A Stanford Medicine team reports that a single dose of the anti‑CD117 antibody briquilimab allowed three children with Fanconi anemia to undergo stem cell transplants without radiation or busulfan, achieving near‑complete donor cell engraftment in a phase 1b study published in Nature Medicine.
What the study found
A peer‑reviewed Nature Medicine paper describes a phase 1b trial at Stanford Medicine in which three children with Fanconi anemia received a single dose of the anti‑CD117 (c‑KIT) antibody briquilimab and then underwent haploidentical hematopoietic stem cell transplantation (HSCT) without total‑body irradiation or busulfan. All three achieved robust, long‑term donor engraftment. (dx.doi.org)
How the regimen worked
Patients were given briquilimab (0.6 mg/kg) on day −12, followed by a reduced‑intensity immunosuppression program (rabbit anti‑thymocyte globulin, low‑dose cyclophosphamide, fludarabine and rituximab). Donor grafts came from half‑matched family members and were processed to deplete TCRαβ+ T cells and CD19+ B cells, a technique developed by Stanford’s Alice Bertaina and colleagues to reduce graft‑versus‑host disease and enable haploidentical transplants. (nature.com)
Outcomes
Neutrophil engraftment occurred in 11–13 days and platelet engraftment in 11–14 days. Multilineage donor chimerism measured 92–100% at 30 days and reached 99–100% at two years; no graft rejection or acute graft‑versus‑host disease was observed. These results exceeded the trial’s initial donor‑chimerism goal (>1% by day +42). (nature.com)
Why it matters for Fanconi anemia
Fanconi anemia is a DNA‑repair disorder that leads to progressive bone‑marrow failure; about 80% of patients show signs of marrow failure by age 12. Conventional conditioning with irradiation and high‑dose alkylators is especially toxic in this population and is associated with short‑ and long‑term complications, including secondary cancers. The antibody‑based approach aims to maintain transplant efficacy while reducing genotoxic exposure. (nature.com)
Voices from the team
“We were able to treat these really fragile patients with a new, innovative regimen that allowed us to reduce the toxicity,” said co‑senior author Agnieszka Czechowicz, MD, PhD. Co‑first author Rajni Agarwal, MD, called it “a novel approach” for highly vulnerable patients. (Both comments were made to Stanford Medicine’s News Center.) (med.stanford.edu)
A patient’s experience
Stanford Medicine identified the first child treated as 11‑year‑old Ryder Baker of Seguin, Texas, who underwent transplant at Lucile Packard Children’s Hospital Stanford in early 2022. His mother said he has far more energy now, noting “it’s completely different.” These family details come from Stanford’s News Center. (med.stanford.edu)
Donor access and technique
By enabling safe use of half‑matched relatives, the αβ T‑cell–depleted graft platform broadens donor options. Stanford notes that historically about 35–40% of patients who needed transplants did not receive them due to lack of a fully matched donor; the team’s approach is intended to address that barrier. (med.stanford.edu)
Cancer‑risk context
Stanford’s news release quotes Czechowicz as saying that “nearly all” Fanconi anemia patients develop secondary cancers by age 40. Published registry analyses report very high but variable risks: for example, studies have estimated cumulative solid‑tumor incidences around 28–30% by age ~40 and substantially higher by age 50. Transplant conditioning may further increase head‑and‑neck cancer risk in this population. (haematologica.org)
What’s next
A phase 2 expansion is under way (NCT04784052). Stanford says it will also study whether the antibody‑based conditioning can help in other marrow‑failure syndromes, such as Diamond‑Blackfan anemia, and explore less‑intensive options for some older cancer patients who cannot tolerate standard regimens. Briquilimab is supplied by Jasper Therapeutics. (dx.doi.org)
