Haematopoietic stem cell transplantation after reduced intensity conditioning in children and adolescents with chronic myeloid leukaemia: A prospective multicentre trial of the I-BFM Study Group

Br J Haematol. 2024 Jul;205(1):268-279. doi: 10.1111/bjh.19535. Epub 2024 May 27.

Abstract

This prospective multicentre trial evaluated the safety and the efficacy of a thiotepa/melphalan-based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) in children and adolescents with chronic myeloid leukaemia (CML) in chronic phase (CP). Thirty-two patients were transplanted from matched siblings or matched unrelated donors. In 22 patients, HSCT was performed due to insufficient molecular response or loss of response to first- or second-generation tyrosine kinase inhibitor (TKI), with pretransplant BCR::ABL1 transcripts ranging between 0.001% and 33%. The protocol included a BCR::ABL1-guided intervention with TKI retreatment in the first year and donor lymphocyte infusions (DLI) in the second-year post-transplant. All patients engrafted. The 1-year transplant-related mortality was 3% (confidence interval [CI]: 0%-6%). After a median follow-up of 6.3 years, 5-year overall survival and event-free survival are 97% (CI: 93%-100%) and 91% (CI: 79%-100%) respectively. The current 5-year leukaemia-free survival with BCR::ABL1 <0.01% is 97% (CI: 88%-100%) and the current TKI- and DLI-free survival is 95% (CI: 85%-100%). The incidence of chronic graft-versus-host disease (GvHD) was 32%, being severe in four patients (13%). At last follow-up, 31 patients are GvHD-free and have stopped immunosuppression. RIC HSCT following pretreatment with TKI is feasible and effective in children and adolescents with CP-CML with an excellent disease-free and TKI-free survival.

Keywords: allogeneic stem cell transplantation; children and adolescents; chronic myeloid leukaemia; reduced intensity conditioning.

Publication types

  • Multicenter Study
  • Clinical Trial

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / mortality
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / therapy
  • Male
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use
  • Transplantation Conditioning* / methods
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors