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 by Beverly J. Lange, Franklin O. Smith, James Feusner, Dorothy R. Barnard, Patricia Dinndorf, Stephen Feig, Nyla A. Heerema, Carola Arndt, Robert J. Arceci, Nita Seibel, Margie Weiman, Kathryn Dusenbery, Kevin Shannon, Sandra Luna-Fineman, Robert B. Gerbing, and Todd A. Alonzo Blood Volume 111(3):1044-1053 February 1, 2008 ©2008 by American Society of Hematology

Course 1 and Course 2: IdaDCTER is idarubicin 5 mg/m2 per day infused more than half an hour daily, cytarabine 200 mg/m2 /day and etoposide 100 mg/m2 per day both as continuous 96-hour infusions (CI), oral thioguanine 100 mg/m2 per day, and dexamethasone 6 ... Course 1 and Course 2: IdaDCTER is idarubicin 5 mg/m2 per day infused more than half an hour daily, cytarabine 200 mg/m2 /day and etoposide 100 mg/m2 per day both as continuous 96-hour infusions (CI), oral thioguanine 100 mg/m2 per day, and dexamethasone 6 mg/m2on days 0 to 3. On days 10 to 13, daunorubicin 20 mg/m2 day CI replaces idarubicin. Course 2: FAMP is fludarabine monophosphate, 10.5 mg/m2 loading dose, then 30.5 mg/m2 per 24 hours for a total of 48 hours, followed by beginning Ara-C 390 mg/m2 loading dose and 2400 mg/m2 per 24 hours continuous infusion for 72 hours and idarubicin 12 mg/m2 per day infused more than half an hour on days 0, 1, and 2 at 12.0 mg/m2 per day. G-CSF, 5 μg/kg per day, initiated in patients with less than 5% residual leukemic blasts in day 14 ± 1 marrow and continued until neutrophil recovery. HidAC is cytarabine 3 g/m2 as 3-hour infusions at hours 0 to 3, 12 to 15, 24 to 27, and 36 to 39 on days 0 and 7 followed by Escherichia coli L-asparaginase 6000 units/m2 intramuscularly at hour 42 given on days 1 and 8. Marrow transplantation cytoreduction consists of 16 doses of busulfan at 40 mg/m2 orally every 6 hours on days −9, −8, −7, and −6 and cyclophosphamide 50 mg/kg IV more than one hour on days −5,−4,−3, and −2; interleukin-2 is 9 × 106 IU/m2 per day CI day 0 to 3 and 1.6 × 106 IU/m2 per day on CI days 8 to 17. Central nervous system prophylaxis was intrathecal cytarabine on days 0 and 10 of course 1 and course 2 regimen A and weekly times 3 following recovering of counts after HidAC.14,61 In courses 1 and 2, G-CSF, 5 μg/m2 per day was started 48 hours after completion of chemotherapy and continued until the neutrophil count was more than 1500 × 109/L. Beverly J. Lange et al. Blood 2008;111:1044-1053 ©2008 by American Society of Hematology

Event-free survival and overall survival in CCG-2961. Event-free survival and overall survival in CCG-2961. Kaplan-Meier plot of survival (OS) and event-free survival (EFS) from time on study. Beverly J. Lange et al. Blood 2008;111:1044-1053 ©2008 by American Society of Hematology

Outcomes in CCG-2961 according to donor availability. Outcomes in CCG-2961 according to donor availability. (A) Kaplan-Meier plot of OS and disease-free survival (DFS) from the time of entry to course 3 for those with and without matched related donors for marrow transplantation. (B) OS and DFS for those patients with favorable cytogenetics according to donor status. Beverly J. Lange et al. Blood 2008;111:1044-1053 ©2008 by American Society of Hematology

Kaplan-Meier plot of OS according to time of study entry. Beverly J. Lange et al. Blood 2008;111:1044-1053 ©2008 by American Society of Hematology