Acute myeloid 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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. 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 pediatric AML page for current regimens.

8 regimens on this page
8 variants on this page


Upfront induction therapy

7+3d (low-dose)

7+3d: 7 days of cytarabine + 3 days of daunorubicin

Regimen

Study Dates of enrollment Evidence
Nesbit et al. 1994 (CCG 251) 1979-1983 Non-randomized part of RCT

Chemotherapy

Two courses

References

  1. CCG 251: Nesbit ME Jr, Buckley JD, Feig SA, Anderson JR, Lampkin B, Bernstein ID, Kim TH, Piomelli S, Kersey JH, Coccia PF, O'Reilly RC, August C, Thomas ED, Hammond GD; Children's Cancer Group. Chemotherapy for induction of remission of childhood acute myeloid leukemia followed by marrow transplantation or multiagent chemotherapy: a report from the Childrens Cancer Group. J Clin Oncol. 1994 Jan;12(1):127-35. link to original article PubMed
    1. Pooled update: Smith FO, Alonzo TA, Gerbing RB, Woods WG, Arceci RJ; Children's Cancer Group. Long-term results of children with acute myeloid leukemia: a report of three consecutive phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891. Leukemia. 2005 Dec;19(12):2054-62. link to original article PubMed

Cytarabine, Doxorubicin, Vincristine, Prednisolone

Regimen

Study Dates of enrollment Evidence
Weinstein et al. 1980 1976-1979 Non-randomized

Chemotherapy

  • Cytarabine (Ara-C) as follows:
    • Course 1: 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
    • Course 2: 100 mg/m2/day IV continuous infusion over 5 days, started on day 1 (total dose: 500 mg/m2)
  • Doxorubicin (Adriamycin) as follows:
    • Course 1: 30 mg/m2 IV once per day on days 1 to 3
    • Course 2: 30 mg/m2 IV once per day on days 1 & 2
  • Vincristine (Oncovin) as follows:
    • Course 1: 1.5 mg/m2 IV once per day on days 1 & 5
    • Course 2: 1.5 mg/m2 IV once on day 1

Glucocorticoid therapy

2 courses

References

  1. Weinstein HJ, Mayer RJ, Rosenthal DS, Camitta BM, Coral FS, Nathan DG, Frei E 3rd. Treatment of acute myelogenous leukemia in children and adults. N Engl J Med. 1980 Aug 28;303(9):473-8. link to original article contains dosing details in manuscript PubMed

DAT

DAT: Daunorubicin, Ara-C (Cytarabine), Thioguanine
TAD: Thioguanine, Ara-C (Cytarabine), Daunorubicin
TAD9: Thioguanine, Ara-C (Cytarabine), Daunorubicin over 9 days

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Steuber et al. 1991 (POG 8101) 1977-1981 Phase 3 (C) VADx Seems to have superior CR rate

Chemotherapy

7-day course

References

  1. POG 8101: Steuber CP, Civin C, Krischer J, Culbert S, Ragab A, Ruymann FB, Ravindranath Y, Leventhal B, Wilkinson R, Vietti TJ. A comparison of induction and maintenance therapy for acute nonlymphocytic leukemia in childhood: results of a Pediatric Oncology Group study. J Clin Oncol. 1991 Feb;9(2):247-58. link to original article contains dosing details in manuscript PubMed

DCTER

DCTER: Dexamethasone, Cytarabine, Thioguanine, Etoposide, Rubidomycin (Daunomycin)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Wells et al. 1994 (CCG 213) 1986-1989 Phase 3 (E-esc) 7+3d; standard-dose Did not meet efficacy endpoints
Woods et al. 1996 (CCG 2891) 1989-1993 Phase 3 (E-esc) DCTER; standard timing Superior DFS
Lange et al. 2007 (CCG 2961) 1996-2002 Phase 3 (C) IdaDCTER/DCTER Did not meet co-primary endpoints of RR/DFS

Glucocorticoid therapy

  • Dexamethasone (Decadron) by the following age-based criteria:
    • Younger than 3 years old: 2 mg/m2 (route not specified) three times per day
    • 3 years old and older: 0.2 mg/kg/day (route not specified) split into 3 doses

Chemotherapy

  • Cytarabine (Ara-C) by the following age-based criteria:
    • Younger than 3 years old: 6.7 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 26.8 mg/kg)
    • 3 years old and older: 200 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 800 mg/m2)
  • Thioguanine (Tabloid) by the following age-based criteria:
    • Younger than 3 years old: 1.65 mg/kg PO twice per day
    • 3 years old and older: 50 mg/m2 PO twice per day
  • Etoposide (Vepesid) by the following age-based criteria:
    • Younger than 3 years old: 3.3 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 13.2 mg/kg)
    • 3 years old and older: 100 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 400 mg/m2)
  • Daunorubicin (Cerubidine) by the following age-based criteria:
    • Younger than 3 years old: 0.67 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2.68 mg/kg)
    • 3 years old and older: 20 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 80 mg/m2)

4-day course

References

  1. CCG 213: Wells RJ, Woods WG, Buckley JD, Odom LF, Benjamin D, Bernstein I, Betcher D, Feig S, Kim T, Ruymann F, Smithson W, Srivastava A, Tannous R, Buckley CM, Whitt JK, Wolff L, Lampkin BC; Children's Cancer Group. Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Childrens Cancer Group study. J Clin Oncol. 1994 Nov;12(11):2367-77. link to original article PubMed
    1. Pooled update: Smith FO, Alonzo TA, Gerbing RB, Woods WG, Arceci RJ; Children's Cancer Group. Long-term results of children with acute myeloid leukemia: a report of three consecutive phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891. Leukemia. 2005 Dec;19(12):2054-62. link to original article PubMed
  2. CCG 2961: Lange BJ, Smith FO, Feusner J, Barnard DR, Dinndorf P, Feig S, Heerema NA, Arndt C, Arceci RJ, Seibel N, Weiman M, Dusenbery K, Shannon K, Luna-Fineman S, Gerbing RB, Alonzo TA. Outcomes in CCG-2961, a Children's Oncology Group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group. Blood. 2008 Feb 1;111(3):1044-53. Epub 2007 Nov 13. link to original article link to PMC article PubMed NCT00002798
  3. CCG 2891: Woods WG, Kobrinsky N, Buckley JD, Lee JW, Sanders J, Neudorf S, Gold S, Barnard DR, DeSwarte J, Dusenbery K, Kalousek D, Arthur DC, Lange BJ. Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: a report from the Children's Cancer Group. Blood. 1996 Jun 15;87(12):4979-89. link to original article contains dosing details in manuscript PubMed
    1. Pooled update: Smith FO, Alonzo TA, Gerbing RB, Woods WG, Arceci RJ; Children's Cancer Group. Long-term results of children with acute myeloid leukemia: a report of three consecutive phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891. Leukemia. 2005 Dec;19(12):2054-62. link to original article PubMed

D-ZAPO

D-ZAPO: Daunomycin, 5-Azacytidine, Ara-C (Cytarabine), Prednisone, Oncovin (Vincristine)

Regimen

Study Dates of enrollment Evidence
Baehner et al. 1979 (CCG 241) NR in abstract Non-randomized part of RCT

References

  1. CCG 241: Baehner RL, Bernstein ID, Sather H, Higgins G, McCreadie S, Chard RL, Hammond D. Improved remission induction rate with D-ZAPO but unimproved remission duration with addition of immunotherapy to chemotherapy in previously untreated children with ANLL. Med Pediatr Oncol. 1979;7(2):127-39. link to original article PubMed

Mercaptopurine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Heyn et al. 1960 1955-1957 Phase 3 (C) 6-MP & Azaserine Did not meet efficacy endpoints

Note: This was the first RCT of the Acute Leukemia Chemotherapy Cooperative Study Group A (ALCCSGA), subsequently renamed the Children's Cancer Group (CCG).

Chemotherapy

Continued for at least 28 days

References

  1. Heyn RM, Brubaker CA, Burchenal JH, Cramblett HG, Wolff JA; Acute Leukemia Chemotherapy Cooperative Study Group A. The comparison of 6-mercaptopurine with the combination of 6-mercaptopurine and azaserine in the treatment of acute leukemia in children: results of a cooperative study. Blood. 1960 Mar;15:350-9. link to original article contains dosing details in manuscript PubMed

PATCO

PATCO: Prednisone, Ara-C (Cytarabine), Thioguanine, Cyclophosphamide, Oncovin (Vincristine)

Regimen

Study Dates of enrollment Evidence
Chard et al. 1978 (CCG 102) NR in abstract Non-randomized

References

  1. CCG 102: Chard RL Jr, Finklestein JZ, Sonley MJ, Nesbit M, McCreadie S, Weiner J, Sather H, Hammond GD. Increased survival in childhood acute nonlymphocytic leukemia after treatment with prednisone, cytosine arabinoside, 6-thioguanine, cyclophosphamide, and oncovin (PATCO) combination chemotherapy. Med Pediatr Oncol. 1978;4(3):263-73. link to original article PubMed

Relapsed or refractory, salvage therapy

FLAG-DNX

FLAG-DNX: FLudarabine, Ara-C (Cytarabine), G-CSF, DauNoXome (Daunorubicin liposomal)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Kaspers et al. 2013 (I-BFM-SG 2001/01) 2001-2009 Phase 3 (E-esc) FLAG Seems to have superior CR rate (secondary endpoint)

Seems to have superior day 28 bone marrow status (primary endpoint)

Note: this regimen was studied in patients up to 21 years of age. Liposomal daunorubicin (DaunoXome) is discontinued.

Chemotherapy

Growth factor therapy

2 cycles

Subsequent treatment

References

  1. I-BFM-SG 2001/01: Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. link to original article contains dosing details in manuscript PubMed NCT00186966