Post-transplant Cyclophosphamide as GVHD Prophylaxis in Patients Receiving Mismatched Unrelated HCT: The PHYLOS Trial

Among 77 enrolled patients, the cumulative incidence of grades 2 to 4 aGVHD at day 100 post-transplantation was 18.2% (95% CI, 10.6–27.6%).

Researchers from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) conducted the PHYLOS trial and found that post-transplant cyclophosphamide (PTCy)-based prophylaxis significantly reduces the incidence and severity of acute graft-versus-host disease (aGVHD) in patients undergoing hematopoietic stem cell transplantation (HSCT) from mismatched unrelated donors (MMUD). Among 77 enrolled patients, the cumulative incidence of grades 2-4 aGVHD at day 100 post-transplantation was low at 18.2% (95% CI, 10.6–27.6%), with severe aGVHD (grades 3/4) occurring in only 6.5% (95% CI, 3.1–15.1%) of cases.

Allogeneic HSCT from mismatched unrelated donors traditionally poses significant clinical challenges due to heightened risks of severe GVHD, nonrelapse mortality (NRM), and poor survival outcomes compared to matched donor transplantation. Current GVHD prevention strategies for MMUD transplants, such as in vivo T-cell depletion methods, have shown variable efficacy. Given the promising results observed with PTCy in haploidentical transplantation settings, the researchers aimed to evaluate its potential to reduce GVHD and improve outcomes in a more challenging cohort. The study involved patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing myeloablative conditioning consisting of busulfan and fludarabine, followed by administration of PTCy combined with a calcineurin inhibitor and mycophenolate mofetil.

The trial demonstrated favorable clinical outcomes, with a 1-year cumulative incidence of chronic GVHD at 13.4% (95% CI, 6.9-22.1%) and low nonrelapse mortality at 9.1% (95% CI, 4.0–16.9%). The relapse rate within one year post-transplantation was 23.8% (95% CI, 14.9 – 33.9%). Furthermore, one-year overall survival was high at 78.6% (95% CI, 67.4–86.3%), and graft relapse-free survival was 55.3% (95% CI, 43.4–65.7%). These outcomes suggest that PTCy-based prophylaxis can effectively mitigate the negative impact of HLA mismatch in MMUD HSCT, potentially redefining standards of GVHD prophylaxis and improving survival rates in this high-risk transplantation scenario.

Reference

Raiola AM, Bruno B, Risitano AM, et al. Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial. Blood Advances. 2025;9(8):1966-1974.

doi.10.1182/bloodadvances.2024015173