Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT

Eur J Cancer. 2018 Jun:96:73-81. doi: 10.1016/j.ejca.2018.03.018. Epub 2018 Apr 18.

Abstract

Background: Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs).

Methods: We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014.

Results: In univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)-based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01).

Conclusion: In the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL.

Keywords: AlloHSCT; AutoHSCT; GvHD; Minimal residual disease; Ph-positive ALL; Tyrosine kinase inhibitors.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Clinical Decision-Making
  • Europe
  • Female
  • Genetic Predisposition to Disease
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Israel
  • Male
  • Middle Aged
  • Phenotype
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / surgery*
  • Protein Kinase Inhibitors / therapeutic use
  • Registries
  • Remission Induction
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Transplantation Conditioning / methods
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Protein Kinase Inhibitors