HLA-DQB1 mismatch increase risk of severe bleeding independently in recipients of allogeneic stem cell transplant

Ann Hematol. 2021 Sep;100(9):2351-2361. doi: 10.1007/s00277-021-04520-0. Epub 2021 Apr 12.

Abstract

Severe bleeding is a major cause of death in acute leukemia (AL) patients with graft-versus-host disease (GVHD) after allogene hematopoietic stem-cell transplantation (allo-HSCT). However, the prognostic value and prediction of HSCT-associated severe bleeding in GVHD patients have not been reported in cohort studies. We did a retrospective analysis of 200 AL patients with GVHD after allo-HSCT from Feb 1, 2014, to Dec 1, 2015. Multivariate analysis showed that the severe bleeding class was associated with the risk of death (HR 2.26, 95% CI 1.31-3.92, p<0.001***). In order to predict severe bleeding and figure out the solution to bleeding events, we established a multiple logistic regression model. HLA-DQB1 unmatching, megakaryocyte reconsititution failure, and III or IV GVHD were the independent risk factors for severe bleeding. Among all the variations above, OR of HLA-DQB1 was the highest (OR: 16.02, 95% CI: 11.54-48.68). Adding HLA-DQB1 to other factors improved the reclassification for predicting severe bleeding (NRI=0.195, z=2.634, p=0.008**; IDI=0.289, z=3.249, p<0.001***). Lasso regression was used to select variants. A nomogram of the logistic model was generated and displayed. Calibration curve demonstrated excellent accuracy in estimating severe bleeding (C index of 0.935). HLA-DQB1 showed excellent efficacy of predicting severe bleeding in HSCT patients.

Keywords: Acute leukemia; Graft-versus-host disease; HLA-DQB1; Hematopoietic stem-cell transplantation; Severe bleeding.

MeSH terms

  • Adult
  • Female
  • Graft vs Host Disease / etiology*
  • HLA-DQ beta-Chains / analysis*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hemorrhage / etiology*
  • Humans
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Retrospective Studies
  • Risk Factors
  • Transplantation Conditioning
  • Transplantation, Homologous / adverse effects

Substances

  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen