Modifying Post-Transplant Cyclophosphamide Platform to Improve Safety in HLA-Matched Allogeneic HCT: A Reduced Dose Plus Adjunctive Strategies
Pinto FR, Salas MQ, Suárez-Lledó M, Pedraza A, Charry P, de Moner B, Martínez-Sanchez J, Carcelero E, Guardia L, Cascos E, Cid J, Lozano M, Esteve J, Carreras E, Díaz-Ricart M, Rosiñol L, Fernández-Avilés F, Rovira M, Martínez C.
TRANSPL CELL THER
Post-transplant cyclophosphamide (PTCY, 50 mg/kg/day for 2 days) is effective for GVHD prophylaxis after HLA-matched allogeneic hematopoietic cell transplantation (allo-HCT) but is associated with early toxicities. In November 2021, we implemented a modified platform using reduced-dose PTCY (40 mg/kg; PTCY40) with tacrolimus, plus G-CSF from day +7 and letermovir for CMV-positive patients. Outcomes of 56 patients receiving PTCY40 were compared to 59 historical controls treated with PTCY50. Median follow-up was 15 months. PTCY40 was associated with faster neutrophil and platelet recovery (median 15 vs. 19 and 15 vs. 21 days, respectively), improved CD4⁺ reconstitution, and fewer bloodstream infections by day +30 (19.6% vs. 49.2%, p=0.001). Early cardiac events and ICU admissions were numerically lower in the PTCY40 group (day +100: 5.4% vs. 10.2%, p=0.358; day +180 ICU: 5.4% vs. 10.2%, p=0.411). The cumulative incidence of grade II-IV acute GVHD was comparable (21.4% vs. 18.6%, p=0.641), while moderate/severe chronic GVHD was higher but not significant (1-year: 9.5% vs. 1.9%, p=0.105). Non-relapse mortality was significantly lower with PTCY40 (0% vs. 8.6%, p=0.032), with similar overall survival (78.2% vs. 81.1%, p=0.941) and relapse incidence (25.1% vs. 24.1%, p=0.772). These findings support the safety of this modified GVHD prophylaxis approach.
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