ORIGINAL ARTICLE
Current results on the use of imatinib mesylate in patients withrelapsed philadelphia chromosome positive leukemia after
allogeneic or syngeneic hematopoietic stem celltransplantation
Andrew J. Ullmann, Georg Hess, Karin Kolbe, A. Friedrich-Freksa1, Ralf G. Meyer, Harald Gschaidmeier2
Christoph Huber and Thomas Fischer
3rd Medical Department, Johannes Gutenberg-University, 1Institute for Clinical Genetics, Mainz
2Novartis Pharma, Nürnberg, Germany(Received for publication on March 10, 2003)

Abstract. Here, we describe a patient diagnosed with chronic myelogenous leukemia who relapsed
after matched unrelated donor SCT. The patient was treated with imatinib mesylate and donor lymphocyte infusions, and achieved a complete molecular remission. Additionally, safety and efﬁcacy of
imatinib mesylate in a total of 134 patients from 8 centers who underwent allogeneic or syngeneic stem
cell transplantation (SCT) and had a relapse of Philadelphia chromosome positive leukemia wasreviewed. Data was compiled from abstracts accepted as oral or poster presentations at the ASH(American Society of Hematology) 2001 and EBMT (European Group for Blood and Marrow Transplantation) 2001 & 2002 meetings and additionally literature published on this patient group. Efﬁcacy
of imatinib therapy was assessed by morphology, cytogenetic analysis, and determination of donor
chimerism. In the evaluable population, hematologic and cytogenetic responses were observed in 66%
and 60% of the patients, respectively. Fifty-one of 114 (45%) patients achieved a complete cytogenetic
response. No response or progress of disease was noted in 22 out of evaluable 91 patients. The observation period was limited to a maximum of 28 months. A signiﬁcant improvement in donor chimerism
was frequently observed. Only ﬁve cases of signiﬁcant GVHD were reported. Preliminary results showthat imatinib mesylate has the potential to positively inﬂuence the ratio of donor and recipient cells
without inducing a high incidence of severe GVHD. The data suggest that earlier start of imatinib
mesylate prior to hematologic relapse in minimum residual disease (MRD) positive patients is apromising treatment concept. (Keio J Med 52 (3): 182–188, September 2003)
Key words: STI-571, imatinib mesylate, allogeneic, syngeneic, transplantation

Introduction
Allogeneic stem cell transplantation is the therapyof choice for a selected patient population with chronic
myelogenous leukemia (CML).1 Overall, long term disease free survival after transplantation is accomplishedin up to 70% of eligible patients.2
In patients transplanted in chronic phase of CML,
relapse after allogeneic stem cell transplantation (SCT)

is noted in 5 to 30% of the cases. The incidence rateof relapse in patients transplanted in more advanced
stages of disease is signiﬁcantly higher. Currently,interferon-a, donor lymphocyte infusions (DLIs) or asecond allogeneic SCT are alternatives to treat relapse
after allogeneic transplantation. DLIs from the original
SC donor result in complete molecular remissions in ahigh proportion of relapsed CML patients and are currently considered standard of care. However, patients

Presented at the 1256th Meeting of the Keio Medical Society in Tokyo, May 31, 2002.
Reprint requests to: Dr. Andrew J. Ullmann, Klinikum der Johannes Gutenberg-Universität, III. Medizinische Klinik & Poliklinik, Langenbeckstr. 1, 55101 Mainz, Germany, facimile þ49 6131 17 476564, e-mail: A.Ullmann@3-med.klinik.uni-mainz.de182

Keio J Med 2003; 52 (3): 182–188

in accelerated phase or blast crisis respond poorly to
DLIs with response rates between 0 and 30%.3–5 In theevent of donor unavailability, other curable therapeutic
approaches do not exist.
The disadvantage of DLIs is the potential development of graft-versus-host-disease (GVHD) which is amajor contributing factor of morbidity and mortality
in this patient population. Up to 60% of the patients
receiving DLIs experience GVHD.5,6 If donor hematopoiesis is missing, DLIs induce bone marrow aplasia
which can be long lasting and is also associated withan increased morbidity and mortality rate. Application of DLIs is contraindicated in patients with preexisting GVHD. DLIs administered in an escalated
dose scheme reduce the incidence of GVHD without
reducing its efﬁcacy.7,8Imatinib presents an interesting alternative in thetreatment of relapsed CML after allogeneic SCT. Imatinib mesylate is a selective inhibitor of the abl proteintyrosine kinase.9–11 Philadelphia (Ph) chromosomepositive leukemia presents an ideal target for therapy
with imatinib mesylate because the bcr-abl kinase plays
a dominant role in deregulated cell proliferation. It has
recently been approved by the FDA (Food and Drug
Administration) and EMEA (The European Agency
for the Evaluation of Medical Products) for patientsin chronic phase of CML intolerant or refractory tointerferon-a, and for patients in accelerated phaseor blast crisis. In clinical trials imatinib mesylate
induced a high rate of hematologic and cytogenetic
responses in bcr-abl positive CML with a low toxicity
proﬁle.12–14
Materials and Methods
Patients
Here we report on a patient who received imatinib
mesylate for relapsed CML following matched unrelated donor stem cell transplantation. Additionally, we
compiled data from abstracts accepted as oral or poster
presentations at the ASH (American Society for Hematology) 2001 and EBMT 2001 & 2002 meetings. Thisfar, only two papers were published on patients withrelapsed Philadelphia chromosome positive leukemia
after allogeneic transplantation.15,16 Abstracts were
only selected if more than 5 patients were reported tohave relapsed after allogeneic or syngeneic transplantation and received imatinib.15–26 If numerous submissions from the same group were available, only thelatest submission was considered. Abstracts were notconsidered if their content did not differentiate between
autologous and allogeneic transplantation.
A total of 134 patients from 8 centers underwent allogeneic or syngeneic stem cell transplantation and had

183

a relapse of the Philadelphia chromosome positive leukemia (Table 1).
One-hundred patients were in blast crisis, relapseof Philadelphia chromosome positive ALL, in an accelerated phase (including additional chromosomal
abnormalities), or had extramedullar manifestation(high-risk group). The remaining 34 patients were in
the chronic phase/cytogenetic relapse group. The timeinterval since transplantation ranged between 1–234
months.
In abstracts where data was available, twenty-threepatients received HLA-identical donor transplantation,
10 patients received matched unrelated donor transplantation, 3 patients received mismatched donor transplantation and additional 4 patients were transplantedwith a syngeneic donor transplant. The only available
information on the remaining patients was that an allogeneic transplantation had been performed. Treatment
with imatinib mesylate was initiated at a single daily
oral dose of 400 mg for the chronic phase/cytogenetic
relapse group or 600–1000 mg for high-risk group.
Treatment duration ranged between 1–28 months.
Efﬁcacy was assessed by peripheral blood and bonemarrow evaluations, cytogenetic analysis, and determination of donor chimerism.
Molecular analysis
PCR-positivity for bcr-abl and breakpoint characteristics of the CML patient in our case report were evaluated by utilizing a nested PCR procedure as publishedpreviously.27 For follow-up evaluation, a commerciallyavailable quantitative PCR (qPCR) assay was applied
using hybridization probes and detection on the LightCycler device (Roche, Mannheim, Germany). This assay can quantify levels above 1 : 10 4 translocation bearing cells. In brief, mononuclear cells (MNC) of bloodor bone marrow samples were prepared and RNA wasextracted using a commercially available kit (HighPure
RNA extraction kit, Roche, Mannheim, Germany) or astandard protocol using tripure reagent (Roche, Mannheim, Germany). cDNA synthesis was performed according to the manufacturers’ instruction and real-time
PCR was performed using a deﬁned amount of thetranscription product. Using a second PCR-reaction asinternal standard resulted in expression of bcr-abl levels
relative to GAPDH-levels. To avoid interassay variation, samples of each patient were analyzed in a single
run whenever possible. If qPCR did not result in aquantiﬁable result, nested PCR was performed to evaluate for remaining minimal residual disease with a maximum sensitivity of 1 : 10 5 –10 6 .
Chimerism analyses were performed in bone marrowand peripheral mononuclear cells by analysis of shorttandem repeat systems.

184

Ullmann AJ, et al: Current results on the use of imatinib mesylate in patients

Table 1 Summary of Abstracts Approved for Oral or Poster Presentation at EBMT and ASH Meetings 2001 and 2002. The Results of the Two
Publications are Also Included
AuthorPatients
Median time
SCT-STI
Treatment
duration(median)
Hematologic
response
Cytogenetic
response
Complete
cytogenetic
response
Molecular
remission
GVHD >2
or chronic
extensive
GVHD
Other toxicity

Kantarjian
et al.15,19

ChambonPautas
et al.18

Wassmann/
Pfeifer
et al.21,25

Soiffer
et al.22

Rodrieguez
et al.16

Ottmann/
Wassmann
et al.20,26

Ullmann
et al.23,24

28
1–137 months

15
9–132 months

11 months19

2–15 months

21
6.5 months(2–50)
4.6 months

18/2419

10/10

17/28

Au
et al.17

16
12 months(2–24)
N/A

8
N/A

20
N/A

8
N/A

4 months

N/A

18
17 months(2–234)6 months

13/21

9/11

7/8

11/20

12/18

N/A

8/10

6/17

4/5

N/A

N/A

N/A

6/8

11/28

5/10

7/13

4/9

4/8

11/20

3/18

6/8

1/28

1/10

4/6

N/A

Unknown

1

2

1

3

0

[3/21
GVHD nograding]

N/A

0 (3 active
GVHD atstart)

1 gut

0

1

6/14 >II NCI
granulocytopenia
4/15 >II NCI
thrombocytopenia

4 cytopenia

3 subdural
hygroma/hematoma 1
neutropenic
colitis 12/21>II
cytopenia

4 LFT
increase(3
GVHD, 1leukemia),
2 BM
hypoplasia

2 rash &cytopenia

1
aspergillosis& MOF

6/18 >II
NCI
cytopenia,
musclecramps2/8
cytopenia,
musclecramps

N/A

N/A: not available; NCI: NCI/NIH Common Toxicity Criteria.

Case report
A previously healthy 32-year-old woman was diagnosed in November 1994 with Philadelphia chromosome positive CML. Treatment with hydroxyurea andinterferon-a was started and no siblings were available
as donors for a transplant. HLA-matched unrelateddonor stem cell transplantation was performed in Julyof 1998. The post transplantation phase was complicated by a grade III GVHD of the skin. She received
cyclosporine A (CSP) and prednisolone for immunosuppressive therapy. Steroids were tapered within 2months and then discontinued. Post transplantation, amolecular remission documented by nested PCR wasnoted. CSP was being tapered when consecutive blood
samples turned positive for bcr-abl (ﬁrst noted 268 days
after transplantation). Despite slow tapering of CSP
due to ongoing limited chronic GVHD, 402 days after
transplantation negativity for bcr-abl was not accomplished. Chronic limited GVHD was constantly eminent
during tapering and after discontinuation of the immunosuppressive therapy. DLI was not feasible due todonor unavailability at that time.

After 570 days post transplantation, the patient developed accelerated phase (AP) of CML. Imatinib
mesylate treatment was initiated with 400 mg once
daily. Therapy was well tolerated by the patient except for mild muscle cramps. Prior to imatinib mesylate treatment, cytogenetic analysis revealed 100%
Philadelphia chromosome positive (Phþ) recipient
metaphases. After three months, cytogenetic analysis
demonstrated three divergent types of metaphases:
Philadelphia chromosome negative recipient (XX),Philadelphia chromosome positive recipient (XX,t),9,22
and donor cells (XY). After a total of 180 days of imatinib treatment, no Philadelphia chromosome positive
metaphases were detectable (Fig. 1). The percentage ofdonor metaphases increased to 80% after additional
180 days, the proportion of Ph-negative recipient metaphases was at 20%. Again, no Philadelphia chromosome positive cells were detectable during the patient’s
further clinical course.
After one year, chimerism analysis revealed a change
from undetectable donor chimerism at initiation of imatinib to 68% in the bone marrow and to 73% in the
peripheral blood. This increase in donor chimerism

Keio J Med 2003; 52 (3): 182–188

185

Fig. 1 Cytogenetic analysis, PCR and chimerism assessment during treatment with imatinib in a 34 year-old woman with CML, who relapsed
after MUD transplantation. Chimerism was analyzed in bone marrow (BM) mononuclear cells. The level of detection for donor chimerism is at
5% donor cells. At initiation of imatinib therapy there was no detectable donor chimerism. [*: not done]. Not all metaphases were considered in
the counts, since various structural and numeral chromosome aberrations were additionally observed and were considered neither pathogenic
nor a cell line.

was detectable within 6 months of imatinib therapy anddid not change signiﬁcantly thereafter. Simultaneously,levels of bcr-abl mRNA transcripts, as evaluated byquantitative PCR, decreased rapidly (Fig. 1) without
reaching complete molecular remission by nested PCR.
Thus, in this patient who had relapsed in AP of CML atstart of imatinib mesylate therapy, minimum residual
disease (MRD) was achieved.
Consequently, in June 2001, the patient received aﬁrst dose of DLI (1  10 6 CD3 positive cells/kg) and in
October 2001 a second dose (5  10 6 CD3 positive cells/kg). Of note, imatinib mesylate therapy was continued
and no signiﬁcant side-effects were noted. After thesecond DLI, leukocytes dropped brieﬂy to 2000/ml andthe dosage of imatinib mesylate was decreased inter-mittently to 300 mg qd. Thereafter, a sustained complete molecular remission, evaluated by nested PCR,
was accomplished without developing severe GVHD.
Only limited chronic GVHD of the skin was clinicallyobserved. The above noted mixed chimerism (donor
cells and Ph-negative recipient cells) remained unchanged. The patient continues on imatinib mesylate.
Results of the Literature Review
Table 1 depicts essential data on efﬁcacy and toxicity
of imatinib mesylate therapy derived from abstracts
reviewed. Overall, 80 of 112 evaluable patients (71%)(Table 1) showed some hematologic response and 66
of 99 evaluable patients achieved a complete hemato-

186

Ullmann AJ, et al: Current results on the use of imatinib mesylate in patientslogic response. No response or progress of disease wasreported in 22 out of 91 evaluable patients. Most ofthese patients were in the high risk group (beyond
chronic phase).
Overall cytogenetic responses were observed in 41 of
68 evaluable patients (60%) (Table 1). In 51 patientsout of 114 evaluable patients (45%) a complete cytogenetic response was noted (Table 1). Where discrimination between low and high risk patients was possible,
it was reported that 6 of evaluable 13 patients (46%)
in the low risk group (chronic phase at the initiationof imatinib mesylate) and 25 of evaluable 48 patients(52%) in the high-risk group developed a complete
cytogenetic response.
Mixed chimerism was noted in numerous patients attherapy initiation. Limited available data demonstrated
that donor chimerism increased after the start of imatinib in responding patients. Most abstracts and literature
were not equipped with detailed data concerning donor
chimerism.
Generally, imatinib mesylate was well tolerated. Relevant treatment related side effects were reported tobe limited with mild to moderate gastrointestinal discomfort, elevated liver function tests (of which GVHD
could be a cause) and muscle cramps. In 34 of 134(25%) evaluable patients, greater than grade II (NCI/
NIH common toxicity criteria) myelosuppression (anemia, thrombocytopenia and/or neutropenia) was observed. This was reported to be mostly reversible andresponded to dose reduction.
Symptoms of chronic extensive or >II acute GVHD
were reported in ﬁve patients. In another three patients
who experienced a grade III acute GVHD at start ofimatinib mesylate no exacerbation was observed.
Twenty patients died due to refractory or progressive disease. Most of these patients were members of
the high risk group.
Discussion
Imatinib is a selective tyrosine kinase inhibitor targeting bcr-abl, c-kit and PDGF-R kinases. Phase I and
II clinical trials using this drug demonstrated a high rateof hematologic and cytogenetic remissions in bcr-abl
positive leukemia without previous transplantation.29
The case report presented here and the preliminary
analysis of single center experiences derived fromabstracts presented at ASH 2001, EBMT 2001 & 2002,
and papers published to date show encouraging resultsfor patients with relapse of bcr-abl positive leukemia
after allogeneic or syngeneic transplantation.15–26
Imatinib was well tolerated in most patients. Nonhematological adverse events grade a II (as deﬁned by
NCI Common Toxicity Criteria) were frequently reported. Twenty-seven percent of the patients suffered>II myelosuppression, necessitating a dose reduction
and/or interruption of imatinib. Severe hematologicaladverse events occurred more frequently in the highrisk group suggesting that myelosuppression is primarily related to inadequate recovery of bcr-abl negative
hematopoiesis. Induction of GVHD is expected in patients, in which donor chimerism was increasing. However, in most of the patients reported here, GVHD was
not observed. Clinically signiﬁcant GVHD (more thangrade II of acute GVHD or chronic extensive GVHD)
was described in only ﬁve patients. At the start of imatinib mesylate, three patients had grade III GVHD, but
no exacerbation was reported.
Evaluable high risk patients experienced a hematologic response in approximately 61% of the cases anda cytogenetic response was noted in 52%. In the lowrisk population, hematologic and cytogenetic responses
were noted in 100% and 46% of the evaluable patients,
respectively. Complete cytogenetic responses were observed in 41% of all evaluable patients. The observation period was limited to a maximum of 28 months. In
comparison, Druker and colleagues reported in theirstudy a rate of 31% complete cytogenetic response inpatients with CML in chronic phase.29
Complete cytogenetic response is an important predictor for survival in interferon therapy.30 Its value
for imatinib mesylate is so far incompletely understood. However, preliminary data, derived from phase
II trials, predict a positive outcome in patients achieving a signiﬁcant cytogenetic response.
However, 14 of 22 patients, despite achieving a major or complete hematologic or cytogenetic response,
relapsed. All of these patients were in the high-risk
group. This advocates for additional therapy using
DLIs shortly after achievement of a maximal cytogenetic response to imatinib mesylate.
Real-time quantitative and qualitative (nested) PCR
demonstrated a complete molecular remission in thepatient depicted in Fig. 1, after introduction of DLI.
Other groups also reported complete molecular responses (Table 1). However, different molecular evaluation procedures and interlaboratory variations make acomparison of results difﬁcult. Two different systems
are utilized frequently, namely Taqman and LightCycler technology.28,31 Both systems allow quantiﬁcation of minimal residual disease within a sensitivity of
1 : 10 4 . In addition, comparison of results from various
laboratories is difﬁcult, as sample and RNA preparation
also inﬂuence the results.32
A signiﬁcant improvement in donor chimerism was
frequently observed without introducing or exacerbating GVHD (only reported in ﬁve patients). The patient
depicted in Fig. 1 showed the appearance of normal
bcr-abl negative recipient metaphases upon treatment
with imatinib mesylate. This demonstrates survival of

Keio J Med 2003; 52 (3): 182–188

recipient hematopoietic system cells despite myeloablative conditions (Fig. 1). No exacerbation of GVHD
or aplasia was observed. Surprisingly, upon DLI therapy the proportion of the Ph-negative recipient cells
was not signiﬁcantly altered despite a documented
achievement of PCR negativity for bcr-abl. Thus, the Tcell response derived from the donor apparently tolerates the Ph-negative recipient hematopoietic cells. This
argues for a speciﬁc leukemia-associated antigen recognized speciﬁcally by donor immunity.
In summary, imatinib mesylate demonstrates a novel
approach in treating relapsed Philadelphia positive leukemia after allogeneic SCT. Imatinib mesylate was generally well tolerated. The data presented here state thatthe most common side effects are mild and can easily be
managed. However, frequent monitoring, especially for
myelosuppression and hepatotoxicity, is required. Imatinib mesylate has the potential to positively inﬂuence
the ratio of donor and recipient cells without inducing
severe GVHD. The data presented suggests that earlier
start of imatinib mesylate prior to hematologic relapse
in a minimum residual disease situation is a promisingtreatment concept. Currently, a phase II clinical trial isin progress to prospectively evaluate this approach interms of toxicity and efﬁcacy.
References
1. Goldman JM, Druker BJ: Chronic myeloid leukemia: current
treatment options. Blood 2001; 98: 2039–2042
2. Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E,
Devergie A, Frassoni F, Gahrton G, Kolb HJ, Niederwieser D,
et al: Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic
Leukemia Working Party of the European Group for Blood andMarrow Transplantation. Lancet 1998; 352: 1087–1092
3. Dazzi F, Szydlo RM, Goldman JM: Donor lymphocyte infusions
for relapse of chronic myeloid leukemia after allogeneic stem
cell transplant: where we now stand. Exp Hematol 1999; 27:
1477–1486
4. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, Ljungman P, Ferrant A, Verdonck L, Niederwieser D, et al: Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Groupfor Blood and Marrow Transplantation Working Party Chronic
Leukemia. Blood 1995; 86: 2041–2050
5. Roman J, Alvarez MA, Torres A: Molecular basis for therapeutic decisions in chronic myeloid leukemia patients after allogeneic bone marrow transplantation. Haematologica 2000; 85:
1072–1082
6. Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S,
Champlin R, Goodman SA, Wolff SN, Hu W, Verfaillie C, et al:
Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin
Oncol 1997; 15: 433–444
7. Dazzi F, Szydlo RM, Craddock C, Cross NC, Kaeda J, Chase A,
Olavarria E, van Rhee F, Kanfer E, Apperley JF, et al: Comparison of single-dose and escalating-dose regimens of donor
lymphocyte infusion for relapse after allografting for chronic
myeloid leukemia. Blood 2000; 95: 67–71

187
8. Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins
NH, Boulad F, Castro-Malaspina H, Childs BH, Gillio AP, Kernan NA, et al: Adoptive immunotherapy evaluating escalating
doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graftversus-leukemia responses from graft-versus-host disease. Blood
86: 1261–1268
9. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB: Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive
cells. Nat Med 1996; 2: 561–566
10. Gambacorti-Passerini C, le Coutre P, Mologni L, Fanelli M,
Bertazzoli C, Marchesi E, Di Nicola M, Biondi A, Corneo GM,
Belotti D, et al: Inhibition of the ABL kinase activity blocks theproliferation of BCR/ABLþ leukemic cells and induces apoptosis. Blood Cells Mol Dis 1997; 23: 380–394
11. le Coutre P, Mologni L, Cleris L, Marchesi E, Buchdunger E,
Giardini R, Formelli F, Gambacorti-Passerini C: In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL
kinase inhibitor. J Natl Cancer Inst 1999; 91: 163–168
12. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C,
Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville
R, Zoellner U, et al: Hematologic and cytogenetic responses toimatinib mesylate in chronic myelogenous leukemia. N Engl J
Med 2002; 346: 645–652
13. Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB,
Ottmann OG, Schiffer CA, Talpaz M, Guilhot F, Deininger MW,
et al: Imatinib induces hematologic and cytogenetic responses inpatients with chronic myelogenous leukemia in myeloid blastcrisis: results of a phase II study. Blood 2002; 99: 3530–3539
14. Talpaz M, Silver RT, Druker BJ, Goldman JM, GambacortiPasserini C, Guilhot F, Schiffer CA, Fischer T, Deininger MW,
Lennard AL, et al: Imatinib induces durable hematologic andcytogenetic responses in patients with accelerated phase chronic
myeloid leukemia: results of a phase 2 study. Blood 2002; 99:
1928–1937
15. Kantarjian HM, O’Brien S, Cortes JE, Giralt SA, Rios MB, Shan
J, Giles FJ, Thomas DA, Faderl S, De Lima M, et al: Imatinib
mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2002; 100:
1590–1595
16. Rodriguez R, Snyder D, Nademanee A, O’Donnell M, Krishnan
A, Bhatia R, Slovak M, Resta D, Forman S: Gleevec for relapsed
CML after allogeneic transplant may overcome need for donor
leukocyte infusions (DLI) or interferon (IFN). Blood 2001; 98:
abstract 1684
17. Au WY, Lie AK, Ma SK, Wan TS, Liang R, Chan EC, Kwong
YL: Tyrosine kinase inhibitor STI571 in the treatment of Philadelphia chromosome-positive leukaemia failing myeloablative
stem cell transplantation. Bone Marrow Transplant 2002; 30:
453–457
18. Chambon-Pautas, Cony-Makhoul P, Giraudier S, Vigier M,
Michallet M, Guilhot F, Jouet JP, Berthaud P, Kuentz M: Glivec(STI571) Treatment for chronic myelogenous leukemia (CML)in relapse after allogeneic stem cell transplantation (SCT): a
report of the French experience (on behalf of the SFGM andFILMC). Blood 2001; 98: abstract 587
19. Kantarjian HM, O’Brien S, Cortes J, Giralt S, Beth Rios M,
Shan J, Giles F, Thomas D, Faderl S, de Lima M, et al: Results ofimatinib mesylate (STI571) therapy in patients (pts) with chronic
myelogenous leukemia (CML) in relapse after allogeneic stem
cell transplantation (allo SCT). Blood 2001; 98: Abstract 575
20. Ottmann OG, Wassmann B, Pfeifer H, Scheuring U, Thiede C,
Brueck P, Binckebank A, Atta J, Martin H, Gschaidmeier H,
et al: Activity of the ABL-tyrosine kinase inhibitor glivec(STI571) in Philadelphia chromosome positive acute lympho-

188

21.

22.

23.

24.

25.

26.

Ullmann AJ, et al: Current results on the use of imatinib mesylate in patients
blastic leukemia (PHþALL) relapsing after allogeneic stem celltransplantation (allo-SCT). Blood 2001; 98: abstract 2470
Pfeifer H, Wassmann B, Scheuring U, Binckebanck A, Atta J,
Brück P, Martin H, Bartmann M, Gschaidmeier H, Thiede C,
et al: STI571 (Glivec) in the treatment of patients with chronic
myeloid leukemia (CML) relapsing after allogeneic stem celltransplantation (allo SCT). Bone Marrow Transplantation 2002;
29 Supple 2: S34
Soiffer RJ, Galinsky I, DeAngelo D, Alyea EP, Antin JH, Restas
D, Stone RM: Imatinib mesylate (Gleevec) for disease relapse
following allogeneic bone marrow transplantation. Blood 2001;
98: abstract 1682
Ullmann AJ, Beck J, Kolbe K, Gschaidmeier H, Meinhardt PL,
Huber C, Fischer T: Clinical and laboratory evaluation of patients treated with STI-571 (GleevecTM ) after allogeneic andsyngeneic stem cell transplantation with relapsed Philadelphia
chromosome-positive leukemia. Blood 2001; 98: abstract 1685
Ullmann AJ, Beck J, Meinhardt P, Gschaidmeier H, Huber
C, Fischer T: STI-571 in patients with relapsed Philadelphia
chromosome-positive leukemia after allogeneic or syngeneic
SCT. Bone Marrow Transplantation 2002; 27 Supple 1: P433
Wassmann B, Pfeifer H, Scheuring U, Brueck P, Binckebank A,
Atta J, Martin H, Gschaidmeier H, Thiede C, Bornhauser M,
et al: Glivec (STI571) in the treatment of patients with chronic
myeloid leukemia (CML) relapsing in accelerated or blastic
phase after allogeneic stem cell transplantation. Blood 2001; 98:
abstract 588
Wassmann B, Pfeifer H, Scheuring U, Thiede C, Atta J, Klein
SA, Martin H, Bartmann M, Gschaidmeier H, Brück P, et al:Efﬁcacy of the ABL-tyrosine kinase inhibitor STI571 (Glivec) in
Philadelphia-chromosome positive acute lymphoblastic leukemia

27.

28.

29.

30.

31.

32.

(PhþAll) relapsing after allogeneic stem cell transplantation(Allo SCT). Bone Marrow Transplantation 2002; 29: Supple 2,
S6
Hess G, Reifenrath C, Friedrich-Freksa A, Beyer V, Naumann S,
Schuch B, Huber C, Fischer T, Decker HJ: Autologous transplantation of in vivo purged PBSC in CML: comparison of FISH,
cytogenetics, and PCR detection of Philadelphia chromosome inleukapheresis products. Cancer Genet Cytogenet 2000; 117: 1–
8Preudhomme C, Revillion F, Merlat A, Hornez L, Roumier C,
Duﬂos-Grardel N, Jouet JP, Cosson A, Peyrat JP, Fenaux P:
Detection of BCR-ABL transcripts in chronic myeloid leukemia(CML) using a ‘real time’ quantitative RT-PCR assay. Leukemia
1999; 13: 957–964
Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford
JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, et al:Efﬁcacy and safety of a speciﬁc inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;
344: 1031–1037
Kantarjian HM, Smith TL, O’Brien S, Beran M, Pierce S, Talpaz
M: Prolonged survival in chronic myelogenous leukemia after
cytogenetic response to interferon-alpha therapy. The Leukemia
Service. Ann Intern Med 1995; 122: 254–261
Emig M, Saussele S, Wittor H, Weisser A, Reiter A, Willer A,
Berger U, Hehlmann R, Cross NC, Hochhaus A: Accurate andrapid analysis of residual disease in patients with CML using
speciﬁc ﬂuorescent hybridization probes for real time quantitative RT-PCR. Leukemia 1999; 13: 1825–1832
Weisser A, La Rosée P, Burmeister T, et al: Sensitivity, quality
and comparability of bcr-abl quantiﬁcation by RT-PCR: resultsof an interlaboratory analysis. Blood 2001; 98: Abstract 1352