Key Points
PTCY + ATG versus PTCY limits the occurrence of grade 2–4 acute GVHD after RIC PBSC h-HSCT.
Quicker reconstitution of some NK cell subtypes may help to avoid relapse.
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.
Footnotes
↵1 P.C. and C.R. have equally contributed to this work.
This work was supported by the Etablissement Français du Sang/Centre Pays de la Loire and by grants from the International Research Group on Unrelated Hematopoietic Stem Cell Transplantation, la Ligue contre le Cancer (Comité de Loire-Atlantique, Comité de la Vienne, Comité de la Vendée, Comité du Morbihan et le Comité des Deux Sèvres), le Département Hospitalo-Universitaire Oncogreffe, Leucémie Espoir Atlantique Famille, and Agence de Biomédecine. D.R.M. is a Ph.D. student supported by Industrial Agreement for Training through Research Grant 2017/0850.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- ALL
- acute lymphoblastic leukemia
- AML
- acute myeloid leukemia
- ATG
- antithymocyte globulin
- BM
- bone marrow
- D
- donor
- DFS
- disease-free survival
- GRFS
- GVHD-free/relapse-free survival
- GVHD
- graft-versus-host disease
- GvL
- graft-versus-leukemia
- h-HSCT
- haploidentical hematopoietic stem cell transplantation
- HSCT
- hematopoietic stem cell transplantation
- inc.
- incompatibility
- KIR
- killer Ig-like receptor
- NRM
- nonrelapse mortality
- OS
- overall survival
- PBSC
- peripheral blood stem cell
- PTCY
- posttransplant cyclophosphamide
- R
- recipient
- RIC
- reduced intensity conditioning.
- Received May 19, 2020.
- Accepted July 4, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.