Effect Of Intensification Of Induction Ii Chemotherapy And Liberalization Of Stem Cell Donor Source On Outcome For Children With High Risk Acute Myeloid Leukemia: A Report From The Children'S Oncology Group.

10002 Background: Patients with residual acute myeloid leukemia (AML) after induction fare poorly. The recently completed AAML1031 Phase III clinical trial intensified Induction II chemotherapy, altered the stem cell transplant (SCT) conditioning regimen, and liberalized SCT donor source criteria. We sought to test whether these practice changes improved clinical outcomes. Methods: Patients on AAML0531 and AAML1031, sequential Phase III trials for AML with shared high risk features of both > 15% residual blasts by morphology and ≥ 0.1% minimal residual disease (MRD) by flow cytometry with uninformative cytogenetics or high risk cytogenetic features (-7 or -5/5q-) were included. Gemtuzmab exposed and patients with high allelic ratio FLT3 ITD were excluded. Patients were observed from the start of Induction II through last available follow up. Induction II chemotherapy (ADE or AraC/Mito) was the exposure of interest. Disease free and overall survival (DFS, OS) were the primary outcomes. Standard descriptive statistics were used to compare patient characteristics and secondary outcomes; Kaplan Meier analyses were used to evaluate DFS/OS. Results: A total of 47 patients from AAML0531 (ADE) and 95 patients from AAML1031 (AraC/Mito) were included and did not differ in baseline characteristics. Five year DFS ±2SE was 17.5 ± 11.4 for ADE and 23.9 ± 8.8 for AraC/Mito, p = 0.528. Five year OS was 38.1 ± 14.2 for ADE and 33.3 ± 10.7 for AraC/Mito, p = 0.364. End of Induction II disease response and MRD did not differ between ADE and AraC/Mito. Patients receiving ADE had a higher probability of neutrophil recovery (74% vs 53%, p = 0.019) and recovered neutrophils a median of 7 days more quickly (27 vs 34 days), p = < 0.001. ADE patients also had fewer inpatient hospital days (28 days versus 32 days, p = 0.002). The percentage of patients receiving SCT did not differ, 34% vs 44%, p = 0.253 and post-SCT outcomes did not differ. Conclusions: The intensification of Induction II chemotherapy, change in SCT conditioning regimen, and liberalization of SCT donor source was not associated with improved clinical outcomes. Intensification of Induction II was associated with increased hematologic toxicity and length of stay. These data do not support the intensification of Induction II chemotherapy with AraC/Mitoxantrone. Clinical trial information: NCT01371981.