Delayed CD4+ T-Cell but Faster B-Cell Immune Reconstitution after Ptcy-Based Compared to Conventional Gvhd Prophylaxis after Allogeneic Transplantation

Background Post-transplant cyclophosphamide (PTCY) is being increasingly used for graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT) across various donor types. However, immune reconstitution after PTCY-based vs. conventional GVHD prophylaxis has not been well studied. Methods We evaluated the pace of immune reconstitution (CD4+ T-cell, CD8+ T-cell, NK-cell and B-cell) at 3 months, 6 months and 1 year post-HCT in 583 adult patients receiving myeloablative (n=223) or reduced intensity conditioning (n=360) HCT (2012-2018). Haploidentical (Haplo; n=75) and 8/8 HLA-matched unrelated (MUD, n=508) donor types were included. GVHD prophylaxis was PTCY-based in 75 Haplo and 38 MUD (MUD-PTCY) HCT, while tacrolimus/methotrexate (TAC/MTX) was used in 89 and TAC/Sirolimus (TAC/SIR) in 381 MUD HCT. Clinical outcomes including viral infections, non-relapse mortality (NRM) and overall survival (OS) were compared across all four treatment groups. Results The recovery of absolute total CD4+ T-cell count after Haplo-PTCY and MUD-PTCY was significantly lower compared to MUD TAC/MTX or MUD TAC/SIR throughout 1 year of HCT (Figure). In contrast, CD19+ B-cell recovery at 6 months and thereafter was more rapid after Haplo-PTCY and MUD-PTCY HCT in comparison to MUD TAC/MTX and MUD TAC/SIR. In subgroup analysis compared to MUD TAC/MTX HCT, total CD8+ T-cell or NK-cell recovery was not significantly different after Haplo-PTCY or MUD-PTCY HCT. However, patients receiving MUD TAC/SIR vs. MUD TAC/MTX had significantly slower reconstitution of total CD8+ T-cells up to 6 months and CD19+ B-cells at 1 year of HCT, but no significant differences in CD4+ T-cell or NK-cell recovery. The distribution of recipient CMV serostatus was similar in all four groups: 72% in Haplo-PTCY, 62 % in MUD-PTCY HCT, 68% in MUD TAC/MTX and 63% in MUD TAC/SIR (p=0.11). Cumulative incidence of CMV reactivation/infection at 1-year of HCT was higher in patients receiving Haplo-PTCY (39.6%) or MUD TAC-MTX (37.7%) compared to those receiving MUD-PTCY (27.0%) or MUD TAC/SIR (22.8%; p Conclusion Our data demonstrate that the pattern of immune reconstitution after HCT is different after PTCY-based vs. conventional GVHD prophylaxis with delayed total CD4+ T-cell but more rapid B-cell recovery after PTCY-based GVHD prophylaxis. The rates of CMV and EBV viral infections were different across the donor types. However, these differences had no significant influence on NRM or survival after HCT.