HLA-DP mismatch and CMV reactivation increase risk of aGVHD independently in recipients of allogeneic stem cell transplant

Curr Res Transl Med. 2019 May;67(2):51-55. doi: 10.1016/j.retram.2019.01.001. Epub 2019 Jan 23.

Abstract

HLA-DP mismatched allogeneic hematopoietic stem cell transplantation (allo-HCT) is associated with increased risk of aGVHD and decreased risk of relapse with no effects on overall survival (OS). It has been proposed that CMV-reactivation induces expression of HLA-DP molecules on GVHD target tissues by releasing inflammatory cytokines. We hypothesized that the increased GVHD incidence in HLA-DP mismatched allo-SCTs correlates with recipient CMV serostatus or CMV reactivation. In addition, CMV reactivation is associated with increased risk of GVHD with an unknown mechanism. Here, we analyzed the association between HLA-DPB1 and CMV reactivation on cumulative incidence of aGVHD and relapse as well as OS in 613 patients with AML and MDS who underwent matched related or unrelated allo-HCT at MD Anderson Cancer Center from 2005 to 2011. In multivariable analysis, HLA-DPB1 mismatching was associated with increased risk of aGVHD (hazard ratio (HR): 1.53, P < 0.001) independent of CMV serostatus and CMV reactivation. Additionally, HLA-DPB1 mismatching was associated with decreased risk of relapse and no effect on OS. CMV reactivation increased risks of aGVHD (HR: 5.82, P < 0.001) independent of HLA-DP mismatching with no effect on relapse or OS. In conclusion, our data suggests that HLA-DPB1 mismatching and CMV reactivation increase risk of aGVHD independently.

Keywords: Allogeneic hematopoietic stem cell transplantation; CMV; HLA-DP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / complications*
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Female
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / virology
  • HLA-DP Antigens / genetics
  • HLA-DP Antigens / immunology*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / statistics & numerical data
  • Histocompatibility Testing / adverse effects*
  • Humans
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / complications
  • Myelodysplastic Syndromes / epidemiology
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / therapy
  • Retrospective Studies
  • Risk Factors
  • Transplant Recipients / statistics & numerical data
  • Transplantation Immunology
  • Transplantation, Homologous / adverse effects
  • Virus Activation / physiology*
  • Young Adult

Substances

  • HLA-DP Antigens