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Delayed Engraftment after Post-Transplant Cyclophosphamide (PTCY) Gvhd Prophylaxis in Patients with Myelofibrosis (MF)

Year: 2025

Type: article

Abstract: Background PTCY-based regimens are now standard-of-care for graft-versus-host disease (GVHD) prophylaxis for reduced intensity unrelated donor transplantation (HCT). MF patients may have splenomegaly and marrow microenviromental defects that can affect engraftment . To determine whether PTCY had a detrimental effect on engraftment , we compared the clinical outcomes of patients receiving PTCY and non-PTCY regimens. Methods Patients receiving a first HCT for MF from 2016 - 2023 were included. The primary endpoint was neutrophil engraftment and secondary endpoints were platelet engraftment, graft failure (GF), acute/chronic GVHD, relapse, non-relapse mortality (NRM), progression-free survival (PFS) and overall survival (OS). Results 140 patients met the eligibility criteria: 49 received a PTCY-based and 91 a calcineurin inhibitor-based regimen (CNI). For the entire cohort, mutations were observed in JAK2 (64.3%), CALR (17.9%), and MPL (10.7%). Median age was 64 in both groups (p=0.9) and baseline characteristics were balanced except that the PTCY group received more reduced intensity conditioning (91.7 vs 68.1%) and more haploidentical transplants (22.9 vs 0%). Moreover, fewer patients in the PTCY group were transplanted for primary MF (50 vs 89%). Median follow-up for survivors was 47.1 months (range 9.2, 100). 5 patients failed to achieve an absolute neutrophil count ≥ 0.5 × 10 9 cells/µL for 3 consecutive days (2.04% in PTCY vs 4.4% in CNI, p=0.66) and 25 patients failed to achieve a platelet count of ≥20,000 × 10 9 cells/µL (22.5% in PTCY vs 15.4% in CNI, p=0.36). Among engrafted individuals, the median time to neutrophil engraftment was 18 days for PTCY and 15 days for CNI, p<0.0001. ( Figure A ) Median time to platelet recovery was 33.5 and 26 days for PTCY and CNI, respectively, p=0.0005. ( Figure B ). The GF rate (primary/secondary GF or graft exhaustion) was higher but not significantly higher (27% for PTCY and 16% for CNI, p=0.15) ( Figure C ) as was the use of boost/2 nd transplant (20.4% vs 10%, p=0.12). The acute GVHD rate was similar but the chronic GVHD rate was substantially lower after PTCY compared with CNI; all chronic GVHD at 2-years: 12% for PTCY and 49% for CNI (p<0.0001) and moderate/severe chronic GVHD : 8.2 vs 39% (p=0.0003). All other outcomes were similar (3-yr estimates: 75 vs 74% for OS, p=0.76; 60 vs 71% for PFS, p=0.56; 12 vs 17% for NRM, p=0.68; 27 vs 12% for relapse, p=0.22). In multivariable analysis adjusting for baseline characteristics, PTCY was significantly associated with delayed neutrophil engraftment (subdistribution HR (sHR) 0.46, p<0.0001) and less chronic GVHD (sHR 0.23, p=0.005), but did not affect OS, PFS, NRM or relapse. Conclusion PTCY in patients with MF is associated with delayed neutrophil and platelet engraftment without compromising relapse, NRM, or survival. Further study into the reasons and factors associated with poor engraftment are warranted.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.233