Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Retrospective Multinational Study

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Abstract

PURPOSE: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials.

PATIENTS AND METHODS: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome.

RESULTS: With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction.

CONCLUSION: MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.

Details

Authors
Organisations
External organisations
  • University of Milano-Bicocca
  • Tel-Aviv University
  • Princess Maxima Center for Pediatric Oncology/Hematology
  • National University of Singapore
  • University of Newcastle upon Tyne
  • St Jude Children´s Research Hospital, Memphis
  • University of Tennessee
  • University of Kiel
  • University Medical Center Schleswig-Holstein Campus Kiel
  • Medical University of Vienna
  • Paris Diderot University
  • University of Padova
  • Great Ormond Street Hospital. London
  • Charles University in Prague
  • University Hospital Motol
  • Dana-Farber Cancer Institute
  • Boston Children's Hospital
  • Saitama Children's Medical Center
  • MacKay Memorial Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)770-779
Number of pages10
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number10
Publication statusPublished - 2019 Apr 1
Publication categoryResearch
Peer-reviewedYes