biostudies-literatureAgarwal RNCI NIH HHSCalifornia Institute for Regenerative Medicine (CIRM)3183-3190https://www.ebi.ac.uk/biostudies/studies/S-EPMC12443608biostudies-literatureUnknown31(9)Current hematopoietic stem cell transplantation (HSCT) conditioning strategies cause widespread tissue damage and systemic toxicities, especially in patients with DNA-repair deficiencies such as Fanconi anemia (FA). We have developed an alternative conditioning approach that incorporates the anti-CD117 antibody, briquilimab, which targets host hematopoietic stem and progenitor cells in place of genotoxic irradiation- and busulfan-based chemotherapy. Here we report a phase 1b clinical trial in patients with FA and bone marrow failure, evaluating safety and efficacy of briquilimab-based conditioning in combination with rabbit anti-thymocyte globulin, cyclophosphamide, fludarabine and rituximab immunosuppression and T cell receptor (TCR)αβ⁺ T cell-depleted and CD19⁺ B ceNature medicineIrradiation- and busulfan-free stem cell transplantation in Fanconi anemia using an anti-CD117 antibody: a phase 1b trial.PMC12443608P30 CA008748CLIN2-14315Pang WWBouge AWlodarski MWAgarwal RWeinberg KChan YYCheng JCVan Hentenryck MKrampf MRWillner HShizuru JANofal RPerriman RJKunte NDin HNKlinger EFBoelens JJSoco CCzechowicz ABertaina AWalck EPorteus MSen SBarbarito GLong-Boyle JRScheck ARoncarolo MGHiroshima LSaini GParkman RIstomina EfalseIrradiation- and busulfan-free stem cell transplantation in Fanconi anemia using an anti-CD117 antibody: a phase 1b trial.Current hematopoietic stem cell transplantation (HSCT) conditioning strategies cause widespread tissue damage and systemic toxicities, especially in patients with DNA-repair deficiencies such as Fanconi anemia (FA). We have developed an alternative conditioning approach that incorporates the anti-CD117 antibody, briquilimab, which targets host hematopoietic stem and progenitor cells in place of genotoxic irradiation- and busulfan-based chemotherapy. Here we report a phase 1b clinical trial in patients with FA and bone marrow failure, evaluating safety and efficacy of briquilimab-based conditioning in combination with rabbit anti-thymocyte globulin, cyclophosphamide, fludarabine and rituximab immunosuppression and T cell receptor (TCR)αβ⁺ T cell-depleted and CD19⁺ B ce2025-01-01T00:00:00Z2025 Sep2026-06-03T11:25:59.888Z2026-04-27T03:10:28.716ZS-EPMC124436084069620710.1038/s41591-025-03817-1