Modifying Post-Transplant Cyclophosphamide Platform to Improve Safety in HLA-Matched Allogeneic HCT: A Reduced Dose
Filipe R Pinto1, María Queralt Salas2, María Suárez-Lledó2
1Hematopoietic Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases (ICAMS), Hospital Clínic de Barcelona, Barcelona, Spain.
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 versus 19 and 15 versus 21 days, respectively), improved CD4⁺ reconstitution, and fewer bloodstream infections by day +30 (19.6% versus 49.2%, P = .001). Early cardiac events and ICU admissions were numerically lower in the PTCY40 group (day +100: 5.4% versus 10.2%, P = .358; day +180 ICU: 5.4% versus 10.2%, P = .411). The cumulative incidence of grade II-IV acute GVHD was comparable (21.4% versus 18.6%, P = .641), while moderate/severe chronic GVHD was higher but not significant (1-year: 9.5% versus 1.9%, P = .105). Non-relapse mortality was significantly lower with PTCY40 (0% versus 8.6%, P = .032), with similar overall survival (78.2% versus 81.1%, P = .941) and relapse incidence (25.1% versus 24.1%, P = .772). These findings support the safety of this modified GVHD prophylaxis approach.
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 versus 19 and 15 versus 21 days, respectively), improved CD4⁺ reconstitution, and fewer bloodstream infections by day +30 (19.6% versus 49.2%, P = .001). Early cardiac events and ICU admissions were numerically lower in the PTCY40 group (day +100: 5.4% versus 10.2%, P = .358; day +180 ICU: 5.4% versus 10.2%, P = .411). The cumulative incidence of grade II-IV acute GVHD was comparable (21.4% versus 18.6%, P = .641), while moderate/severe chronic GVHD was higher but not significant (1-year: 9.5% versus 1.9%, P = .105). Non-relapse mortality was significantly lower with PTCY40 (0% versus 8.6%, P = .032), with similar overall survival (78.2% versus 81.1%, P = .941) and relapse incidence (25.1% versus 24.1%, P = .772). These findings support the safety of this modified GVHD prophylaxis approach.
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