Conditioning with an anti-CD117 antibody and lymphodepletion prior to HSCT in Fanconi anemia
Agarwal R, Bertaina A, Soco C, et al. Irradiation- and Busulfan-Free Stem Cell Transplantation in Fanconi Anemia Using an Anti-CD117 Antibody: A Phase 1B Trial. Nature Medicine. 2025; (doi: 10.1038/s41591-025-03817-1).
Conventional conditioning methods ahead of allogeneic hematopoietic stem cell transplantation (allo-HSCT) can lead to tissue damage and systemic toxicities in patients with Fanconi anemia (FA), but an experimental method promises a safer alternative to total body irradiation (TBI)- and busulfan-based chemotherapy. The technique pairs the anti-CD117 antibody briquilimab with a lymphodeletion regimen, a protocol that was evaluated in a Phase 1b study of three participants with FA and bone marrow failure (BMF). Following conditioning, each underwent transplantation with TCRαß+ T cell-depleted and CD19+ B cell-depleted hematopoietic stem and progenitor cells — an approach that promotes donor hematopoietic and immune reconstitution, curbs graft-versus-host disease (GVHD), and widens the pool of potential donors. No participants experienced treatment-emergent adverse events or acute GVHD, and toxicities were minimal overall. Engraftment was achieved in a median 11 days without TBI or busulfan, and hematopoiesis was fully restored. Up to 2 years post-transplantation, donor chimerism was 99%-100%. The results suggest the novel conditioning protocol reduces toxicity in haploidentical allo-HSCT among immunocompetent patients. The authors believe it also could benefit patients with other BMF disorders or advanced hematopoietic diseases.