u ke mi a i n first c o m plete re missi o n or wit h m yel o d ys pl astic s y n dr o me.  J Cli n O nc ol 2 8: 
1 8 7 8- 1 8 8 7, 2 0 1 0. 
  
 4 5.   S orr or M L, S a n d m aier B M, St orer B E, Fr a n ke G N, L a p ort G G, C h a u nce y T R, A g ur a E, 
M azi arz R T, L a n gst o n A, H ari P, P ulsi p her M A, Bet h ge W, S a he bi F, Br u n o B, M aris 
M B, Ye a ger A, Peters e n F B, Vi n del ø v L, Mc S w ee ne y P A, H ü bel K, Mielc are k M, 
Ge o r ges G E, Nie der wieser D, Bl u me K G, M al o ne y D G, St or b R.  L o n g -ter m o utc o mes 
a m o n g ol der p atie nts f oll o wi n g n o n m yel o a bl ati ve c o n diti o ni n g a n d all o ge neic 
he m at o p oietic cell tr a ns pl a nt ati o n f or a d v a nce d he m at ol o gic m ali g n a ncies.  J A M A 3 0 6: 
1 8 7 4- 1 8 8 3, 2 0 1 1.  P M CI D: P M C 3 2 1 7 7 8 7 
  
 4 6.   P as q ui ni M C, W a n g Z.  C urre nt use a n d o utc o me of he m at o p oietic ste m cell tr a ns pl a nt ati o n: 
CI B M T R S u m m ar y Sli des, 2 0 1 0.  A v ail a ble at: htt p:// w w w  ci b mtr o r g 2 0 1 0. 
  
 4 7.   Este y E, de Li m a M, Ti bes R, Pierce S, K a nt arji a n H, C h a m pli n R, Gir alt S.  Pr os pecti ve 
f e asi bilit y a n al ysis of re d uce d -i nte nsit y c o n diti o ni n g ( RI C) re gi me ns f or he m at o p oietic 
ste m cell tr a ns pl a nt ati o n ( H S C T) i n el derl y p atie nts wit h ac ute m yel oi d le u ke mi a ( A M L) 
a n d hi g h -ris k m yel o d ys pl astic s y n dr o me ( M D S).  Bl o o d 1 0 9: 1 3 9 5- 1 4 0 0, 2 0 0 7. 
 
  
 4 8.   A p pel b a u m F R.  W h at  is t he i m p act of he m at o p oietic cell tr a ns pl a nt ati o n ( H C T) f or ol der a d ults 
wit h ac ute m yel oi d le u ke mi a ( A M L) ?  B est Pr a ctice & Rese a rc h Cli nic al H ae m at ol o g y 
2 1: 6 6 7- 6 7 5, 2 0 0 8.  P M CI D: P M C 3 1 6 3 8 4 9 
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 4 9.   A n derss o n I, A hl ber g K, St oc kel ber g D, Br u ne M, Pers s o n L-O.  He alt h -rel ate d q u alit y of life i n 
p atie nts u n der g oi n g all o ge neic ste m cell tr a ns pl a nt ati o n after re d uce d i nte nsit y 
c o n diti ni n g vers us m yel o a bl ati ve c o n diti o ni n g.  C a ncer N urs 3 2: 3 2 5- 3 3 4, 2 0 0 9. 
  
 5 0.   M ol assi otis A, v a n de n A k ker O B, Milli g a n D W, G ol d m a n J M, B o u g ht o n B J, H ol mes J A, 
T h o m as S.  Q u alit y of lif e i n l o n g-ter m s ur vi v ors of m arr o w tr a ns pl a nt ati o n: c o m p aris o n 
wit h a m atc he d gr o u p recei vi n g m ai nte n a nce c he m ot her a p y.  B o ne M arr o w Tr a ns pl a nt 
1 7: 2 4 9- 2 5 8, 1 9 9 6. 
  
 5 1.   W ats o n M, W he atle y K, H arris o n G A, Zitt o u n R, Gr a y R G, G ol dst o ne A H, B ur nett A K.  Se v ere 
a d verse i m p act o n se x u al f u ncti o ni n g a n d fertilit y of b o ne m arr o w tr a ns pl a nt ati o n, eit her 
all o ge neic or a ut ol o g o us, c o m p are d wit h c o ns oli d ati o n c he m ot her a p y al o ne: a n al ysis of 
t he M R C A M L 10 tri al.  C a ncer 8 6: 1 2 3 1- 1 2 3 9, 1 9 9 9. 
  
 5 2.   Se keres M A, St o ne R M, Z a hrie h D, Ne u ber g D, M orris o n V, De A n gel o D J, G ali ns k y I, Lee S J.  
Decisi o n - m a ki n g a n d q u alit y of life i n ol der a d ults wit h ac ute m yel oi d le u ke mi a or 
a d v a nce d m yel o d ys pl astic s y n dr o me.  Le u ke mi a 1 8: 8 0 9- 8 1 6, 2 0 0 4. 
  
 5 3.   De g ner L F, Sl o a n J A.  Decisi o n m a ki n g d uri n g seri o us ill ness: w h at r ole d o p atie nts re all y w a nt 
t o pl a y ?  J Cli n E pi de mi ol 4 5: 9 4 1- 9 5 0, 1 9 9 2. 
  
 5 4.   Bl a nc h ar d C G, L a brec q ue M S, R uc k desc hel J C, Bl a nc h ar d E B.  I nf or m ati o n  a n d decisi o n -
m a ki n g pref ere nces of h os pit alize d a d ult c a ncer p atie nts.  S oci al Scie nce & Me dici ne 2 7: 
1 1 3 9- 1 1 4 5, 1 9 8 8. 
  
 5 5.   C assilet h B R, Z u p kis R V, S utt o n -S mit h K, M a rc h V.  I nf or m ati o n a n d p artici p ati o n prefere nces 
a m o n g c a ncer p atie nts.  A n n I nter n Me d 9 2: 8 3 2- 8 3 6, 1 9 8 0. 
  
 5 6.   L a Vel a S L, S mit h B, We a ver F M, Mis ke vics S A.  Ge o g r a p hic al pr o xi mit y a n d he alt h c are 
utiliz ati o n i n veter a ns wit h S CI & D i n t he U S A.  S oci al Scie nce & Me dici ne 5 9: 2 3 8 7 - 2 3 9 9, 
2 0 0 4. 
  
 5 7.   P a g a n o E, Di C u o nz o D, B o n a C, B al di I, G a briele P, Ric ar di U, R ott a P, Bertett o O, A p pi a n o S, 
Merletti F, Se g n a n N, Cicc o ne G.  Accessi bilit y as a m aj or deter mi n a nt of r a di ot her a p y 
u n der utiliz ati o n: a p o p ul ati o n b ase d st u d y.  He alt h P olic y 8 0: 4 8 3- 4 9 1, 2 0 0 7. 
  
 5 8.   Dej ar di n O, B o u vier A M, Her bert C, V elte n M, B ue mi A, Del af osse P, M a a r o uf N, B o utre u x S, 
L a u n o y G.  S oci al a n d ge o gr a p hic dis p arities i n access t o refere nce c a re site f or p atie nts 
wit h c ol orect al c a ncer i n Fr a nce.  Br J C a ncer 9 2: 1 8 4 2- 1 8 4 5, 2 0 0 5. 
  
 5 9.   R a o K, D a rri n gt o n D L, Sc h u m ac her J J, De vette n M, V ose J M, L o beri z a F R, Jr.  Dis p arit y i n 
s ur vi v al o utc o me after he m at o p oietic ste m cell tr a ns pl a nt ati o n f or he m at ol o gic 
m ali g n a ncies acc o r di n g t o are a of pri m ar y resi de nce.  Bi ol Bl o o d M arr o w Tr a ns pl a nt 1 3: 
1 5 0 8- 1 5 1 4, 2 0 0 7. 
 
  
 6 0.   A b o u - N ass ar K E, Ki m H T, Bl oss o m J, H o V T, S oiffer R J, C utler C S, Al ye a E P, K oret h J, A nti n 
J H, Ar m a n d P.  T he i m p act of ge o gr a p hic pr o xi mit y t o tr a ns pl a nt ce nter o n o utc o mes 
after all o ge neic he m at o p oietic ste m cell tr a ns pl a nt ati o n.  Bi ol Bl o o d M arr o w Tr a ns pl a nt 
1 8: 7 0 8- 7 1 5, 2 0 1 2. 
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 6 1.   Rizz o J D, Wi n g ar d J R, Tic helli A, Lee S J, v a n Li nt M T, B ur ns L J, D a vies S M, Ferr a r a J L M, 
S ocié G.  R ec o m me n de d scree ni n g a n d pre ve nti ve pr actices f or l o n g -ter m s ur vi v ors after 
he m at o p oietic cell tr a ns pl a nt ati o n: j oi nt rec o m me n d ati o ns of t he E ur o pe a n Gr o u p f or 
Bl o o d a n d M arr o w Tr a ns pl a nt ati o n, t he Ce nter f or I nter n ati o n al Bl o o d a n d M arr o w 
Tr a ns pl a nt Rese arc h, a n d t he A meric a n S ociet y of Bl o o d a n d M arr o w Tr a ns pl a nt ati o n.  
Bi ol Bl o o d M arr o w Tr a ns pl a nt 1 2: 1 3 8- 1 5 1, 2 0 0 6. 
  
 6 2.   B a ker K S, D a vies S M, M aj h ail N S, H asse br oe k A, Klei n J P, B alle n K K, Bi gel o w C L, Fr a n g o ul 
H A, H ar d y C L, Bre des o n C, De h n J, Frie d m a n D, H a h n T, H ale G, L az ar us H M, 
Le M aistre C F, L o beriz a F, M a h a r aj D, Mc C art h y P, Setter h ol m M, S pell m a n S, Tri g g 
M, M azi arz R T, S witzer G, Lee S J, Rizz o J D.  R ace a n d s oci oec o n o mi c st at us i nfl ue nce 
o utc o mes of u nrel ate d d o n or he m at o p oieti c cell tr a ns pl a nt ati o n.  Bi ol Bl o o d M arr o w 
Tr a ns pl a nt 1 5: 1 5 4 3- 1 5 5 4, 2 0 0 9.  P M CI D: P M C 2 7 7 5 8 1 9 
  
 6 3.   E xter m a n n M, A a pr o M, Ber n a bei R, C o he n H J, Dr oz J P, Lic ht m a n S, M or V, M o nf ar di ni S, 
Re pett o L, S or b ye L, T o pi n k o v a E, T as k F orce o n C G A of t he I nter n ati o n al S ociet y of 
Geri atric O nc ol o g y.  Us e of c o m pre he nsi ve geri atric assess me nt i n ol der c a ncer p atie nts: 
rec o m me n d ati o ns f r o m t he t as k f orce o n C G A of t he I nter n ati o n al S ociet y of Geri atric 
O nc ol o g y ( SI O G) ( Re vi e w).  Critic al Re vie ws i n O nc ol o g y- He m at ol o g y 5 5: 2 4 1- 2 5 2, 2 0 0 5. 
  
 6 4.   H urri a A, Cirri nci o ne C T, M uss H B, K or n blit h A B, B arr y W, Artz A S, Sc h mie der L, A ns ari R, 
Te w W P, Wec kstei n D, Kir s h ner J, T o g a w a K, H a nse n K, K at heri a V, St o ne R, G ali ns k y 
I, P osti gli o ne J, C o he n H J.  I m ple me nti n g a geri atric assess me nt i n c o o per ati ve gr o u p 
cli nic al c a ncer tri als: C A L G B 3 6 0 4 0 1.  J Cli n O nc ol 2 9: 1 2 9 0- 1 2 9 6, 2 0 1 1. 
  
 6 5.   H urri a A, T o g a w a K, M o hile S G, O w us u C, Kle pi n H D, Gr oss C P, Lic ht m a n S M, G ajr a A, 
B h ati a S, K at heri a V, Kl a p per S, H a nse n K, R a m a ni R, L ac hs M, W o n g F L, Te w W P.  
Pre dicti n g c he m ot her a p y t o xicit y i n ol der a d ults wit h c a ncer: a pr os pecti ve m ultice nter 
st u d y.  J Cli n O nc ol 2 9: 3 4 5 7- 3 4 6 5, 2 0 1 1. 
  
 6 6.   Kle pi n H D, Gei ger A M, T o oze J A, Kritc he vs k y S B, Willi a ms o n J D, P a r dee T S, Ellis L R, P o w ell 
B L.  Geri atri c assess me nt pre dicts s ur vi v al f or ol der a d ults recei vi n g i n d ucti o n 
c he m ot her a p y f or ac ute m y el o ge n o us le u ke mi a.  Bl o o d 1 2 1: 4 2 8 7- 4 2 9 4, 2 0 1 3. 
  
 6 7.   Fri e d L P, T a n ge n C M, W alst o n J, Ne w m a n A B, Hirsc h C, G ott die ner J, See m a n T, Tr ac y R, 
K o p W J, B ur ke G, Mc B ur nie M A, C ar di o v asc ul ar He alt h St u d y C oll a b or ati ve Rese a rc h 
Gr o u p.  Fr ailt y i n ol der a d ults: e vi de nce f or a p he n ot y pe.  J o ur n als of Ger o nt ol o g y Series 
A- Bi ol o gic al Scie nces & Me dic al Scie nces 5 6: M 1 4 6 - M 1 5 6, 2 0 0 1. 
  
 6 8.   S her m a n A E, M ot yc k o v a G, Fe g a K R, De A n gel o D J, A bel G A, Stee ns m a D, W a dlei g h M, St o ne 
R M, Dri ver J A.  Geri at ric assess me nt i n ol der p atie nts wit h ac ute m yel oi d le u ke mi a : a 
retr os pecti ve st u d y of ass oci ate d tre at me nt a n d o utc o mes.  Le u k Res 3 7: 9 9 8 - 1 0 0 3, 2 0 1 3. 
 
  
 6 9.   Desc hler B, I h orst G, Pl atz bec ker U, Ger mi n g U, M arz E, de Fi g ueri d o M, Fritzs c he K, H a as P, 
S ali h H R, Gi a g o u ni dis A, Sellesl a g D, L a b ar B, de Witte T, Wije r m a ns P, L u b bert M.  
P ar a met ers det ecte d b y geri atric a n d q u alit y of life assess me nt i n 1 9 5 ol der p atie nts wit h 
m y el o d ys pl astic s y n dr o mes a n d ac ute m yel oi d le u ke mi a a re hi g hl y pre dicti ve f or 
o utc o me.  H ae m at ol o gic a 9 8: 2 0 8- 2 1 6, 2 0 1 3. 
I R B A p pr o v e d 
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Pri nte d o n 4/ 2 2/ 2 0 1 9
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 7 0.   St u de ns ki S, P erer a S, P at el K, R os a n o C, F a ul k ner K, I nzit ari M, Br ac h J, C h a n dler J, 
C a wt h o n P, C o n n or E B, Ne vitt M, Visser M, Kritc he vs k y S, B a di nelli S, H arris T, 
Ne w m a n A B, C a ule y J, Ferr ucci L, G ur al ni k J.  G ait s pee d a n d s ur vi v al i n ol der a d ults.  
J A M A 3 0 5: 5 0- 5 8, 2 0 1 1. 
  
 7 1.   G ur al ni k J M, Ferr ucci L, Pie per C F, Le veille S G, M a r ki des K S, Ostir G V, St u de ns ki S, 
Ber k m a n L F, W all ace R B.  L o w er e xtre mit y f u ncti o n a n d s u bse q ue nt dis a bilit y: 
c o nsiste nc y acr oss st u dies, pre dicti ve m o dels, a n d v al ue of g ait s pee d al o ne c o m p a re d 
wit h t he s h ort p h ysic al perf or m a nce b atter y.  J o ur n als of Ger o nt ol o g y Series A-
Bi ol o gic al Scie nces & Me dic al Scie nces 5 5: M 2 2 1 - M 2 3 1, 2 0 0 0. 
  
 7 2.   M uffl y L S, B o ul u k os M, S w a ns o n K, K oc her gi ns k y M, Cerr o P D, Sc h r oe der L, P a pe L, 
E xter m a n n M, v a n Besie n K, Artz A S.  Pil ot st u d y of c o m pre he nsi ve geri atric ass ess me nt 
( C G A) i n all o ge neic tr a ns pl a nt: C G A c a pt ures a hi g h pre v ale nce of v ul ner a bilities i n 
ol der tr a ns pl a nt reci pie nts.  Bi ol Bl o o d M arr o w Tr a ns pl a nt 1 9: 4 2 9- 4 3 4, 2 0 1 3. 
  
 7 3.   S orr or M L, M a ri s M B, St orer B, S a n d m aier B M, Di ac o nesc u R, Fl o w ers C, M al o ne y D G, St o r b 
R.  C o m p ari n g m o r bi dit y a n d m ort alit y of H L A- m atc he d u nrel ate d d o n or he m at o p oietic 
cell tr a ns pl a nt ati o n after n o n m yel o a bl ati ve a n d m y el o a bl ati ve c o n diti o ni n g: i nfl ue nce of 
pretr a ns pl a nt c o m or bi dities.  Bl o o d 1 0 4: 9 6 1- 9 6 8, 2 0 0 4. 
  
 7 4.   S orr or M L, M a ris M B, St or b R, B ar o n F, S a n d m aier B M, M al o ne y D G, St orer B.  
He m at o p oietic cell tr a ns pl a nt ati o n ( H C T) -s pecific c o m or bi dit y i n de x: a ne w t o ol f or ris k 
assess me nt bef ore all o ge neic H C T.  Bl o o d 1 0 6: 2 9 1 2- 2 9 1 9, 2 0 0 5. 
  
 7 5.   H arrell F E, Jr., Lee K L, M ar k D B.  M ulti v ari a ble pr o g n ostic m o dels: iss ues i n de vel o pi n g 
m o dels, e v al u ati n g ass u m pti o ns a n d a de q u ac y, a n d me as uri n g a n d re d uci n g err ors 
( Re vie w).  St at Me d 1 5: 3 6 1- 3 8 7, 1 9 9 6. 
  
 7 6.   J o nes R B.  H C T o utc o mes: a ne w t o ol ?  Bl o o d 1 0 6: 2 6 0 2- 2 6 0 3, 2 0 0 5. 
  
 7 7.   Re gi d or E, G u all ar-C astill o n P, G utierrez - Fis a c J L, B a ne g as J R, R o dri g uez- Art al ej o F.  
S oci oec o n o mic v ari ati o n i n t he m a g nit u de of t he ass oci ati o n bet w ee n self -r ate d he alt h 
a n d m ort alit y.  A n n E pi de mi ol 2 0: 3 9 5- 4 0 0, 2 0 1 0. 
  
 7 8.   C hes o n B D, Be n nett J M, K o pec k y K J, B uc h ner T, Will m a n C L, Este y E H, Sc hiffer C A, 
D oe h ner H, T all m a n M S, Lister T A, L o- C oc o F, Wille mze R, Bi o n di A, Hi d de m a n n W, 
L ars o n R A, L o w e n ber g B, S a nz M A, He a d D R, O h n o R, Bl o o mfiel d C D, I nter n ati o n al 
W or ki n g Gr o u p f or Di a g n osis S o R C T O a R Sf T Ti A M L.  Re vise d rec o m me n d ati o ns of t he 
I nter n ati o n al W or ki n g Gr o u p f or Di a g n osis, St a n d ar diz ati o n of Res p o nse Criteri a, 
Tre at me nt O ut c o mes, a n d Re p orti n g St a n d ar ds f or T her a pe utic Tri als i n Ac ute M yel oi d 
Le u ke mi a [ err at u m a p pe ars i n J Cli n O nc ol. 2 0 0 4 Fe b 1; 2 2( 3): 5 7 6].  J Cli n O nc ol 2 1: 
4 6 4 2- 4 6 4 9, 2 0 0 3. 
 
  
 7 9.   C hes o n B D, Gree n ber g P L, Be n nett J M, L o w e n ber g B, Wijer m a ns P, Ni mer S D, Pi nt o A, Ber a n 
M, de Witte T M, St o ne R M, Mittel m a n M, S a nz G F, G ore S D, Sc hiffer C A, K a nt a rji a n 
H.  Cli nic al a p plic ati o ns a n d pr o p os al f or m o dific ati o n of t he I nter n ati o n al W or ki n g 
Gr o u p (I W G) res p o nse criteri a i n m y el o d ys pl asi a.  Bl o o d 1 0 8: 4 1 9- 4 2 5, 2 0 0 6. 
I R B A p pr o v e d 
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Pri nte d o n 4/ 2 2/ 2 0 1 9
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 8 0.   D u H, D a vi ds o n P M, E verett B, S al a m o ns o n Y, Zecc hi n R, R olle y J X, Ne wt o n P J, M a c d o n al d 
P S.  C orrel ati o n bet w ee n a self -a d mi nistere d w al k test a n d a st a n d ar dise d Si x Mi n ute 
W al k Test i n a d ults.  N ursi n g & He alt h Scie nces 1 3: 1 1 4- 1 1 7, 2 0 1 1. 
  
 8 1.   D u H, D a vi ds o n P M, E verett B, S al a m o ns o n Y, Zecc hi n R, R olle y J X, Ne wt o n P J, M a c d o n al d 
P S.  Assess me nt of a self -a d mi nistere d a d a pte d 6 - mi n ute w al k test.  J o ur n al of 
C ar di o p ul m o n ar y Re h a bilit ati o n & Pre v e nti o n 3 0: 1 1 6- 1 2 0, 2 0 1 0. 
  
 8 2.   Mc Q uell o n R P, R ussell G B, Cell a D F, C r a ve n B L, Br a d y M, B o n o mi A, H ur d D D.  Q u ality of 
lif e me as ure me nt i n b o ne m a rr o w tr a ns pl a nt ati o n: de vel o p me nt of t he F u ncti o n al 
Assess me nt of C a ncer T her a p y -B o ne M arr o w Tr a ns pl a nt ( F A C T -B M T) sc ale.  B o ne 
M arr o w Tr a ns pl a nt 1 9: 3 5 7- 3 6 8, 1 9 9 7. 
  
 8 3.   A n dr y k o ws ki M A.  Ps y c h os oci al f act ors i n b o ne m arr o w tr a ns pl a nt ati o n: a re vie w a n d 
rec o m me n d ati o ns f or rese arc h ( Re vie w).  B o ne M arr o w Tr a ns pl a nt 1 3: 3 5 7 - 3 7 5, 1 9 9 4. 
  
 8 4.   A ge nc y f or He alt hc are Rese arc h a n d Q u alit y.  U. S. v al u ati o n of t he E ur o Q ol E Q- 5 D he alt h 
st ates.  htt p:// w w w  a hr q g o v/rice/ E Q 5 D pr oj ht m 2 0 0 5. 
  
 8 5.   S yrj al a K L, St o ver A C, Yi J C, Art her h olt S B, A br a ms J R.  Me as uri n g s oci al acti vities a n d 
s oci al f u ncti o n i n l o n g-ter m c a ncer s ur vi v ors w h o recei ve d he m at o p oietic ste m cell 
tr a ns pl a nt ati o n.  Ps yc h o- O nc ol o g y 1 9: 4 6 2- 4 7 1, 2 0 1 0.  P M CI D: P M C 3 1 1 4 5 5 5 
  
 8 6.   L o gs d o n R G, Teri L.  T he Ple as a nt E ve nts Sc h e d ule-A D: ps yc h o metri c pr o perties a n d 
rel ati o ns hi p t o de pressi o n a n d c o g niti o n i n Alz hei mer's dise ase p atie nts.  Ger o nt ol o gist 
3 7: 4 0- 4 5, 1 9 9 7. 
  
 8 7.   E N RI C H D I n vesti g at ors.   E n h a nci n g rec o ver y i n c or o n ar y he art dise ase ( E N RI C H D): b aseli ne 
c h ar acteristics.  A m J C ar di ol 8 8: 3 1 6- 3 2 2, 2 0 0 1. 
  
 8 8.   E N RI C H D I n vesti g at ors.  E n h a nci n g rec o ver y i n c or o n ar y he art dise ase p atie nts ( E N RI C H D): 
st u d y desi g n a n d met h o ds.  A m He a rt J 1 3 9: 1- 9, 2 0 0 0. 
  
 8 9.   M assie M J.  Pre v ale nce of de pressi o n i n p atie nts wit h c a ncer ( Re vie w).  J o ur n al of t he N ati o n al 
C a ncer I nstit ute M o n o gr a p hs 3 2: 5 7- 7 1, 2 0 0 4. 
  
 9 0.   B a d ger T A, Br a de n C J, Mis hel M H.  De pressi o n b ur de n, self -hel p i nter ve nti o ns, a n d si de effect 
e x perie nce i n w o me n recei vi n g tre at me nt f or bre ast c a ncer.  O N F 2 8: 5 6 7 - 5 7 4, 2 0 0 1. 
  
 9 1.   K u n y S, St asse n H H.  C o g niti ve perf or m a nce i n p atie nts rec o v eri n g fr o m de pressi o n.  
Ps yc h o p at h ol o g y 2 8: 1 9 0- 2 0 7, 1 9 9 5. 
  
 9 2.   B a d ger T A, Br a de n C J, Mis hel M H , L o n g m a n A.  De pressi o n b ur de n, ps yc h ol o gic al a dj ust me nt, 
a n d q u alit y of lif e i n w o me n wit h bre ast c a ncer: p atter ns o ver ti me.  R ese arc h i n N ursi n g 
& He alt h 2 7: 1 9- 2 8, 2 0 0 4. 
 
  
 9 3.   St o m mel M, Gi ve n B A, Gi ve n C W.  De pressi o n a n d f u ncti o n al st at us as pre di ct ors of de at h 
a m o n g c a ncer p atie nts.  C a ncer 9 4: 2 7 1 9- 2 7 2 7, 2 0 0 2.  
I R B A p pr o v e d 
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Pri nte d o n 4/ 2 2/ 2 0 1 9
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 9 4.   L o beriz a F R J, Rizz o J D, Bre des o n C N, A nti n J H, H or o witz M M, Wee ks J C, Lee S J.  
Ass oci ati o n of de pressi ve s y n dr o me a n d e arl y de at hs a m o n g p atie nts after ste m- cell 
tr a ns pl a nt ati o n f or m ali g n a nt dise ases.  J Cli n O nc ol 2 0: 2 1 1 8- 2 1 2 6, 2 0 0 2. 
  
 9 5.   S pitzer R L, Kr oe n ke K, Willi a ms J B.  V ali d ati o n a n d utilit y of a self-re p ort versi o n of P RI M E -
M D: t he P H Q pri m ar y c are st u d y. Pri m a r y C a re E v al u ati o n of Me nt al Dis or ders. P atie nt 
He alt h Q uesti o n n aire.  J A M A 2 8 2: 1 7 3 7- 1 7 4 4, 1 9 9 9.  
  
 9 6.   Kr o e n ke K, S pitzer R L, Willi a ms J B.  T he P H Q - 9: v ali dit y of a brief de pressi o n se verit y 
me as ure.  J o ur n al of Ge ner al I nter n al Me dici n e 1 6: 6 0 6 - 6 1 3, 2 0 0 1. 
  
 9 7.   L o w e B, Kr oe n ke K, Herz o g W, Gr afe K.  Me as uri n g de pressi o n o utc o me wit h a brief self -
re p ort i nstr u me nt: se nsiti vit y t o c h a n ge of t he P ati e nt He alt h Q uesti o n n aire ( P H Q - 9).  
J o ur n al of Aff ecti ve Dis or ders 8 1: 6 1- 6 6, 2 0 0 4. 
  
 9 8.   L o w e B, U n utzer J, C all a h a n C M, Per ki ns A J, Kr o e n ke K.  M o nit ori n g de pressi o n tre at me nt 
o utc o mes wit h t he p atie nt he alt h q uesti o n n aire - 9.  Me d C are 4 2: 1 1 9 4- 1 2 0 1, 2 0 0 4. 
  
 9 9.   Ste w art A L, K a m ber g C J.  P h ysic al f u ncti o ni n g me as ures. I n: Ste w art A L, W are J E (e ds):  
Me as uri n g f u ncti o ni n g a n d w ell -bei n g; t he Me dic al O utc o mes St u d y a p pr o ac h.  D ur h a m, 
N C:  D u ke U ni versit y Press, p. 8 6 - 1 0 1, 1 9 9 2. 
   1 0 0.   M ulti di me nsi o n al f u ncti o n al assess me nt of ol der a d ults: t he D u ke Ol der A meric a ns Res o urces 
a n d Ser vices pr oce d ures.  Hills d ale, N J:  L a w re nce Erl b a u m Ass o ci ates, I nc., 1 - 1 4 5, 2 0 0 5. 
   1 0 1.   H ol mes - R o v ner M, Kr oll J, Sc h mitt N, R o v ner D R, Breer M L, R ot hert M L, P a d o n u G, 
T al arcz y k G.  P ati e nt s atisf acti o n wit h he alt h c are decisi o ns: t he s atisf acti o n wit h 
decisi o n sc ale.  Me d Decis M a ki n g 1 6: 5 8 - 6 4, 1 9 9 6. 
   1 0 2.   C astell M V, S á nc hez M, J uli á n R, Q uei p o R, M artí n S, Oter o A.  Fr ailt y pre v ale nce a n d sl o w 
w al ki n g s pee d i n pers o ns a ge 6 5 a n d ol der: i m plic ati o ns f or pri m ar y c are.  B M C F a mil y 
Pr a ctice 1 4: 8 6, 2 0 1 3. 
   1 0 3.   P o dsi a dl o D, Ric h ar ds o n S.  T he ti me d " U p & G o ": a test of b asic f u ncti on al m o bilit y f or fr ail 
el derl y pers o ns.  J o ur n al of t he A meric a n Geri atrics S ociet y 3 9: 1 4 2 - 1 4 8, 1 9 9 1. 
   1 0 4.   K a w as C, K ar a gi o zis H, Res a u L, C orr a d a M, Br o o k me y er R.  Reli a bilit y of t he Blesse d 
Tele p h o ne I nf or m ati o n -Me m o r y - C o nce ntr ati o n Test.  J o ur n al of Geri atric Ps yc hi atr y & 
Ne ur ol o g y 8: 2 3 8- 2 4 2, 1 9 9 5. 
   1 0 5.   K atz m a n R, Br o w n T, F ul d P, Pec k A, Sc hec hter R, Sc hi m mel H.  V ali d ati o n of a s h ort 
Orie nt ati o n -Me m o r y - C o nce ntr ati o n Test of c o g niti ve i m p air me nt.  A meric a n J o ur n al of 
Ps yc hi at r y 1 4 0: 7 3 4- 7 3 9, 1 9 8 3. 
 
   1 0 6.   Wil diers H, Heere n P, P uts M, T o pi n k o v a E, J a nsse n- Heij ne n M L, E xter m a n n M, F al a n dr y C, 
Artz A, Br ai n E, C oll oc a G, Fl a m ai n g J, K a r n a kis T, Ke nis C, A u disi o R A, M o hile S, 
Re pett o L, v a n Lee u w e n B, Milise n K, H urri a A.  I nter n ati o n al S ocieit y of Geri atri c 
O nc ol o g y c o nse ns us o n geri atric ass ess me nt i n ol der p atie nts wit h c a ncer ( R e vie w).  J 
Cli n O nc ol 3 2: 2 5 9 5- 2 6 0 3, 2 0 1 4. 
I R B A p pr o v e d 
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Pri nte d o n 4/ 2 2/ 2 0 1 9
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Pr ot oc ol 2 3 6 8. 0 0 
4 4 
   1 0 7.   B ar o n F, M a ris M B, S a n d m aier B M, St o rer B E, S orr or M, Di ac o nes c u R, W o olfre y A E, 
C h a u nce y T R, Fl o w ers M E D, Mielc are k  M, M al o ne y D G, St or b R.  Gr aft-vers us -t u m or 
eff ects after all o ge neic he m at o p oietic cell tr a ns pl a nt ati o n wit h n o n m yel o a bl ati ve 
c o n diti o ni n g.  J Cli n O nc ol 2 3: 1 9 9 3- 2 0 0 3, 2 0 0 5. 
   1 0 8.   Wei L J, Li n D Y, Weissfel d L.  Re gressi o n a n al ysis of m ulti v ari ate i nc o m plete f ail ure ti me d at a 
b y m o deli n g m a r gi n al distri b uti o ns.  J A m St at Ass oc 8 4: 1 0 6 5- 1 0 7 3, 1 9 8 9. 
   1 0 9.   P D Q St atisti cs.  T or o nt o:  B. C. Dec ker, 1 7 2 p p, 1 9 8 6. 
   1 1 0.   Ei nsie del H G, v o n S A, H art m a n n R, Fe n gler R, Sc hr a p pe M, J a n k a-Sc h a u b G, M a n n G, H a hle n 
K, G o bel U, Kli n ge biel T, L u d wi g W D, He nze G.  L o n g- ter m o utc o me i n c hil dre n wit h 
rel a pse d A L L b y ris k -str atifie d s al v a ge t her a p y: res ults of tri al ac ute l y m p h o bl astic 
le u ke mi a-rel a pse st u d y of t he Berli n -Fr a n kf urt -M u nster Gr o u p 8 7.[ Err at u m a p pe ars i n 
J Cli n O nc ol. 2 0 0 8 M a y 1; 2 6( 1 3): 2 2 3 8].  J Cli n O nc ol 2 3: 7 9 4 2- 7 9 5 0, 2 0 0 5. 
   1 1 1.   Fi ne J P, Gr a y R J.  A pr o p orti o n al h az ar ds m o del f or t he s u b distri b uti o n of a c o m peti n g ris k.  J 
A m St at Ass oc 9 4: 4 9 6- 5 0 9, 1 9 9 9. 
   1 1 2.   R ose n b a u m P R, R u bi n D B.  T he ce nt r al r ole of t he pr o pe nsit y sc ore i n o bser v ati o n al st u dies f or 
c a us al eff ects.  Bi o met ri k a 7 0: 4 1- 5 5, 1 9 8 3. 
   1 1 3.   C urtis L H, H a m mill B G, Eise nstei n E L, Kr a mer J M, A nstr o m K J.  Usi n g i n verse pr o b a bilit y -
w ei g hte d esti m at o rs i n c o m p ar ati ve effecti ve ness a n a l yses wit h o bser v ati o n al d at a b ases.  
Me d C are 4 5: S 1 0 3 - S 1 0 7, 2 0 0 7. 
   1 1 4.   R ose n b a u m P R.  M o del- b ase d direct a dj ust me nt.  J A m St at Ass oc 8 2: 3 8 7- 3 9 4, 1 9 8 7. 
   1 1 5.   C ole S R, Her n a n M A.  A dj uste d s ur vi v al c ur ves wit h i n verse pr o b a bilit y w ei g hts.  C o m p uter 
Met h o ds & Pr o gr a ms i n Bi o me dici ne 7 5: 4 5 - 4 9, 2 0 0 4. 
   1 1 6.   Hir a n o K, I m be ns G W.  Esti m ati o n of c a us al effects usi n g pr o pe nsit y sc ore w ei g hti n g: a n 
a p plic ati o n t o d at a o n ri g ht he art c at heteriz ati o n.  He alt h Ser vices a n d O utc o mes 
Rese arc h Met h o d ol o g y 2: 2 5 9- 2 7 8, 2 0 0 1. 
   1 1 7.   Li n D Y, Ps at y B M, Kr o n m al R A.  Ass essi n g t he se nsiti vit y of re gressi o n res ults t o u n me as ure d 
c o nf o u n ders i n o bser v ati o n al st u dies.  Bi o metri cs 5 4: 9 4 8- 9 6 3, 1 9 9 8. 
   1 1 8.   Ze ger S L, Li a n g K Y.  M o dels f or l o n git u di n al d at a: a ge ner alized esti m ati n g e q u ati o n a p pr o ac h 
[ p u blis he d err at u m a p pe ars i n Bi o metrics 1 9 8 9 M ar; 4 5( 1): 3 4 7].  Bi o metrics 4 4: 1 0 4 9-
1 0 6 0, 1 9 8 8. 
 
   1 1 9.   M o u nier N, H ai o u n C, C ole B F, Gissel brec ht C, Se b b a n C, M orel P, M arit G, B o u a b d all a h R, 
R a v oet C, S alles G, Re y es F, Le p a g e E.  Q u alit y of life- a dj uste d s ur vi v al a n al ysis of hi g h-
d ose t her a p y wit h a ut ol o g o us b o ne m arr o w tr a ns pl a nt ati o n vers us se q ue nti al 
c he m ot her a p y f or p atie nts wit h a g gressi ve l y m p h o m a i n first c o m plete re missi o n. Gr o u pe 
d' Et u de les L y m p h o mes de l' A d ulte ( G E L A).  Bl o o d 9 5: 3 6 8 7- 3 6 9 2, 2 0 0 0. 
I R B A p pr o v e d 
D o c u m e nt R el e a s e D at e: 0 6/ 1 8/ 2 0 1 8
Pri nte d o n 4/ 2 2/ 2 0 1 9
Printed on 4/22/2019

Pr ot oc ol 2 3 6 8. 0 0 
4 5 
1 2 0. P ars o ns S K, Gel ber S, C ole B F, R a vi n dr a n at h Y, O g de n A, Ye a ger A M, C h a n g M, S h uster J,
Wei nstei n H J, Gel ber R D.  Q u alit y -a dj uste d s ur vi v al after tre at me nt f or ac ute m y el oi d 
le u ke mi a i n c hil d h o o d: A Q- T Wi S T a n al ysis of t he Pe di atric O nc ol o g y Gr o u p St u d y 
8 8 2 1.  J Cli n O nc ol 1 7: 2 1 4 4- 2 1 5 2, 1 9 9 9. 
1 2 1.  Gl aszi o u P P, Si mes R J, Gel ber R D.  Q u alit y a dj uste d s ur vi v al a n al ysis ( Re vie w).  St at Me d 9:
1 2 5 9- 1 2 7 6, 1 9 9 0. 
1 2 2.
Gel ber R D, G ol d hirsc h A.  A ne w e n d p oi nt f or t he assess me nt of a dj u v a nt t her a p y i n
p ost me n o p a us al w o me n wit h o per a ble bre ast c a ncer.  J Cli n O nc ol 4: 1 7 7 2- 1 7 7 9, 1 9 8 6. 
I R B A p pr o v e d 
D o c u m e nt R el e a s e D at e: 0 6/ 1 8/ 2 0 1 8
Pri nte d o n 4/ 2 2/ 2 0 1 9
Printed on 4/22/2019