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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main pediatric AML page for current regimens.
Last updated on 2024-07-23:8 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====
*Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
*Daunorubicin (Cerubidine) 30 mg/m2 IV once per day on days 1 to 3
Two courses
===References===
# 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 EuroPMC
## 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 EuroPMC
==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====
*Prednisolone (Millipred) 40 mg/m2 IV every 12 hours on days 1 to 5
2 courses
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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 higher CR rate
====Chemotherapy====
*Daunorubicin (Cerubidine) 45 mg/m2 IV push once per day on days 1 to 3
*Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
*Thioguanine (Tabloid) 100 mg/m2 PO once per day on days 1 to 7
7-day course
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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	Longer DFS (primary endpoint)DFS36: 55% vs 37%(HR not reported, p=0.0002)
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===
# 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 EuroPMC
## 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 EuroPMC
# 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 EuroPMC NCT00002798
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
==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)	Not reported in abstract	Non-randomized part of RCT
Note: The original manuscript was not available online for review.
====Chemotherapy====
*Daunorubicin (Cerubidine)
*Azacitidine (Vidaza)
*Cytarabine (Ara-C)
*Vincristine (Oncovin)
====Glucocorticoid therapy====
*Prednisone (Sterapred)
===References===
# 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 dosing details not available in abstract EuroPMC
==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====
*Mercaptopurine (6-MP) 2.5 mg/kg PO once per day
Continued for at least 28 days
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==PATCO==
PATCO: Prednisone, Ara-C (Cytarabine), Thioguanine, Cyclophosphamide, Oncovin (Vincristine)
===Regimen===
Study 	Dates of enrollment 	Evidence
Chard et al. 1978 (CCG 102)	Not reported in abstract	Non-randomized
Note: The original manuscript was not available online for review.
====Glucocorticoid therapy====
*Prednisone (Sterapred)
====Chemotherapy====
*Cytarabine (Ara-C)
*Thioguanine (Tabloid)
*Cyclophosphamide (Cytoxan)
*Vincristine (Oncovin)
===References===
# 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 dosing details not available in abstract EuroPMC
=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 higher CR rate (secondary endpoint)Seems to have better 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====
*Fludarabine (Fludara) 30 mg/m2 IV once per day on days 1 to 5, given second
*Cytarabine (Ara-C) 2000 mg/m2 IV once per day on days 1 to 5, given fourth, 4 hours after start of fludarabine
*Daunorubicin liposomal (DaunoXome) as follows:
**Cycle 1: 60 mg/m2 IV once per day on days 1, 3, 5, given third
====Growth factor therapy====
*Filgrastim (Neupogen) 200 mcg/m2 (route not specified) once per day on days 0 to 5, given first
2 cycles
====Subsequent treatment====
*CYVE or Cytarabine & Thioguanine consolidation, as a bridge to allogeneic HSCT
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00186966
Category:Acute myeloid leukemia regimens
Category:Historical regimens
Category:Disease-specific pages
Category:Acute leukemias
Category:Pediatric hematologic neoplasms