Donor-derived CD4+/CCR7+ T-cell impact on acute GVHD incidence following haplo-HCT after reduced intensity conditioning and posttransplant cyclophosphamide

Bone Marrow Transplant. 2019 Oct;54(10):1686-1693. doi: 10.1038/s41409-019-0511-7. Epub 2019 Mar 19.

Abstract

In previous studies, we and others observed in patients undergoing HLA-matched hematopoietic cell transplantation that high proportion of donor-derived CD4+/CCR7+ T cells were associated with an increased risk of acute GVHD without any interference in relapse incidence. We investigated the impact of donor-derived CD4+/CCR7+ T cells on patient outcome in haploidentical settings where posttransplant cyclophosphamide is used. We analyzed T-cell subsets in grafts of 29 adult patients who underwent first haploidentical transplant following reduced intensity conditioning. The median CD4+/CCR7+ subset proportion was 69.2% among donor CD4+ T cells. With a median follow-up of 28.1 months (range: 11.0-44.3), 16 patients (55%) developed acute GVHD; this includes 5 patients with grade 3 acute GVHD. Fifty-four percent of patients who received > 69.2% of CD4+/CCR7+ T cells and 12% of patients who received < 69.2% CD4+/CCR7+ T cells developed acute GVHD (p = 0.028). In multivariate analysis, a high proportion of CD4+/CCR7+ T cells was the only factor that impacted acute GVHD (HR = 4.925, 95% CI [1.020-23.775], p = 0,047) with no impact on overall survival. Our results confirm the impact of a high proportion of CD4+/CCR7+ T cells on acute GVHD incidence in patients undergoing haploidentical transplant despite the use of posttransplant cyclophosphamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use*
  • Female
  • Graft vs Host Disease / genetics*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Receptors, CCR7 / metabolism*
  • Retrospective Studies
  • Transplantation Conditioning / methods*
  • Transplantation, Haploidentical / methods*
  • Young Adult

Substances

  • CCR7 protein, human
  • Receptors, CCR7
  • Cyclophosphamide