Trisomy of leukemic cell chromosomes 4 and 10 identifies children with B- progenitor cell acute lymphoblastic leukemia with a very low risk of treatment failure: A Pediatric Oncology Group Study

Academic Article

Abstract

  • To account for the superior prognosis of hyperdiploid, B-progenitor acute lymphoblastic leukemia (ALL), we investigated the influence of trisomy in 1021 children ≥1 year old by recursive partitioning analysis. The patients were treated according to a stratified, randomized study testing antimetabolite-based therapies. Trisomies of several individual chromosomes were associated with a better prognosis in a univariate statistical analysis. Of greater importance, trisomy of both chromosomes 4 and 10 identified a subgroup of patients (n = 180) with an extremely favorable 4-year event-free survival (EFS). Combined trisomy of chromosomes 4 and 10 retained its prognostic significance after stratification of patients by DNA index, age, and leukocyte count. Among patients with a DNA index greater than 1.16, patients with trisomies of both chromosomes 4 and 10 had a 4-year EFS of 96.6% (n = 161, SE = 3.8%), whereas patients with neither or only one of these trisomies had a 4-year EFS of 70.4% (n = 73, SE = 11.5%). All 19 patients with a DNA index ≤1.16 but with trisomies of chromosomes 4 and 10 remain in remission, suggesting that favorable chromosome trisomy dominates in a situation in which the cellular DNA content of ≤1.16 predicts a less favorable outcome. We conclude that combined trisomy of chromosomes 4 and 10 independently predicts EFS among children with B-progenitor ALL. Patients within the B-progenitor group who have this feature (about 20% of those with clonal abnormalities) are likely to be cured with antimetabolite-based chemotherapy-an approach that should produce few significant late effects.
  • Published In

  • Blood  Journal
  • Digital Object Identifier (doi)

    Author List

  • Harris MB; Shuster JJ; Carroll A; Look AT; Borowitz MJ; Crist WM; Nitschke R; Pullen J; Steuber CP; Land VJ
  • Start Page

  • 3316
  • End Page

  • 3324
  • Volume

  • 79
  • Issue

  • 12