B-cell acute lymphoblastic leukemia, pediatric - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main pediatric B-ALL page for current regimens.
Last updated on 2024-07-23:17 regimens on this page
17 variants on this page
 
=Upfront induction therapy=
==Aminopterin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Farber et al. 1948	1947-1948 	Non-randomized pilot
Note: This regimen is of major historical interest, being one of the first published cancer chemotherapy experiments in man that led to an active non-clinical-trial intervention (to be distinguished from the trial of diopterin and teropterin published in Science in 1947). This agent is no longer available but was used clinically for several decades.
====Chemotherapy====
*Aminopterin
===References===
# Farber S, Mercer RD, Sylvester RF, Wolff JA, Diamond LK. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med. 1948 Jun 3;238(23):787-93. link to original article EuroPMC
==COMP==
COMP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Anderson et al. 1983	1977-1979 	Phase 3 (E-de-esc)	Modified LSA2-L2	Did not meet primary endpoint of FFS
Note: This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV once per day on days 3, 10, 17, 24
*Methotrexate (MTX) 180 mg/m2 IV push once on day 12, then 120 mg/m2 IV over 4 hours (total dose: 300 mg/m2)
====Glucocorticoid therapy====
*Prednisone (Sterapred) 15 mg/m2 (maximum dose of 15 mg) PO four times per day on days 3 to 30, then tapered off over days 31 to 37
37-day course
===References===
# Anderson JR, Wilson JF, Jenkin DT, Meadows AT, Kersey J, Chilcote RR, Coccia P, Exelby P, Kushner J, Siegel S, Hammond D. Childhood non-Hodgkin's lymphoma: the results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2). N Engl J Med. 1983 Mar 10;308(10):559-65. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence
Rivera et al. 1991	1984-02 to 1988-09 	Non-randomized part of RCT
Evans et al. 1998 	1988-1991 	Non-randomized part of RCT
====Chemotherapy====
*Cytarabine (Ara-C) 300 mg/m2 IV once per day on days 22, 25, 29
*Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 2, 8, +/- 15
*Asparaginase (Colaspase) 100,000 units IM once per day on days 3, 4, 6, 8, 10, 12, +/- 15, +/- 17, +/- 19
*Teniposide (Vumon) 200 mg/m2 IV once per day on days 22, 25, 29
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 (route not specified) once per day on days 1 to 29
42-day course
====Subsequent treatment====
*High-dose MTX
===References===
# Rivera GK, Raimondi SC, Hancock ML, Behm FG, Pui CH, Abromowitch M, Mirro J Jr, Ochs JS, Look AT, Williams DL, Murphy SB, Dahl GV, Kalwinsky DK, Evans WE, Kun LE, Simone JV, Crist WM. Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy. Lancet. 1991 Jan 12;337(8733):61-6. link to original article containds dosing details in manuscript EuroPMC
# Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med. 1998 Feb 19;338(8):499-505. link to original article EuroPMC
==Daunorubicin, Vincristine, Prednisolone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mathé et al. 1967 	Not reported 	Non-randomized 	 	
Halazun et al. 1974 (ALGB 6801)	1968-1971 	Phase 3 (E-RT-esc)	Vincristine & Prednisone	Did not meet primary endpoint of CR rate
Note: While the title and text of Mathé et al. 1967 described the use of prednisone, the treatment schema in Figure 2 reported prednisolone (with dosing); this dosing is replicated here.
====Chemotherapy====
*Daunorubicin (Cerubidine) 20 mg/m2 IV once per day on days 1 & 2
*Vincristine (Oncovin) 1.5 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 100 mg/m2 PO once per day on days 1 to 7
7-day cycles, continued until CR achieved or severe toxicity
===References===
#Mathé G, Hayat M, Schwarzenberg L, Amiel JL, Schneider M, Cattan A, Schlumberger JR, Jasmin C. Acute lymphoblastic leukaemia treated with a combination of prednisone, vincristine, and rubidomycin: Value of pathogen-free rooms. Lancet. 1967 Aug 19;2(7512):380-2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#ALGB 6801: Halazun JF, Wagner HR, Gaeta JF, Sinks LF. Proceedings: Daunorubicin cardiac toxicity in children with acute lymphocytic leukemia. Cancer. 1974 Feb;33(2):545-54. link to original article does not contain dosing details in manuscript EuroPMC
==Doxorubicin, L-asparaginase, Methotrexate, Vincristine, Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence
Vrooman et al. 2013 (DFCI 00-01)	2000-2004 	Non-randomized part of phase 3 trial
Note: the MTX dose reported in the manuscript appears to be erroneous, but is replicated here.
====Chemotherapy====
*Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 0 & 1
*Methotrexate (MTX) 4 mg/m2 IV once, given 8 to 24 hours after doxorubicin
*Asparaginase (Elspar) 25,000 units/m2 IM once (day not specified)
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 0, 7, 14, 21
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2/day IV or PO on days 0 to 28
====Supportive therapy====
*High-risk patients: Dexrazoxane (Zinecard) 300 mg/m2 IV once per day on days 0 & 1
29-day course
====Subsequent treatment====
*Intensification
===References===
#DFCI 00-01: Vrooman LM, Stevenson KE, Supko JG, O'Brien J, Dahlberg SE, Asselin BL, Athale UH, Clavell LA, Kelly KM, Kutok JL, Laverdière C, Lipshultz SE, Michon B, Schorin M, Relling MV, Cohen HJ, Neuberg DS, Sallan SE, Silverman LB. Postinduction dexamethasone and individualized dosing of Escherichia Coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study--Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol. 2013 Mar 20;31(9):1202-10. Epub 2013 Jan 28. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00165178
==Doxorubicin, Methotrexate, Vincristine, Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence
Clavell et al. 1986 (Protocol 81-01)	1981-1985 	Non-randomized
Note: the induction portion of this protocol begins on day 5. There was a methotrexate randomization which is not reported here.
====Chemotherapy====
*Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 5
*Methotrexate (MTX) 40 mg/m2 IV once on day 5
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 IV or PO once per day on days 5 to 33
28-day course
===References===
# Protocol 81-01: Clavell LA, Gelber RD, Cohen HJ, Hitchcock-Bryan S, Cassady JR, Tarbell NJ, Blattner SR, Tantravahi R, Leavitt P, Sallan SE. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med. 1986 Sep 11;315(11):657-63. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==L-Asparaginase, Vincristine, Dexamethasone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Veerman et al. 1996 (DCOG ALL-VI) 	1984-1988 	Non-randomized 	 	
Bostrom et al. 2003 (CCG-1922) 	1993-1995 	Phase 3 (E-switch-ic)	L-asparaginase, Vincristine, Prednisone 	Longer EFS
Mitchell et al. 2005 (UK MRC ALL97)	1997-2002 	Phase 3 (E-switch-ic)	L-asparaginase, Vincristine, Prednisolone	Longer EFS
Veerman et al. 2009 (DCOG ALL-9) 	1997-2004 	Non-randomized 	 	
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Chemotherapy====
*Asparaginase (Elspar) 6000 IU/m2 IV once per day on days 29, 33, 36, 40
*Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2.5 mg) IV once per day on days 1, 8, 15, 22, 29, 36
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 6 mg/m2/day PO on days 1 to 28, then tapered over days 29 to 42
42-day course
===References===
# DCOG ALL-VI: Veerman AJ, Hählen K, Kamps WA, Van Leeuwen EF, De Vaan GA, Solbu G, Suciu S, Van Wering ER, Van der Does-Van der Berg A; Dutch Childhood Oncology Group. High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia: results of protocol ALL VI from the Dutch Childhood Leukemia Study Group. J Clin Oncol. 1996 Mar;14(3):911-8. link to original article EuroPMC
# CCG-1922: Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME; Children's Cancer Group. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003 May 15;101(10):3809-17. Epub 2003 Jan 16. link to original article EuroPMC
# UK MRC ALL97: Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO; Medical Research Council Childhood Leukaemia Working Party. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005 Jun;129(6):734-45. link to original article EuroPMC NCT00003437
## Update: Vora A, Mitchell CD, Lennard L, Eden TO, Kinsey SE, Lilleyman J, Richards SM; Medical Research Council; National Cancer Research Network Childhood Leukaemia Working Party. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet. 2006 Oct 14;368(9544):1339-48. link to original article EuroPMC
# DCOG ALL-9: Veerman AJ, Kamps WA, van den Berg H, van den Berg E, Bökkerink JP, Bruin MC, van den Heuvel-Eibrink MM, Korbijn CM, Korthof ET, van der Pal K, Stijnen T, van Weel Sipman MH, van Weerden JF, van Wering ER, van der Does-van den Berg A; Dutch Childhood Oncology Group. Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004). Lancet Oncol. 2009 Oct;10(10):957-66. Epub 2009 Sep 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NTR460
==L-Asparaginase, Vincristine, Prednisolone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hann et al. 2000 (MRC UKALL XI) 	1990-1997 	Non-randomized part of RCT	 	
Mitchell et al. 2005 (UK MRC ALL97)	1997-2002 	Phase 3 (C) 	L-asparaginase, Vincristine, Dexamethasone	Shorter EFS
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The exact days of asparaginase administration were not described in Mitchell et al. 2005.
====Chemotherapy====
*Asparaginase (Elspar) 6000 mcg/m2 IM or SC once per day on days 1, 3, 5, 8, 10, 12, 15, 17, 19
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 7, 14, 21
====Glucocorticoid therapy====
*Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 28
====CNS therapy====
*Methotrexate (MTX) 12.5 mg/m2 IT once per day on days 1 & 8
28-day course
===References===
# MRC UKALL XI: Hann I, Vora A, Richards S, Hill F, Gibson B, Lilleyman J, Kinsey S, Mitchell C, Eden OB; UK Medical Research Council's Working Party on Childhood Leukaemia. Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. Leukemia. 2000 Mar;14(3):356-63. link to original article EuroPMC
# UK MRC ALL97: Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO; Medical Research Council Childhood Leukaemia Working Party. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005 Jun;129(6):734-45. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003437
## Update: Vora A, Mitchell CD, Lennard L, Eden TO, Kinsey SE, Lilleyman J, Richards SM; Medical Research Council; National Cancer Research Network Childhood Leukaemia Working Party. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet. 2006 Oct 14;368(9544):1339-48. link to original article EuroPMC
==L-Asparaginase, Vincristine, Prednisone==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Ortega et al. 1977 (CCG 101/143) 	1971 to not reported	Non-randomized (RT) 	 	
van der Does-van den Berg et al. 1989 (DCLSG ALL V)	1979-1982 	Phase 3 (C) 	DOLP 	Did not meet primary endpoint of EFS
Eden et al. 1991 (MRC UKALL VIII) 	1979-1982 	Phase 3 (C) 	DOLP 	Did not meet primary endpoint of EFS
Tubergen et al. 1993 (CCG-105) 	1983-1989 	Phase 3 (C) 	DOLP 	Not reported
Mahoney et al. 1998 (POG 9005) 	1991-1993 	Non-randomized part of phase 3 RCT	 	
Bostrom et al. 2003 (CCG-1922) 	1993-1995 	Phase 3 (C) 	L-asparaginase, Vincristine, Dexamethasone	Shorter EFS
Matloub et al. 2006 (CCG-1952) 	1996-2000 	Non-randomized part of phase 3 RCT	 	
Avramis et al. 2002 (CCG 1962) 	1997-1998 	Randomized (C) 	Pegaspargase, Vincristine, Prednisone 	Did not meet secondary endpoint of EFS
====Chemotherapy====
*Asparaginase (Elspar) 6000 units/m2 IM once per day on days 2, 5, 8, 12, 15, 19
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 5, 15, 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2/day (maximum dose of 60 mg/day) PO in three divided doses per day on days 1 to 28
28-day course
====Subsequent treatment====
*POG 9005: 6-MP & MTX; HDMTX/IVMP intensification versus 6-MP & MTX; LDMTX/IVMP intensification
*CCG-1952: Consolidation
===References===
# CCG 101/143: Ortega JA, Nesbit ME Jr, Donaldson MH, Hittle RE, Weiner J, Karon M, Hammond D. L-Asparaginase, vincristine, and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res. 1977 Feb;37(2):535-40. link to original article EuroPMC
# DCLSG ALL V: van der Does-van den Berg A, van Wering ER, Suciu S, Solbu G, van 't Veer MB, Rammeloo JA, de Koning J, van Zanen GE; Dutch Childhood Leukemia Study Group. Effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for standard risk childhood acute lymphocytic leukemia: results of a Dutch phase III study (ALL V); A report on behalf of the Dutch Childhood Leukemia Study Group (DCLSG). Am J Pediatr Hematol Oncol. 1989 Summer;11(2):125-33. EuroPMC
# MRC UKALL VIII: Eden OB, Lilleyman JS, Richards S, Shaw MP, Peto J. Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood). Br J Haematol. 1991 Jun;78(2):187-96. link to original article EuroPMC
# CCG-105: Tubergen DG, Gilchrist GS, O'Brien RT, Coccia PF, Sather HN, Waskerwitz MJ, Hammond GD. Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial. J Clin Oncol. 1993 Mar;11(3):527-37. link to original article EuroPMC
#POG 9005: Mahoney DH Jr, Shuster J, Nitschke R, Lauer SJ, Winick N, Steuber CP, Camitta B. Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group phase III trial. J Clin Oncol. 1998 Jan;16(1):246-54. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#CCG 1962: Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ, Ettinger AG, Ettinger LJ, Franklin J, Gaynon PS, Hilden JM, Lange B, Majlessipour F, Mathew P, Needle M, Neglia J, Reaman G, Holcenberg JS, Stork L. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study. Blood. 2002 Mar 15;99(6):1986-94. Erratum in: Blood 2002 Sep 1;100(5):1531. link to original article EuroPMC
# CCG-1922: Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME; Children's Cancer Group. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003 May 15;101(10):3809-17. Epub 2003 Jan 16. link to original article EuroPMC
# CCG-1952: Matloub Y, Lindemulder S, Gaynon PS, Sather H, La M, Broxson E, Yanofsky R, Hutchinson R, Heerema NA, Nachman J, Blake M, Wells LM, Sorrell AD, Masterson M, Kelleher JF, Stork LC; Children's Oncology Group. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. Blood. 2006 Aug 15;108(4):1165-73. Epub 2006 Apr 11. link to original article link to PMC article EuroPMC NCT00002744
==Mercaptopurine & Methotrexate==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Frei et al. 1958 (ALGB 01)	Not reported 	Randomized (E-switch-ic)	6-MP & MTX; alternate dosing	Did not meet endpoints
Frei et al. 1961 (ALGB 03)	1957-1960 	Randomized (E-esc) 	1. 6-MP2. MTX 	Did not meet endpoint of DOR
Frei et al. 1965 	Not reported 	Non-randomized 	 	
Note: this is one of the first combination regimens in hematology/oncology.
====Chemotherapy====
*Mercaptopurine (6-MP) 1.5 mg/kg PO twice per day
*Methotrexate (MTX) by the following age-based criteria:
**Less than 2 years old: 1.25 mg PO once per day
**2 to 10 years old: 2.5 mg PO once per day
**Older than 10 years old: 5 mg PO once per day
Continued indefinitely
===References===
# ALGB 01: Frei E 3rd, Holland JF, Schneiderman MA, Pinkel D, Selkirk G, Freireich EJ, Silver RT, Gold GL, Regelson W. A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood. 1958 Dec;13(12):1126-48. link to original article EuroPMC
# ALGB 03: Frei E, Freireich EJ, Gehan E, Pinkel D, Holland JF, Selawry O, Haurani F, Spurr CL, Hayes DM, James GW, Rothberg H, Sodee DB, Rundles RW, Schroeder LR, Hoogstraten B, Wolman IJ, Traggis DG, Cooper T, Gendel BR, Ebaugh F, Taylor R. Studies of Sequential and Combination Antimetabolite Therapy in Acute Leukemia: 6-Mercaptopurine and Methotrexate. Blood. 1961;18(4):431-454. link to original article dosing details in manuscript have been reviewed by our editors
# Frei E 3rd, Karon M, Levin RH, Freireich EJ, Taylor RJ, Hananian J, Selawry O, Holland JF, Hoogstraten B, Wolman IJ, Abir E, Sawitsky A, Lee S, Mills SD, Burgert EO Jr, Spurr CL, Patterson RB, Ebaugh FG, James GW 3rd, Moon JH. The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood. 1965 Nov;26(5):642-56. link to original article EuroPMC
==Mercaptopurine & Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fernbach et al. 1966	1960-1962 	Randomized (C)	Cyclophosphamide & Prednisone	Did not meet endpoint
====Chemotherapy====
*Mercaptopurine (6-MP) 2.5 mg/kg PO once per day on days 1 to 35
====Glucocorticoid therapy====
*Prednisone (Sterapred) 2.2 mg/kg/day (minimum dose of 20 mg and maximum dose of 60 mg) PO on days 1 to 28, then tapered over 7 days, divided into four doses per day
35-day course
===References===
# Fernbach DJ, Griffith KM, Haggard ME, Holcomb TM, Sutow WW, Vietti TJ, Windmiller J. Chemotherapy of acute leukemia in childhood: comparison of cyclophosphamide and mercaptopurine. N Engl J Med. 1966 Sep 1;275(9):451-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Vincristine & Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Halazun et al. 1974 (ALGB 6801)	1968-1971 	Phase 3 (C)	Daunorubicin, Vincristine, Prednisone	Did not meet primary endpoint of CR rate
====Chemotherapy====
*Vincristine (Oncovin)
====Glucocorticoid therapy====
*Prednisone (Sterapred)
===References===
#ALGB 6801: Halazun JF, Wagner HR, Gaeta JF, Sinks LF. Proceedings: Daunorubicin cardiac toxicity in children with acute lymphocytic leukemia. Cancer. 1974 Feb;33(2):545-54. link to original article does not contain dosing details in manuscript EuroPMC
=Consolidation after upfront therapy=
==Mercaptopurine & Methotrexate==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Evans et al. 1986	1979-1982 	Randomized (E-switch-ooc)	WBRT, then 6-MP & MTX; conventional dosing	Not reported
Note: although this is a randomized trial, the report focuses on this arm, which includes HD-MTX, and not the comparison.
====Preceding treatment====
*L-Asparaginase, Vincristine, Prednisone induction
====Chemotherapy====
*Mercaptopurine (6-MP) 50 mg/m2 PO once per day on days 1 to 42
*Methotrexate (MTX) 25 mg/m2 PO once per day on days 1, 8, 15, 22, 29, 36
*Methotrexate (MTX) as follows:
**Cycle 1: 1000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15
**Cycles 2 to 14: 1000 mg/m2 IV continuous infusion over 24 hours, started on day 15
42-day cycle for 20 cycles
===References===
# Evans WE, Crom WR, Abromowitch M, Dodge R, Look AT, Bowman WP, George SL, Pui CH. Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia: identification of a relation between concentration and effect. N Engl J Med. 1986 Feb 20;314(8):471-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Maintenance after upfront therapy=
==Methotrexate monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Selawry & Holland 1965 (ALGB 6313)	1963 	Randomized (E-switch-ic)	MTX; oral 	Longer RFS
Burgert et al. 1969 (ALGB 6311) 	Not reported 	Randomized (E-switch-ic)	MTX; oral 	Did not meet endpoint
====Preceding treatment====
*Vincristine & Prednisone induction
====Chemotherapy====
*Methotrexate (MTX) 30 mg/m2 IM once per day on days 1 & 4 (twice per week)
7-day cycles
===References===
# ALGB 6313: Selawry OS, Holland JF; Acute Leukemia Group B. New treatment schedule with improved survival in childhood leukemia: intermittent parenteral vs daily oral administration of methotrexate for maintenance of induced remission. JAMA. 1965 Oct 4;194(1):75-81. link to original article congaints dosing details in manuscript EuroPMC
# ALGB 6311: Burgert EO, Valvo F, Petzold G, Holland JF; Acute Leukemia Group B. Acute lymphocytic leukemia in children: maintenance therapy with methotrexat administered intermittently. JAMA. 1969 Feb 3;207(5):923-8. link to original article EuroPMC
=Relapsed or refractory=
==Cyclophosphamide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Fernbach et al. 1962	1959-1960 	Non-randomized
Note: This was the dosing used in the final n=26 patients enrolled.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 5 mg/kg PO once per day
Continued indefinitely
===References===
# Fernbach DJ, Sutow WW, Thurman WG, Vietti TJ. Clinical evaluation of cyclophosphamide: a new agent for the treatment of children with acute leukemia. JAMA. 1962 Oct 6;182:30-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Daunorubicin & Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence
Holton et al. 1969	Not reported 	Non-randomized
====Chemotherapy====
*Daunorubicin (Cerubidine) 25 mg/m2 IV push once per day on days 1 to 3, 8 to 10, 15, 22, (29), (36)
====Glucocorticoid therapy====
*Prednisone (Sterapred) 20 mg/m2 PO three times per day on days 1 to 28, then tapered off over days 29 to 35
6-week course
===References===
# Holton CP, Vietti TJ, Nora AH, Donaldson MH, Stuckey WJ Jr, Watkins WL, Lane DM. Clinical study of daunomycin and prednisone for induction of remission in children with advanced leukemia. N Engl J Med. 1969 Jan 23;280(4):171-4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==L-Asparaginase, Vincristine, Prednisone==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Anderson et al. 1981	Not reported in abstract	Phase 3 (C)	L-Asparaginase, Vindesine, Prednisone	Did not meet primary endpoint of ORR
Note: There are no dosing details in the abstract; the full manuscript is not available for review online.
====Chemotherapy====
*Asparaginase (Elspar)
*Vincristine (Oncovin)
====Glucocorticoid therapy====
*Prednisone (Sterapred)
===References===
# Anderson J, Krivit W, Chilcote R, Pyesmany A, Chard R, Hammond D. Comparison of the therapeutic response of patients with childhood acute lymphoblastic leukemia in relapse to vindesine versus vincristine in combination with prednisone and L-asparaginase: a phase III trial. Cancer Treat Rep. 1981 Nov-Dec;65(11-12):1015-9. dosing details not available in abstract EuroPMC
Category:B-cell acute lymphoblastic leukemia regimens
Category:Acute lymphoblastic leukemias
Category:Historical regimens
Category:Disease-specific pages
Category:Pediatric hematologic neoplasms