Pre-transplant donor CD4 - invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease

Leukemia. 2017 Apr;31(4):903-912. doi: 10.1038/leu.2016.281. Epub 2016 Oct 14.

Abstract

Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34+, NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4- iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4- iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4- iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4- iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / immunology*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Male
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Preoperative Period
  • Prognosis
  • Severity of Illness Index
  • Tissue Donors*
  • Transplantation, Homologous