B-cell acute lymphoblastic leukemia - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 B-ALL page for current regimens.

Last updated on 2024-07-23:
11 regimens on this page
13 variants on this page


Upfront induction therapy

Cyclophosphamide, Doxorubicin, L-asparaginase, Vincristine, Prednisolone

Regimen

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

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • G-CSF 200 mcg/m2 IV once per day on days 12 to 26

35-day course

Subsequent treatment

  • Consolidation I (see paper for details)

References

  1. 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 dosing details in manuscript have been reviewed by our editors PubMed


Idarubicin, L-Asparaginase, Vincristine, Prednisone

Regimen

Study Dates 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

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

Glucocorticoid therapy

35-day course

References

  1. 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00483132


L-Asparaginase, Vincristine, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Henderson et al. 1979 (CALGB 7113) 1971-1976 Non-randomized
Gottlieb et al. 1984 (CALGB 7612) 1976-1980 Randomized (C) DOLP Inferior CR rate

Note: The asparaginase dosing shown here was that after a mid-protocol amendment due to excess toxicity.

Chemotherapy

Glucocorticoid therapy

28-day course

References

  1. 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 dosing details in manuscript have been reviewed by our editors PubMed
  2. 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


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-MP
2. MTX
Did not meet endpoint of DOR

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

  1. 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
  2. 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


Prednisolone monotherapy

Regimen variant #1

Study Dates of enrollment Evidence
Shanbrom & Miller 1962 Not reported Non-randomized

Glucocorticoid therapy

10-day course


Regimen variant #2

Study Dates of enrollment Evidence
Shanbrom & Miller 1962 Not reported Non-randomized

Glucocorticoid therapy

10-day course

References

  1. 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 dosing details in manuscript have been reviewed by our editors PubMed


Prednisone monotherapy

Regimen variant #1

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

Glucocorticoid therapy

One course


Regimen variant #2

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

Glucocorticoid therapy

One course

References

  1. 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 dosing details in manuscript have been reviewed by our editors PubMed


Late intensification

POMP

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

Regimen

Study Dates of enrollment Evidence
Bodey et al. 1976 1970-03 to 1973-05 Non-randomized, fewer than 20 pts

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

Chemotherapy

Glucocorticoid therapy

One course

References

  1. 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 dosing details in manuscript have been reviewed by our editors PubMed


Relapsed or refractory

BCG vaccine monotherapy

Regimen

Study Dates of enrollment Evidence
Mathé et al. 1969 Not reported Non-randomized

Immunotherapy

References

  1. 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


Pentostatin monotherapy

Regimen

Study Dates of enrollment Evidence
Prentice et al. 1981 Not reported Pilot

Chemotherapy

5- to 7-day course

References

  1. 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 dosing details in manuscript have been reviewed by our editors 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

Supportive therapy

One course

References

  1. 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 Dates of enrollment Evidence Efficacy
O'Brien et al. 2012 (RALLY) 2007 to not reported Phase 2 (RT) ORR: 35%

Chemotherapy

7-day cycles

References

  1. 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00495079