Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

Leukemia. 2012 Dec;26(12):2462-8. doi: 10.1038/leu.2012.135. Epub 2012 May 22.

Abstract

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P<0.0.001) owing to high risk of nonrelapse mortality (NRM; HR=5.2, P<0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR=0.72; P=0.07) translating into a better OS (HR=1.8; P<0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR=0.65; P=0.02) but also with higher NRM (HR=3.5; P<0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P<0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR=0.65; P=0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / therapy
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Young Adult