Extended vincristine and dexamethasone pulse therapy may not be necessary for children with TCF3-PBX1 positive acute lymphoblastic leukaemia

Br J Haematol. 2022 Nov;199(4):587-596. doi: 10.1111/bjh.18437. Epub 2022 Sep 16.

Abstract

The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3-PBX1 positive acute lymphoblastic leukaemia (ALL) remains uncertain. We conducted non-inferiority analysis of 263 newly diagnosed TCF3-PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG-ALL-2015 clinical trial from January 2015 to December 2019 (ChiCTR-IPR-14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow-up of 4.2 years, the 5-year event-free survival (EFS) and 5-year overall survival (OS) in the control group were 90.1% (95% confidence interval [CI] 85.1-95.4) and 94.7% (95% CI, 90.9-98.6) comparable to those in the experimental group 89.2% (95% CI 84.1-94.7) and 95.6% (95% CI 91.8-99.6), respectively. Non-inferiority was established as a one-sided 95% upper confidence bound for the difference in probability of 5-year EFS was 0.003, and that for 5-year OS was 0.01 by as-treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3-PBX1 positive ALL.

Keywords: TCF3-PBX1; CCCG-ALL-2015; acute lymphoblastic leukaemia; vincristine plus dexamethasone pulses.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Basic Helix-Loop-Helix Transcription Factors
  • Child
  • Dexamethasone / therapeutic use
  • Humans
  • Oncogene Proteins, Fusion
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  • Vincristine / therapeutic use

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Dexamethasone
  • Oncogene Proteins, Fusion
  • PBX1 protein, human
  • Pre-B-Cell Leukemia Transcription Factor 1
  • TCF3 protein, human
  • TCF3-PBX1 fusion protein, human
  • Vincristine