Original Article

Leukemia (2014) 28, 2235–2240; doi:10.1038/leu.2014.145; published online 30 May 2014

Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis

M Stern1, L C de Wreede2, R Brand2, A van Biezen3, P Dreger4, M Mohty5, T M de Witte6, N Kröger7 and T Ruutu8 for the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation

  1. 1Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
  2. 2Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands
  3. 3EBMT Data Office, University Medical Centre Leiden, Leiden, The Netherlands
  4. 4Medizinische Klinik V, Universität Heidelberg, Heidelberg, Germany
  5. 5Department of Hematology, CHU Nantes, Nantes, France
  6. 6Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  7. 7Department of Stem Cell Transplantation, University Medical Center Hamburg Eppendorf, Hamburg, Germany
  8. 8Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Correspondence: Professor M Stern, Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel and University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. E-mail: martin.stern@usb.ch

Received 31 January 2014; Revised 25 March 2014; Accepted 14 April 2014
Accepted article preview online 30 April 2014; Advance online publication 30 May 2014

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Abstract

After allogeneic stem cell transplantation, graft-versus-host disease (GvHD) occurs through recognition of histocompatibility mismatches by donor T lymphocytes. The same mechanism operates in eliminating malignant cells (the graft-versus-tumor or GvT effect). We hypothesized that comparing the correlation between GvHD and relapse might provide a surrogate marker for the susceptibility of diseases to allo-immune effects. We studied 48111 first allogeneic transplants performed between 1998 and 2007. In chronic myeloid leukemia (CML), the relapse risk declined clearly and proportionally to severity of acute and chronic GvHD. Acute lymphoblastic leukemia and BCR-ABL-negative myeloproliferative neoplasias were comparably sensitive to GvHD as CML, whereas myelodysplastic syndromes and lymphoproliferative disorders showed intermediate sensitivity. GvHD was only associated with modest reductions in relapse risk in acute myeloid leukemia (AML) and plasma cell disorders (PCDs). Except for PCD, hazard rates for relapse decreased to almost 0 at 48 months of follow-up in all diseases. These data confirm observations of potent GvT effects associated with GvHD. The strength of the GvHD/GvT correlation differs significantly between hematological malignancies. The parallel drop of relapse rates in different diseases despite differences in GvHD/GvT ratios suggests that GvT effects might operate in the absence of GvHD, particularly in AML.