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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schulz, E; Curtis, LM; Holtzman, NG; Sponaugle, J; Wloka, K; Ostojic, A; Mina, A; El, Jurdi, N; Pirsl, F; Carpenter, A; Golagha, M; Sirajuddin, A; Heller, T; Shaffer, BC; Hakim, FT; Rubin, JS; Gress, RE; Pavletic, SZ.
Phase 1/2 Study of High-Dose Palifermin for GVHD Prophylaxis in Patients Undergoing HLA-Matched Unrelated Donor HCT.
Blood. 2025;
Doi: 10.1182/blood.2024028303
PubMed
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- Abstract:
- Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). Palifermin, a recombinant N-truncated keratinocyte growth factor (KGF), protects epithelial tissues, including the thymus and gut. While high-dose KGF prevents GVHD in preclinical models, lower doses of palifermin were ineffective in humans. We conducted a phase 1/2 trial evaluating high-dose palifermin for preventing severe chronic GVHD (GVHD) in matched unrelated donor T-cell replete peripheral-blood HCT following reduced-intensity conditioning (RIC). Using a 3+3 design, we determined the recommended phase 2 dose (RP2D), followed by an expansion phase. Palifermin (180-720 μg/kg) was given on day -7 before HCT. All 31 patients received fludarabine/cyclophosphamide RIC with tacrolimus, methotrexate, and sirolimus for GVHD prophylaxis. Palifermin was well tolerated, with self-limiting rash and pancreatic enzyme elevations as notable grade 3/4 adverse events. The RP2D was 720 μg/kg. Remarkably, no patients at this dose developed grade II-IV acute GVHD (0/19), though severe chronic GVHD rates (primary endpoint) remained unchanged compared to historical controls. Post-transplant lymphocyte phenotyping suggests palifermin modulates Treg and naïve CD4+ T-cell numbers. These findings indicate high-dose palifermin with RIC is safe and may prevent acute GVHD, though it did not impact chronic GVHD rates in this study. NCT02356159.