Adverse impact of a high CD4/CD8 ratio in the allograft may be overcome by methotrexate‐ but not mycophenolate‐ or post‐transplant cyclophosphamide‐based graft versus host disease prophylaxis

Abstract

Introduction: A high CD4/CD8 T cell ratio in hematopoietic stem cell transplant (HSCT) allografts was observed to predict graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) but has not been comparatively examined in settings of various GVHD-prophylaxis regimens.Methods: This retrospective monocentric study included all consecutive HSCT performed with peripheral blood stem cells between January 2000 and June 2021.The impact of the graft CD4/CD8 ratio was analyzed in three cohorts with different GVHD-prophylaxis platforms.Results: In the cyclosporine/mycophenolate-mofetil (CSA/MMF) cohort (n = 294, HLA-matched HSCT), a high (>75th percentile) CD4/CD8 ratio was associated with increased overall mortality (HR: 1.56; p = .01), increased NRM (HR: 1.85; p = .01) and GVHD-associated mortality (HR: 2.13; p = .005). In the post-transplant cyclophosphamide (PTCy)/tacrolimus/MMF cohort (n = 113, haploidentical-related or mismatched-unrelated HSCT), a high CD4/CD8 ratio was associated with increased overall mortality (HR 2.07; p = .04) and aGVHD3-4 (HR: 2.24; p = .02). By contrast, in the CSA/methotrexate (CSA/MTX) cohort (n = 185, HLA-matched HSCT) the CD4/CD8 ratio had no significant impact on any of the investigated endpoints. Conclusion:A high CD4/CD8 ratio in the allograft has an adverse impact on GVHD and survival in CSA/MMF-and PTCy-based HSCT, while MTX-based prophylaxis may largely alleviate this important risk factor.

Graft CD8 T‐cell‐based risk system predicts survival in antithymocyte globulin‐based myeloablative haploidentical peripheral blood stem cell transplantation

“…10 A high CD4/CD8 ratio (> 2.42) was associated with overall mortality (hazard ratio [HR], 2.07; P = 0.04) in HLA-mismatched HSCT with PTCybased GVHD prophylaxis. 9 Graft CD8 + T cells were not an independent factor in the development of GVHD in this study. In line with our findings, several studies have shown that the dose of CD8 + T cells in grafts has no impact on the GVHD.…”

“…7,8 The cellular composition of grafts other than CD34 + cells also affects HSCT clinical outcomes. [9][10][11] However, different cellular populations in the grafts result in distinct clinical outcomes after HSCT. A higher dose of CD3 + T cells in the peripheral blood grafts of haploidentical HSCT (haplo-HSCT) reportedly increases the risk of acute graft-versushost disease (GVHD).…”

“…Nikoloudis et al found that a high CD4/CD8 ratio in peripheral blood stem cells adversely impacted survival in the context of mycophenolate-or posttransplant cyclophosphamide (PTCy)-based GVHD prophylaxis rather than methotrexate-based GVHD prophylaxis. 9 Generally, identification of the optimal graft composition is complicated by the donor type, GVHD prophylaxis and graft sources. Hence, to investigate the impact of the cellular composition of peripheral blood-derived grafts on the clinical outcomes after ATG-based myeloablative haplo-HSCT, we evaluated the clinical data in a training cohort and confirmed it in a validation cohort.…”