Modifications to induction therapy decrease risk of early death in infants with acute lymphoblastic leukemia treated on Children's Oncology Group P9407

Background: Infants (<366 days of age) with acute lymphoblastic leukemia (ALL) have a poor prognosis. Most treatment failures occur within 6-9 months of diagnosis, primarily from relapse. Procedure: The Children's Oncology Group P9407 study was designed to test if early intensified treatment would improve outcome for infants with ALL. Due to a significant number of early deaths (<90 days from enrollment), Induction therapy was amended three times. Cohorts 1+2 (n=68), received identical Induction therapy except for reduced daunorubicin dose in Cohort 2. Cohort 3 (n=141) received prednisone (40mg/m²/day) instead of dexamethasone (10mg/m²/day) and short infusion daunorubicin (30 minutes) instead of continuous infusion (48 hours), as well as additional supportive care measures throughout therapy. Results: Early deaths occurred in 17/68 (25%) infants in Cohorts 1+2 and 8/141 (5.7%) infants in Cohort 3 (P<0.0001). Among infants ≤90 days of age at diagnosis, early death occurred in 10/17 (58.8%) in Cohorts 1+2 and 4/27 (14.8%) in Cohort 3 (P=0.006). Among infants >90 days of age at diagnosis, early death occurred in 7/51 (13.7%) in Cohorts 1+2 and 4/114 (3.5%) in Cohort 3 (P=0.036). Bacterial, viral, and fungal infections were more common in Cohorts 1+2 versus Cohort 3. Conclusions: Early morbidity and mortality for infants with ALL were reduced by substitution of prednisone (40mg/m²/day) for dexamethasone (10mg/m²/day), the delivery of daunorubicin over 30 minutes instead of a continuous infusion for 48 hours, and the provision of more specific supportive care measures.