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.

Christelle Retière,Alice Garnier,Marie C Béné,Beatrice Clemenceau,Catherine Willem,Xavier Saulquin,Patrice Chevallier,Thierry Guillaume,Katia Gagne,Berthe-Marie Imbert,Pierre Peterlin,Henri Vié,Emmanuel Scotet,Laetitia Gautreau-Rolland

doi:10.18632/oncotarget.24328

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.

Highlights

RESULTSAfter the revolution that has constituted almost twenty years ago the introduction of reduced intensity conditioning (RIC) regimens, allowing to perform allogeneic stem cell transplantation in older patients or patients with co-morbidities, [1,2,3] a new step has been taken this last decade by reconsideration of haplo-identical family donors
Between days 0–90/100, the rate of HHV-6 reactivations was significantly increased in the post-transplant cyclophosphamide (PTCY) group (53% vs 7%, p = 0.0017) while EBV reactivations were significantly associated with the anti-thymocyte globulin (ATG) group (73% vs 20%, p = 0.0003)
Considering absolute numbers, ATG patients had higher median counts of NK and monocytes at day +30, of α/β and γ/δ T-cells and NK T-cells at day+60 and of NK T-cells at day+90/100 (Figure 4B). This prospective study aimed to clarify the influence of PTCY on early outcome and immune reconstitution after peripheral blood stem cell (PBSC) reduced-intensity conditioning (RIC) allo-SCT, either using matched or haploidentical donors

Summary

RESULTS

After the revolution that has constituted almost twenty years ago the introduction of reduced intensity conditioning (RIC) regimens, allowing to perform allogeneic stem cell transplantation (allo-SCT) in older patients or patients with co-morbidities, [1,2,3] a new step has been taken this last decade by reconsideration of haplo-identical family donors. When considering only matched donors (PTCY n = 10, ATG n = 15), between days 0–30, percentages of α/β T-cells, Tregs and CD4+ T-cells were significantly higher in the PTCY group while it was the case for NK cells, B-cells and monocytes in the ATG group (Figure 3A). When considering only PTCY patients with haplo-identical donors, comparison of both groups (ATG vs PTCY) showed, between days 0–30, significantly higher percentages of α/β T-cells, Tregs and CD4+ T-cells for PTCY www.impactjournals.com/oncotarget patients and higher percentages of NK cells, B-cells and monocytes for ATG patients (Figure 3A). When considering only patients receiving clofarabinebased regimens (PTCY n = 15, ATG n = 10), between days 0–30, the percentages of α/β T-cells, Tregs, CD4+ T-cells and NK T-cells were significantly higher in the PTCY group while it was the case for B and NK cells, and monocytes in the ATG group (Figure 4A). Considering absolute numbers, ATG patients had higher median counts of NK and monocytes at day +30, of α/β and γ/δ T-cells and NK T-cells at day+60 and of NK T-cells at day+90/100 (Figure 4B)

DISCUSSION

Findings

Study design and data collection