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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main B-ALL page for current regimens.

11 regimens on this page 13 variants on this page

Upfront induction therapy

Aminopterin monotherapy

Regimen

Study	Years 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 PubMed

COMP

COMP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Anderson et al. 1983	1977-1979	Phase 3 (E-de-esc)	Modified LSA₂-L₂	Seems not superior

Chemotherapy

Glucocorticoid therapy

Prednisone (Sterapred)

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 PubMed

Cyclophosphamide, Doxorubicin, L-Asparaginase, Vincristine, Prednisolone

Regimen

Study	Years of enrollment	Evidence
Takeuchi et al. 2002 (JALSG-ALL93)	1993-1997	Non-randomized

Chemotherapy

Glucocorticoid therapy

Prednisolone (Millipred)

References

JALSG-ALL93: Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S, Kuriyama K, Ohtake S, Yagasaki F, Murakami H, Asou N, Ino T, Okamoto T, Usui N, Nishimura M, Shinagawa K, Fukushima T, Taguchi H, Morii T, Mizuta S, Akiyama H, Nakamura Y, Ohshima T, Ohno R. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia. 2002 Jul;16(7):1259-66. link to original article PubMed

Cytarabine, Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone

Regimen

Study	Years of enrollment	Evidence
Pieters et al. 2007 (Interfant-99)	1999-2005	Non-randomized portion of RCT

Preceding treatment

Prednisone pre-phase

Chemotherapy

Glucocorticoid therapy

Dexamethasone (Decadron)

Subsequent treatment

MARAM consolidation

References

Interfant-99: Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, Hovi L, LeBlanc T, Szczepanski T, Ferster A, Janka G, Rubnitz J, Silverman L, Stary J, Campbell M, Li CK, Mann G, Suppiah R, Biondi A, Vora A, Valsecchi MG. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007 Jul 21;370(9583):240-250. link to original article PubMed NCT00015873

Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence
Rivera et al. 1991	NR in abstract	Non-randomized portion of RCT
Evans et al. 1998	1988-1991	Non-randomized portion of RCT

Chemotherapy

Glucocorticoid therapy

Prednisone (Sterapred)

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 PubMed
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 PubMed

Daunorubicin, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Halazun et al. 1974 (ALGB 6801)	1968-1971	Phase 3 (E-RT-esc)	Vincristine & Prednisone	Did not meet primary endpoint of CR rate

Chemotherapy

Glucocorticoid therapy

Prednisone (Sterapred)

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 PubMed
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 PubMed

Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence
Vrooman et al. 2013 (DFCI 00-01)	2000-2004	Non-randomized portion 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 contains dosing details in manuscript PubMed NCT00165178

Doxorubicin, Methotrexate, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence
Clavell et al. 1986	1981-1985	Non-randomized

Chemotherapy

Glucocorticoid therapy

Prednisone (Sterapred)

References

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 PubMed

Idarubicin, L-Asparaginase, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hunault et al. 2004 (GOELAL02)	1994-1998	Phase 3 (C)	Idarubicin, L-asparaginase, Vincristine, Prednisone; oral prednisone	Did not meet primary endpoint of response rate

Chemotherapy

Glucocorticoid therapy

Prednisone (Sterapred) IV

References

GOELAL02: Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F, Lamy T, Pignon B, Jouet JP, Garidi R, Caillot D, Berthou C, Guyotat D, Sadoun A, Sotto JJ, Lioure B, Casassus P, Solal-Celigny P, Stalnikiewicz L, Audhuy B, Blanchet O, Baranger L, Béné MC, Ifrah N; GOELAMS (Groupe Ouest-Est des Leucémies Airguës et Maladies du Sang) Group. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood. 2004 Nov 15;104(10):3028-37. Epub 2004 Jul 15. link to original article PubMed NCT00483132

L-Asparaginase, Vincristine, Dexamethasone

Regimen

Study	Years 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	Superior EFS
Mitchell et al. 2005 (UK MRC ALL97)	1997-2002	Phase 3 (E-switch-ic)	L-asparaginase, Vincristine, Prednisolone	Superior EFS
Veerman et al. 2009 (DCOG ALL-9)	1997-2004	Non-randomized

Chemotherapy

Glucocorticoid therapy

Dexamethasone (Decadron)

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 PubMed
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 PubMed
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 PubMed NCT00003437
1. 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 PubMed
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 PubMed NTR460

L-Asparaginase, Vincristine, Prednisolone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hann et al. 2000 (MRC UKALL XI)	1990-1997	Non-randomized portion of RCT
Mitchell et al. 2005 (UK MRC ALL97)	1997-2002	Phase 3 (C)	L-asparaginase, Vincristine, Dexamethasone	Inferior EFS

Chemotherapy

Glucocorticoid therapy

Prednisolone (Millipred)

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 PubMed
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 PubMed NCT00003437
1. 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 PubMed

L-Asparaginase, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ortega et al. 1977 (CCG 101/143)	1971-NR	Non-randomized (RT)
Henderson et al. 1979 (CALGB 7113)	1971-1976	Non-randomized
Gottlieb et al. 1984 (CALGB 7612)	1976-1980	Randomized (C)	DOLP	Inferior CR rate
van der Does-van den Berg et al. 1989 (DCLSG ALL V)	1979-1982	Phase 3 (C)	DOLP	Seems not superior
Eden et al. 1991 (MRC UKALL VIII)	1979-1982	Phase 3 (C)	DOLP	Seems not superior
Tubergen et al. 1993 (CCG-105)	1983-1989	Phase 3 (C)	DOLP	Not reported
Bostrom et al. 2003 (CCG-1922)	1993-1995	Phase 3 (C)	L-asparaginase, Vincristine, Dexamethasone	Inferior EFS
Matloub et al. 2006 (CCG-1952)	1996-2000	Non-randomized portion of phase 3 RCT

Chemotherapy

Glucocorticoid therapy

Prednisone (Sterapred)

28-day course

Subsequent treatment

CCC-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 PubMed
CALGB 7113: Henderson ES, Scharlau C, Cooper MR, Haurani FI, Silver RT, Brunner K, Carey RW, Falkson G, Blom J, Nawabi IV, Levine AS, Bank A, Cuttner J, Cornwell GG 3rd, Henry P, Nissen NI, Wiernik PH, Leone L, Wohl H, Rai K, James GW, Weinberg V, Glidewell O, Holland JF. Combination chemotherapy and radiotherapy for acute lymphocytic leukemia in adults: results of CALGB protocol 7113. Leuk Res. 1979;3(6):395-407. link to original article PubMed
CALGB 7612: Gottlieb AJ, Weinberg V, Ellison RR, Henderson ES, Terebelo H, Rafla S, Cuttner J, Silver RT, Carey RW, Levy RN, Hutchinson JL, Raich P, Cooper MR, Wiernik P, Anderson JR, Holland JF. Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by Cancer and Leukemia Group B. Blood. 1984 Jul;64(1):267-74. link to original article PubMed
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. PubMed
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 PubMed
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 PubMed
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 PubMed
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 PubMed NCT00002744

Mercaptopurine & Methotrexate

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Frei et al. 1958 (ALGB 01)	NR	Randomized (E-switch-ic)	6-MP & MTX; alternate dosing	Seems not superior
Frei et al. 1961 (ALGB 03)	1957-1960	Randomized (E-esc)	1. 6-MP 2. MTX	Seems not superior
Frei et al. 1965	NR	Non-randomized

Note: this is one of the first combination regimens in hematology/oncology.

Chemotherapy

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 PubMed
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
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 PubMed

Mercaptopurine & Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Fernbach et al. 1966	1960-1962	Randomized (C)	Cyclophosphamide & Prednisone	Seems not superior

Chemotherapy

Mercaptopurine (6-MP)

Glucocorticoid therapy

Prednisone (Sterapred)

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 PubMed

Prednisolone monotherapy

Regimen

Study	Years of enrollment	Evidence
Shanbrom & Miller 1962	NR	Non-randomized

Glucocorticoid therapy

Prednisolone (Millipred)

References

Shanbrom E, Miller S. Critical evaluation of massive steroid therapy of acute leukemia. N Engl J Med. 1962 Jun 28;266:1354-8. link to original article PubMed

Prednisone monotherapy

Regimen

Study	Years of enrollment	Evidence
Granville et al. 1958	1955-1956	Non-randomized

Glucocorticoid therapy

Prednisone (Sterapred)

References

Granville NB, Rubio F Jr, Unugur A, Schulman E, Dameshek W. Treatment of acute leukemia in adults with massive doses of prednisone and prednisolone. N Engl J Med. 1958 Jul 31;259(5):207-13. link to original article PubMed

Consolidation after upfront therapy

Mercaptopurine & Methotrexate

Regimen

Study	Years 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

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 PubMed

Late intensification

POMP

POMP: Purinethol (Mercaptopurine), Oncovin (Vincristine), Methotrexate, Prednisone

Regimen

Study	Years of enrollment	Evidence
Bodey et al. 1976	NR in abstract	Non-randomized, <20 pts

Note: POMP is still used in maintenance settings; this is marked historic because it is late intensification.

Chemotherapy

Glucocorticoid therapy

Prednisone (Sterapred)

References

Bodey GP, Freireich EJ, Gehan E, McCredie KB, Rodriguez V, Gutterman J, Burgess MA. Late intensification therapy for acute leukemia in remission: chemotherapy and immunotherapy. JAMA. 1976 Mar 8;235(10):1021-5. link to original article PubMed

Maintenance after upfront therapy

Methotrexate monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Selawry & Holland 1965 (ALGB 6313)	1963	Randomized (E-switch-ic)	MTX; oral	Superior RFS
Burgert et al. 1969 (ALGB 6311)	NR	Randomized (E-switch-ic)	MTX; oral	Seems not superior

Preceding treatment

Vincristine & Prednisone induction

Chemotherapy

Methotrexate (MTX) IV or IM

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 PubMed
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 PubMed

Relapsed or refractory

Bacillus Calmette-Guérin (BCG) monotherapy

Regimen

Study	Years of enrollment	Evidence
Mathé et al. 1969	NR in abstract	Non-randomized

Immunotherapy

Bacillus Calmette-Guérin (BCG)

References

Mathé G, Amiel JL, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. Lancet. 1969 Apr 5;1(7597):697-9. link to original article PubMed

Cyclophosphamide monotherapy

Regimen

Study	Years of enrollment	Evidence
Fernbach et al. 1962	NR in abstract	Non-randomized

Chemotherapy

Cyclophosphamide (Cytoxan)

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 PubMed

Daunorubicin & Prednisone

Regimen

Study	Years of enrollment	Evidence
Holton et al. 1969	NR	Non-randomized

Chemotherapy

Daunorubicin (Cerubidine)

Glucocorticoid therapy

Prednisone (Sterapred)

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 PubMed

L-Asparaginase, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Anderson et al. 1981	NR in abstract	Phase 3 (C)	L-Asparaginase, Vindesine, Prednisone	Seems not superior

Chemotherapy

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. PubMed

Pentostatin monotherapy

Regimen

Study	Years of enrollment	Evidence
Prentice et al. 1981	NR in abstract	Pilot

Chemotherapy

Pentostatin (Nipent)

References

Prentice HG, Russell NH, Lee N, Ganeshaguru K, Blacklock H, Piga A, Smyth JF, Hoffbrand AV. Therapeutic selectivity of and predication of response to 2'-deoxycoformycin in acute leukaemia. Lancet. 1981 Dec 5;2(8258):1250-4. link to original article PubMed

TBI, then auto HSCT

TBI: Total Body Irradiation

Regimen

Study	Evidence
McGovern et al. 1959	Pilot

Note: This is of historic interest and likely the first reported use of autologous HSCT in the treatment of malignancy.

Radiotherapy

Total body irradiation

References

McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. link to original article PubMed

Vincristine liposomal monotherapy

Regimen

Study	Years of enrollment	Evidence	Efficacy
O'Brien et al. 2012 (RALLY)	2007-NR	Phase 2 (RT)	ORR: 35%

Chemotherapy

Vincristine liposomal (Marqibo) 2.25 mg/m² IV over 60 minutes once per day on days 1, 8, 15, 22

28-day cycles

References

RALLY: O'Brien S, Schiller G, Lister J, Damon L, Goldberg S, Aulitzky W, Ben-Yehuda D, Stock W, Coutre S, Douer D, Heffner LT, Larson M, Seiter K, Smith S, Assouline S, Kuriakose P, Maness L, Nagler A, Rowe J, Schaich M, Shpilberg O, Yee K, Schmieder G, Silverman JA, Thomas D, Deitcher SR, Kantarjian H. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013 Feb 20;31(6):676-83. Epub 2012 Nov 19. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00495079

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 The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[B-cell acute lymphoblastic leukemia|main B-ALL page]] for current regimens.
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 10: / Line 9: @@
 <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
 {{TOC limit|limit=3}}
 =Upfront induction therapy=
 ==Aminopterin monotherapy {{#subobject:1cf0b5|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:be57ed|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 27: / Line 24: @@
 |-
 |}
-''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 [http://science.sciencemag.org/content/106/2764/619.long published in Science in 1947]). This agent is no longer available but was used clinically for several decades.''
+''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 [http://science.sciencemag.org/content/106/2764/619.long published in Science in 1947]). This agent is no longer available but was used clinically for several decades.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Aminopterin]]
+</div></div>
 ===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. [https://doi.org/10.1056/NEJM194806032382301 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18860765 PubMed]
 ==COMP {{#subobject:2ec876|Regimen=1}}==
 COMP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:0ecc0a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 52: / Line 49: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cyclophosphamide (Cytoxan)]]
@@ Line 58: / Line 56: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===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. [https://doi.org/10.1056/NEJM198303103081003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6338381 PubMed]
 ==Cyclophosphamide, Doxorubicin, L-Asparaginase, Vincristine, Prednisolone {{#subobject:6edd1f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:0f2246|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
@@ Line 74: / Line 72: @@
 |-
 |}
-''Unlikely to be completed, here for historic context only.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cyclophosphamide (Cytoxan)]]
@@ Line 82: / Line 80: @@
 ====Glucocorticoid therapy====
 *[[Prednisolone (Millipred)]]
+</div></div>
 ===References===
 # '''JALSG-ALL93:''' Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S, Kuriyama K, Ohtake S, Yagasaki F, Murakami H, Asou N, Ino T, Okamoto T, Usui N, Nishimura M, Shinagawa K, Fukushima T, Taguchi H, Morii T, Mizuta S, Akiyama H, Nakamura Y, Ohshima T, Ohno R. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia. 2002 Jul;16(7):1259-66. [https://doi.org/10.1038/sj.leu.2402526 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12094249 PubMed]
 ==Cytarabine, Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone {{#subobject:5a7eda|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:245098|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 99: / Line 96: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[B-cell_acute_lymphoblastic_leukemia#Prednisone_monotherapy|Prednisone pre-phase]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]]
@@ Line 108: / Line 108: @@
 ====Glucocorticoid therapy====
 *[[Dexamethasone (Decadron)]]
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *MARAM consolidation
+</div></div>
 ===References===
 # '''Interfant-99:''' Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, Hovi L, LeBlanc T, Szczepanski T, Ferster A, Janka G, Rubnitz J, Silverman L, Stary J, Campbell M, Li CK, Mann G, Suppiah R, Biondi A, Vora A, Valsecchi MG. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007 Jul 21;370(9583):240-250. [https://doi.org/10.1016/s0140-6736(07)61126-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/17658395 PubMed] NCT00015873
 ==Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone {{#subobject:177f43|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:2c8cee|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 131: / Line 132: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]]
@@ Line 139: / Line 141: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *High-dose MTX
+</div></div>
 ===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. [https://doi.org/10.1016/0140-6736(91)90733-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1670723 PubMed]
 # 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. [https://doi.org/10.1056/NEJM199802193380803 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9468466 PubMed]
 ==Daunorubicin, Vincristine, Prednisone {{#subobject:h1huh5|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:h1cc9b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 163: / Line 166: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Daunorubicin (Cerubidine)]]
@@ Line 168: / Line 172: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===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. [https://doi.org/10.1016/s0140-6736(67)92004-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4166329/ PubMed]
 #'''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. [https://doi.org/10.1002/1097-0142(197402)33:2%3C545::aid-cncr2820330233%3E3.0.co;2-m link to original article] [https://pubmed.ncbi.nlm.nih.gov/4521474/ PubMed]
 ==Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Prednisone {{#subobject:h1h91c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:hbn19b|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 186: / Line 190: @@
 |}
 ''Note: the MTX dose reported in the manuscript appears to be erroneous, but is replicated here.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
 *[[Methotrexate (MTX)]] 4 mg/m<sup>2</sup> IV once, '''given 8 to 24 hours after doxorubicin'''
@@ Line 194: / Line 198: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day IV or PO on days 0 to 28
 ====Supportive therapy====
 *High-risk patients: [[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0 & 1
 '''29-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Intensification
+</div></div>
 ===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. [https://doi.org/10.1200/jco.2012.43.2070 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3595424/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23358966/ PubMed] NCT00165178
 ==Doxorubicin, Methotrexate, Vincristine, Prednisone {{#subobject:96590c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:dee4bf|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 221: / Line 221: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Doxorubicin (Adriamycin)]]
@@ Line 227: / Line 228: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===References===
 # 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. [https://doi.org/10.1056/NEJM198609113151101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2943992 PubMed]
 ==Idarubicin, L-Asparaginase, Vincristine, Prednisone {{#subobject:54jbs9|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3y2de2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 248: / Line 248: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-''Unlikely to be completed, here for historic context only.''
 ====Chemotherapy====
 *[[Idarubicin (Idamycin)]]
@@ Line 256: / Line 255: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]] IV
+</div></div>
 ===References===
 #'''GOELAL02:''' Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F, Lamy T, Pignon B, Jouet JP, Garidi R, Caillot D, Berthou C, Guyotat D, Sadoun A, Sotto JJ, Lioure B, Casassus P, Solal-Celigny P, Stalnikiewicz L, Audhuy B, Blanchet O, Baranger L, Béné MC, Ifrah N; GOELAMS (Groupe Ouest-Est des Leucémies Airguës et Maladies du Sang) Group. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood. 2004 Nov 15;104(10):3028-37. Epub 2004 Jul 15. [https://doi.org/10.1182/blood-2003-10-3560 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15256423/ PubMed] NCT00483132
 ==L-Asparaginase, Vincristine, Dexamethasone {{#subobject:54ea09|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:4c9de2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 296: / Line 293: @@
 |-
 |}
-''Unlikely to be completed, here for historic context only.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Asparaginase (Elspar)]]
@@ Line 302: / Line 299: @@
 ====Glucocorticoid therapy====
 *[[Dexamethasone (Decadron)]]
+</div></div>
 ===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. [https://doi.org/10.1200/JCO.1996.14.3.911 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622039 PubMed]
@@ Line 309: / Line 306: @@
 ## '''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. [https://doi.org/10.1016/s0140-6736(06)69558-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17046466 PubMed]
 # '''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. [https://doi.org/10.1016/s1470-2045(09)70228-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19747876 PubMed] NTR460
 ==L-Asparaginase, Vincristine, Prednisolone {{#subobject:65692a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:4af0d5|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 333: / Line 329: @@
 |-
 |}
-''Unlikely to be completed, here for historic context only.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Asparaginase (Elspar)]]
@@ Line 339: / Line 335: @@
 ====Glucocorticoid therapy====
 *[[Prednisolone (Millipred)]]
+</div></div>
 ===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. [https://doi.org/10.1038/sj.leu.2401704 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10720126 PubMed]
 # '''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. [https://doi.org/10.1111/j.1365-2141.2005.05509.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/15952999 PubMed] 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. [https://doi.org/10.1016/s0140-6736(06)69558-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17046466 PubMed]
 ==L-Asparaginase, Vincristine, Prednisone {{#subobject:d039d8|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a4174a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 404: / Line 399: @@
 |-
 |}
-''Unlikely to be completed, here for historic context only.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Asparaginase (Elspar)]]
@@ Line 410: / Line 405: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
 '''28-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *CCC-1952: Consolidation
+</div></div>
 ===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. [https://cancerres.aacrjournals.org/content/37/2/535.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/264412 PubMed]
@@ Line 425: / Line 420: @@
 # '''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. [http://www.bloodjournal.org/content/101/10/3809.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/12531809 PubMed]
 # '''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. [https://doi.org/10.1182/blood-2005-12-011809 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1895867/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16609069/ PubMed] NCT00002744
 ==Mercaptopurine & Methotrexate {{#subobject:6366a6|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:1fc958|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 456: / Line 450: @@
 |}
 ''Note: this is one of the first combination regimens in hematology/oncology.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mercaptopurine (6-MP)]]
 *[[Methotrexate (MTX)]]
+</div></div>
 ===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. [http://www.bloodjournal.org/content/13/12/1126.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/13596417 PubMed]
 # '''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. [http://www.bloodjournal.org/content/18/4/431.short link to original article]
 # 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. [http://www.bloodjournal.org/content/26/5/642.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/5321112 PubMed]
 ==Mercaptopurine & Prednisone {{#subobject:f609f5|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c637f6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 482: / Line 476: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mercaptopurine (6-MP)]]
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===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. [https://doi.org/10.1056/NEJM196609012750901 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5917939 PubMed]
 ==Prednisolone monotherapy {{#subobject:5d40b1|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:b66a94|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 503: / Line 497: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Glucocorticoid therapy====
 *[[Prednisolone (Millipred)]]
+</div></div>
 ===References===
 # Shanbrom E, Miller S. Critical evaluation of massive steroid therapy of acute leukemia. N Engl J Med. 1962 Jun 28;266:1354-8. [https://doi.org/10.1056/NEJM196206282662603 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13911203 PubMed]
 ==Prednisone monotherapy {{#subobject:5eeb7e|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:07e67b|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 521: / Line 516: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===References===
 # Granville NB, Rubio F Jr, Unugur A, Schulman E, Dameshek W. Treatment of acute leukemia in adults with massive doses of prednisone and prednisolone. N Engl J Med. 1958 Jul 31;259(5):207-13. [https://doi.org/10.1056/NEJM195807312590502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13566450 PubMed]
 =Consolidation after upfront therapy=
 ==Mercaptopurine & Methotrexate {{#subobject:7a01b3|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:752310|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 545: / Line 541: @@
 |}
 ''Note: although this is a randomized trial, the report focuses on this arm, which includes HD-MTX, and not the comparison.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#L-Asparaginase.2C_Vincristine.2C_Prednisone|L-Asparaginase, Vincristine, Prednisone]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mercaptopurine (6-MP)]]
 *[[Methotrexate (MTX)]]
+</div></div>
 ===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. [https://doi.org/10.1056/NEJM198602203140803 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3456079 PubMed]
 =Late intensification=
 ==POMP {{#subobject:31219|Regimen=1}}==
 POMP: '''<u>P</u>'''urinethol (Mercaptopurine), '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:93b1b3|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 570: / Line 568: @@
 |}
 ''Note: POMP is still used in maintenance settings; this is marked historic because it is late intensification.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mercaptopurine (6-MP)]]
@@ Line 576: / Line 575: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===References===
 # Bodey GP, Freireich EJ, Gehan E, McCredie KB, Rodriguez V, Gutterman J, Burgess MA. Late intensification therapy for acute leukemia in remission: chemotherapy and immunotherapy. JAMA. 1976 Mar 8;235(10):1021-5. [https://jamanetwork.com/journals/jama/fullarticle/344212 link to original article] [https://pubmed.ncbi.nlm.nih.gov/946184 PubMed]
 =Maintenance after upfront therapy=
 ==Methotrexate monotherapy {{#subobject:478e97|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:028121|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 603: / Line 602: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Vincristine_.26_Prednisone_88|Vincristine & Prednisone]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Methotrexate (MTX)]] IV or IM
+</div></div>
 ===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. [https://jamanetwork.com/journals/jama/article-abstract/656675 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5896942 PubMed]
 # '''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. [https://jamanetwork.com/journals/jama/article-abstract/343520 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4303512 PubMed]
 =Relapsed or refractory=
 ==Bacillus Calmette-Guérin (BCG) monotherapy {{#subobject:e05416|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:637e03|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 626: / Line 627: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Bacillus Calmette-Guérin (BCG)]]
+</div></div>
 ===References===
 # Mathé G, Amiel JL, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. Lancet. 1969 Apr 5;1(7597):697-9. [https://doi.org/10.1016/s0140-6736(69)92648-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4182654 PubMed]
 ==Cyclophosphamide monotherapy {{#subobject:cd166d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:047e6a|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 644: / Line 646: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cyclophosphamide (Cytoxan)]]
+</div></div>
 ===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. [https://jamanetwork.com/journals/jama/article-abstract/331608 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13892445 PubMed]
 ==Daunorubicin & Prednisone {{#subobject:aa10e0|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:19d9c6|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 662: / Line 665: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Daunorubicin (Cerubidine)]]
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===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. [https://doi.org/10.1056/NEJM196901232800401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5248383 PubMed]
 ==L-Asparaginase, Vincristine, Prednisone {{#subobject:87ybf2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a61pz6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 686: / Line 690: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Asparaginase (Elspar)]]
@@ Line 691: / Line 696: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]]
+</div></div>
 ===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. [https://pubmed.ncbi.nlm.nih.gov/6945911 PubMed]
 ==Pentostatin monotherapy {{#subobject:aa19e0|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:19d2c6|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 708: / Line 712: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Pentostatin (Nipent)]]
+</div></div>
 ===References===
 # Prentice HG, Russell NH, Lee N, Ganeshaguru K, Blacklock H, Piga A, Smyth JF, Hoffbrand AV. Therapeutic selectivity of and predication of response to 2'-deoxycoformycin in acute leukaemia. Lancet. 1981 Dec 5;2(8258):1250-4. [https://doi.org/10.1016/S0140-6736(81)91491-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6118669 PubMed]
 ==TBI, then auto HSCT {{#subobject:1a2735|Regimen=1}}==
 TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:635694|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 725: / Line 730: @@
 |-
 |}
-''This is of historic interest and likely the first reported use of autologous HSCT in the treatment of malignancy.''
+''Note: This is of historic interest and likely the first reported use of autologous HSCT in the treatment of malignancy.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
 *[[External_beam_radiotherapy|Total body irradiation]]
+</div></div>
 ===References===
 # McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. [https://doi.org/10.1056/NEJM195904022601401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13644566 PubMed]
 ==Vincristine liposomal monotherapy {{#subobject:f19406|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:18f662|Variant=1}}===
 {| class="wikitable sortable" style="width: 80%; text-align:center;"
@@ Line 746: / Line 752: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Vincristine liposomal (Marqibo)]] 2.25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22
 '''28-day cycles'''
+</div></div>
 ===References===
 # '''RALLY:''' O'Brien S, Schiller G, Lister J, Damon L, Goldberg S, Aulitzky W, Ben-Yehuda D, Stock W, Coutre S, Douer D, Heffner LT, Larson M, Seiter K, Smith S, Assouline S, Kuriakose P, Maness L, Nagler A, Rowe J, Schaich M, Shpilberg O, Yee K, Schmieder G, Silverman JA, Thomas D, Deitcher SR, Kantarjian H. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013 Feb 20;31(6):676-83. Epub 2012 Nov 19. [https://doi.org/10.1200/jco.2012.46.2309 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979201/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23169518 PubMed] NCT00495079
 [[Category:B-cell acute lymphoblastic leukemia regimens]]
 [[Category:Historical regimens]]

Difference between revisions of "B-cell acute lymphoblastic leukemia - historical"

Revision as of 01:22, 9 February 2023

Upfront induction therapy

Aminopterin monotherapy

Regimen

Chemotherapy

References

COMP

Regimen

Chemotherapy

Glucocorticoid therapy

References

Cyclophosphamide, Doxorubicin, L-Asparaginase, Vincristine, Prednisolone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Cytarabine, Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone

Regimen

Preceding treatment

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

References

Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

References

Daunorubicin, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

Supportive therapy

Subsequent treatment

References

Doxorubicin, Methotrexate, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Idarubicin, L-Asparaginase, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

L-Asparaginase, Vincristine, Dexamethasone

Regimen

Chemotherapy

Glucocorticoid therapy

References

L-Asparaginase, Vincristine, Prednisolone

Regimen

Chemotherapy

Glucocorticoid therapy

References

L-Asparaginase, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

References

Mercaptopurine & Methotrexate

Regimen

Chemotherapy

References

Mercaptopurine & Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Prednisolone monotherapy

Regimen

Glucocorticoid therapy