Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials

Cornelia Eckert, Catriona Parker, Anthony V. Moorman, Julie AE Irving, Renate Kirschner-Schwabe, Stefanie Groeneveld-Krentz, Tamas Révész, Peter Hoogerbrugge, Jeremy Hancock, Rosemary Sutton, Guenter Henze, Christiane Chen-Santel, Andishe Attarbaschi, Jean Pierre Bourquin, Lucie Sramkova, Martin Zimmermann, Shekhar Krishnan, Arend von Stackelberg, Vaskar Saha

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT). Methods: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses. Results: Outcomes of patients were comparable in ALLR3 and ALL-REZ BFM 2002. The event-free survival of B-cell precursor (BCP) and T-cell ALL (T-ALL) was 22.6% and 26.2% (P = 0.94), respectively, and the overall survival (OS) was 32.6% and 28.2% (P = 0.11), respectively. Induction failures (38%) were associated with deletions of NR3C1 (P = 0.002) and BTG1 (P = 0.03) in BCP-ALL. The disease-free survival (DFS) and OS in patients with good vs poor MRD responses were 57.4% vs 22.6% (P < 0.0001) and 57.8% vs 32.0% (P = 0.0004), respectively. For BCP- and T-ALL, the post-SCT DFS and OS were 42.1% and 56.8% (P = 0.26) and 51.6% and 55.4% (P = 0.67), respectively. The cumulative incidences of post-SCT relapse for BCP- and T-ALL were 36.9% and 17.8% (P = 0.012) and of death were 10.7% and 25.5% (P = 0.013), respectively. Determinants of outcomes after SCT were acute graft versus host disease, pre-SCT MRD (≥10−3), HR cytogenetics and TP53 alterations in BCP-ALL. Conclusion: Improvements in outcomes for HR ALL relapses require novel compounds in induction therapy to improve remission rates and immune targeted therapy after induction to maintain remission after SCT. Trial registration: ALLR3: NCT00967057; ALL REZ-BFM 2002: NCT00114348

Original languageEnglish (US)
Pages (from-to)175-189
Number of pages15
JournalEuropean Journal of Cancer
Volume151
DOIs
StatePublished - Jul 2021
Externally publishedYes

Keywords

  • Acute lymphoblastic leukaemia
  • High-risk
  • Minimal residual disease
  • Outcomes
  • Stem cell transplantation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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