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

Pediatr Blood Cancer. 2012 Nov;59(5):834-9. doi: 10.1002/pbc.24132. Epub 2012 Apr 5.

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.

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 (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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Daunorubicin / administration & dosage
  • Daunorubicin / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Prednisolone / administration & dosage
  • Prednisolone / adverse effects
  • Retrospective Studies
  • Survival Rate
  • Time Factors

Substances

  • Dexamethasone
  • Prednisolone
  • Daunorubicin