Superior Chronic GVHD-Free Survival with Post-Transplant Cyclophosphamide Relative to Tacrolimus/Methotrexate in Myeloablative HLA-Matched Allogeneic Hematopoietic Cell Transplantation.

Abstract

Graft-versus-host disease (GVHD) has been a significant barrier to successful myeloablative (MAC) allogeneic hematopoietic cell transplantation (HCT). Traditional GVHD prophylaxis with calcineurin inhibitor and methotrexate (TAC/MTX) is associated with substantial GVHD. Controversy exists over whether post-transplant cyclophosphamide (PTCy) should replace TAC/MTX as standard of care for MAC HCT using HLA-matched donors.We conducted a retrospective cohort study of 237 adult patients with acute myeloid leukemia (AML, n=164) or acute lymphoblastic leukemia (ALL, n=73) who underwent MAC followed by HLA-matched HCT at our center between 2018 and 2025. Patients were evaluated based on GVHD prophylaxis: PTCy/TAC/mycophenolate mofetil (MMF) or TAC/MTX. Kaplan-Meier and competing-risks methods were applied, with outcomes further stratified by pre-HCT measurable residual disease (MRD).Of 237 patients, 46 received PTCy/TAC/MMF and 191 received TAC/MTX. Baseline characteristics, remission status, and pre-HCT MRD were comparable between groups. The 1-year chronic GVHD-free survival was significantly superior with PTCy relative to TAC/MTX (86.3% vs 61.7%, p=0.006). This was due to significantly lower moderate to severe chronic GVHD at 1 year (7% vs 21%, p=0.02) and significantly lower NRM at 1 year (2.2% vs 10.5%, p = 0.04) with PTCy. Overall survival (OS) and progression-free survival (PFS) were similar between PTCy and TAC/MTX (OS: 93.3% vs. 82.1%, p = 0.2; PFS: 70.2% vs. 74.8%, p = 0.6, respectively); 1-year GVHD-free, relapse-free survival (GRFS) trended higher with PTCy versus TAC/MTX (63.5% vs 50.2%, p = 0.09). We then evaluated outcomes of PTCy vs TAC/MTX stratified by pre-HCT MRD [PTCy: MRD+ 35% (n=16), MRD- 63% (n=29), unknown 2% (n=1); TAC/MTX: MRD+ 34% (n=65), MRD- 50% (n=96), unknown 16% (n=30)]. Similar trends in superior GVHD rates, NRM, and GRFS were observed following PTCy in both MRD+ and MRD- cohorts. The cumulative incidence of relapse at 1-year did not differ between PTCy and TAC/MTX among MRD- patients (14.1% vs 9%, p = 0.41); however, we observed a strikingly high incidence of relapse among MRD+ patients treated with PTCy relative to TAC/MTX (51.9% vs 23.3%, p = 0.06).In this single-center analysis, PTCy-based GVHD prophylaxis demonstrated superior chronic GVHD-free survival, significantly reduced NRM, and trends toward higher GRFS compared with TAC/MTX in MAC HLA-matched HCT for acute leukemia. However, a signal of increased relapse, particularly among patients with detectable MRD before HCT, warrants further investigation. Integrating enhanced anti-leukemic strategies with PTCy platforms may optimize long-term outcomes.

View details for DOI 10.1016/j.jtct.2026.03.029

View details for PubMedID 41895692