Posttransplant Cyclophosphamide and Antithymocyte Globulin versus Posttransplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis for Peripheral Blood Stem Cell Haploidentical Transplants: Comparison of T Cell and NK Effector Reconstitution

J Immunol. 2020 Sep 1;205(5):1441-1448. doi: 10.4049/jimmunol.2000578. Epub 2020 Aug 3.

Abstract

A higher incidence of graft-versus-host disease (GVHD) has been observed after haploidentical hematopoietic stem cell transplantation (h-HSCT) with posttransplant cyclophosphamide (PTCY) using peripheral blood stem cells (PBSC) as a source of graft. Moreover, combining PTCY with antithymocyte globulin (ATG) may help to reduce GVHD incidence. In this study, early immune reconstitution, especially of T and NK cell compartments, was compared after both types of transplant (PTCY versus PTCY + ATG) investigate their influence on patient outcomes. This retrospective study included 58 adults who received a reduced intensity conditioning to PBSC h-HSCT with cyclosporine and mycophenolate mofetyl + PTCY (n = 32) or PTCY + ATG (n = 26) as GVHD prophylaxis. Both groups shared similar characteristics except for the median number of CD3+ T cells infused, significantly higher for PTCY + ATG patients. Blood samples from all patients were collected three times a week from day 0 until day 30 then at day 60 and day 90/100 to evaluate T and NK cells reconstitution by flow cytometry. The results show that PTCY + ATG versus PTCY alone significantly limits the occurrence of acute grade 2-4 GVHD after reduced intensity conditioning PBSC h-HSCT, perhaps because of the combined effect of T and NK cell reconstitution. Indeed, although a slower T cell reconstitution with PTCY + ATG may limit GVHD occurrence, the quicker reconstitution of some NK cell subtypes may help with avoiding relapse. Larger prospective studies are needed to better determine which NK cell subsets may influence the incidence of relapse after h-HSCT and optimize donor selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antilymphocyte Serum / therapeutic use*
  • CD3 Complex / metabolism
  • Cyclophosphamide / therapeutic use*
  • Female
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / metabolism
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / metabolism
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cells / drug effects*
  • Peripheral Blood Stem Cells / metabolism
  • Retrospective Studies
  • Stem Cell Transplantation / adverse effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Transplantation Conditioning / adverse effects
  • Transplantation, Haploidentical / adverse effects
  • Transplantation, Homologous / adverse effects
  • Young Adult

Substances

  • Antilymphocyte Serum
  • CD3 Complex
  • Immunosuppressive Agents
  • Cyclophosphamide