Impact on early outcomes and immune reconstitution of high-dose post-transplant cyclophosphamide vs anti-thymocyte globulin after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation

Abstract

We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) (n = 30) or anti-thymocyte globulin ATG (n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen. The γ/δ T-cells, α/β T-cells (CD8+ and CD4+), NK T-cells, NK cells, B-cells, Tregs and monocytes were analyzed by flow cytometry from a total of 583 samples. In the PTCY group significant delayed platelets recovery, higher CD3+ donor chimerism, higher HHV-6 and lower EBV reactivations were observed. Early survival advantage for CD4+ T-cells, Tregs and α/β T-cells was documented in the PTCY group while it was the case for α/β T-cells, NK cells and monocytes in the ATG group. Higher counts of NK and monocytes were observed at days +30 and/or day+60 in the ATG group. Both results were retained even in the case of mismatched donors. However, higher percentages of CD4+ T-cells, α/β T-cells and Tregs were observed with haplo-identical donors in the PTCY group. Finally, clofarabine was responsible for early survival advantage of NK T-cells in the PTCY group while it abrogated the early survival advantage of γ/δ T-cells in the ATG group. In conclusion, there are marked differences in the immunological effects of ATG vs PTCY as GVHD prophylaxis for RIC PBSC allo-SCT.

Impact of KIR/HLA Incompatibilities on NK Cell Reconstitution and Clinical Outcome after T Cell–Replete Haploidentical Hematopoietic Stem Cell Transplantation with Posttransplant Cyclophosphamide

“…Nineteen of these patients developed acute GvHD at a median time of 34 d (range: 21-119 d) posttransplant. Proliferative NK cells in the graft were particularly targeted by the early administration of PTCy, as shown by the profound depletion in NK cells from day 5 to day 20, confirming previous data from our group (16). Although GvHD, relapse, or inh.…”

“…This biologic study was approved by the Ethics Review Board of the Nantes University Hospital, and all patients and donors included provided informed consent. The outcomes of some patients have been already reported previously (16).…”

A prospective observational study of immune reconstitution following transplantation with post‐transplant reduced‐dose cyclophosphamide from HLA ‐haploidentical donors

“…There are a few reports on immune reconstitution after PT/Cy‐haplo, including those comparing PT/Cy‐haplo to HLA‐haploidentical HCT by anti‐thymocyte globulin (ATG)‐containing conditioning regimen . However, differences in immune reconstitution patterns between PT/Cy‐haplo and after other standard grafts and/or alternative HCTs have not been sufficiently elucidated.…”

Superior immune reconstitution using Treg-expanded donor cells versus PTCy treatment in preclinical HSCT models

“…Although short-term effects of cyclophosphamide on immune function are well defined (17,18), there have been limited studies involving long-term immune reconstitution following PTCy (19,20). Reports have noted that rates of infection and relapse have not been significantly increased in contrast to historical approaches to haploidentical HSCT that were based on ex vivo T cell depletion as well as compared with contemporaneous haploidentical, MRD, and MUD HSCTs (5,(21)(22)(23)(24).…”