title: Modifications to induction therapy decrease risk of early death in infants with acute lymphoblastic leukemia treated on Children's Oncology Group P9407.
abstract: 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.
  
  
  METHODS
  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 (40 mg/m(2)/day) instead of dexamethasone (10 mg/m(2)/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 (40 mg/m(2)/day) for dexamethasone (10 mg/m(2)/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.
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. salzerw@mail.nih.gov
authors.forename: Wanda L
authors.initials: WL
authors.lastname: Salzer
authors.forename: Tamekia L
authors.initials: TL
authors.lastname: Jones
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Hilden
authors.forename: Naomi
authors.initials: N
authors.lastname: Winick
authors.forename: Stephen
authors.initials: S
authors.lastname: Hunger
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Bruce
authors.initials: B
authors.lastname: Camitta
authors.forename: ZoAnn E
authors.initials: ZE
authors.lastname: Dreyer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
chemical_list: D003907:Dexamethasone; D011239:Prednisolone; D003630:Daunorubicin