Impact of anti-thymocyte globulin on results of allogeneic peripheral blood stem cell transplantation for patients with Philadelphia-positive acute lymphoblastic leukaemia: An analysis by the Acute Leukemia Working Party of the EBMT

Eur J Cancer. 2019 Jan:106:212-219. doi: 10.1016/j.ejca.2018.11.003. Epub 2018 Dec 6.

Abstract

Background: Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL).

Methods: In the analysis, 1170 adult patients undergoing alloPBSCT from human leucocyte antigen-matched sibling or unrelated donors in the first complete remission between 2007 and 2016 were included. ATG was used in 429/575 (75%) and 121/595 (20%) patients transplanted from unrelated or sibling donors, respectively.

Results: The incidence of chronic GVHD was 35% for patients treated with ATG compared with 52% in those not receiving ATG (p < 0.001), while the rate of extensive chronic GVHD was 16% and 36%, respectively (p < 0.001). The probability of survival free from GVHD and relapse (GRFS) was 42% and 32%, respectively (p = 0.002). In a multivariate model, the use of ATG was associated with reduced risk of overall chronic GVHD (hazard ratio [HR] = 0.52, p < 0.001) and extensive chronic GVHD (HR = 0.46, p < 0.001). It was also associated with better GRFS (HR = 0.77, p = 0.007), despite increased risk of relapse (HR = 1.41, p = 0.02). No significant effect was found with regard to the risk of non-relapse mortality and overall mortality.

Conclusions: The use of ATG for patients with Ph+ ALL undergoing alloPBSCT is associated with reduced risk of chronic GVHD without impact on survival and therefore, could be considered. However, increased risk of relapse suggests the need for strict monitoring of minimal residual diseases and appropriate interventions after transplantation.

Keywords: Acute lymphoblastic leukaemia; Allogeneic haematopoietic cell transplantation; Anti-thymocyte globulin; Graft-versus-host disease; Leukaemia-free survival; Philadelphia positive.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antilymphocyte Serum / adverse effects
  • Antilymphocyte Serum / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Europe
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / surgery*
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation* / adverse effects
  • Peripheral Blood Stem Cell Transplantation* / mortality
  • Philadelphia Chromosome*
  • Progression-Free Survival
  • Protective Factors
  • Recurrence
  • Registries
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Biomarkers, Tumor
  • Immunosuppressive Agents