The importance of graft cell composition in outcome after allogeneic stem cell transplantation in patients with malignant disease

Clin Transplant. 2019 Jun;33(6):e13537. doi: 10.1111/ctr.13537. Epub 2019 May 7.

Abstract

Background: Graft-versus-host disease (GVHD) and relapse remain majobstacles ftreatment success in allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, we evaluated the immune cell profile of the graft to outcome after HSCT.

Study design and method: Flow cytometry data of graft cell subsets [CD34+ , CD3+ , CD19+ , CD4+ , CD8+ , CD3-CD56+ CD16+ , CD4+ CD127low CD25high ] from G-CSF primed peripheral blood stem cell (PBSC) donors was collected retrospectively from 299 patients with hematological malignancies undergoing HSCT between 2006 and 2013. The association to overall survival, transplant-related mortality (TRM), GVHD and probability of relapse was analyzed. Patients outcome from HLA-identical sibling (Sib) (n = 97) and unrelated donors (URD) (n = 202) were analyzed separately as all URD patients received anti-thymocyte globulin (ATG).

Results: Five-year overall survival was similar in the two cohorts (68% (Sib) vs 65% (URD)). The relapse incidence was significantly lower in the Sib cohort (24% vs 35%, P = 0.04). Multivariate analysis in the URD group revealed an association between a higher CD8+ dose and less relapse (HR, 0.94; 95%CI, 0.90-0.98; P = 0.006) as well as an association between higher CD34+ dose and both higher TRM (HR, 1.09; 95%CI, 1.02-1.20; P = 0.02) and relapse (HR, 1.09; 95%CI, 1.01-1.17; P = 0.025). The Sib analysis showed an association between a higher graft CD19+ dose and more severe acute GVHD (HR, 1,09; 95%CI, 1.03-1.15; P = 0.003) and TRM (HR, 1.09; 95%CI, 1.01-1.17; P = 0.036). In addition, a higher CD4+ graft content was associated to an increased risk for chronic GVHD (HR, 1.02; 95%CI 1.00-1.04; P = 0.06).

Conclusion: These data indicate an importance of PBSC dongraft composition in patients with a hematological malignancy.

Keywords: donor cell composition; flow cytometry; graft-vs-host disease; hematopoietic stem cell transplantation; peripheral blood stem cells; relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / analysis*
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Graft Survival / immunology*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / metabolism
  • Graft vs Host Disease / mortality*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / metabolism
  • Hematologic Neoplasms / mortality*
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / mortality*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / etiology
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • T-Lymphocyte Subsets / immunology*
  • Tissue Donors / supply & distribution*
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antigens, CD