Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3)

Pediatr Blood Cancer. 2015 Mar;62(3):419-26. doi: 10.1002/pbc.25322. Epub 2014 Nov 14.

Abstract

Background: Infants with acute lymphoblastic leukemia (ALL) present with aggressive disease and a poor prognosis. Early relapse within 6-9 months of diagnosis is common. Approximately 75% of infants have MLL-rearranged (MLL-R) ALL with event free survival (EFS) ranging from 20% to 30%. Children's Oncology Group (COG) P9407 used shortened (46 weeks), intensified therapy to address early relapse and poor EFS.

Procedure: P9407 therapy was modified three times for induction toxicity resulting in three cohorts of therapy. One hundred forty-seven infants were enrolled in the third cohort.

Results: We report an overall 5-year EFS and OS of 42.3 ± 6% and 52.9 ± 6.5% respectively. Poor prognostic factors included age ≤90 days at diagnosis, MLL-R ALL and white cell count ≥50,000/μl. For infants ≤90 days of age, the 5-year EFS was 15.5 ± 10.1% and 48.5 ± 6.7% for those >90 days (P < 0.0001). Among infants >90 days of age, 5-year EFS rates were 43.8 ± 8% for MLL-R versus 69.1 ± 13.6% for MLL-germline ALL (P < 0.0001).

Conclusions: Age ≤90 days at diagnosis was the most important prognostic factor. Despite shortened therapy with early intensification, EFS remained less than 50% overall in MLL-R ALL.

Keywords: COG P9407; Intensified therapy without SCT; infant ALL.

Publication types

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

MeSH terms

  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Rearrangement
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Recurrence
  • Risk Factors
  • Stem Cell Transplantation
  • Survival Rate

Substances

  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase