Stanford Research Advances Stem Cell Transplants Without Chemotherapy

A new antibody therapy developed at Stanford Medicine has demonstrated the potential to prepare patients for stem cell transplants without the conventional use of toxic chemotherapy or radiation. This breakthrough, reported in a phase one clinical trial published in Nature Medicine, focuses on children with Fanconi anemia, a rare genetic disorder that complicates traditional stem cell transplants.

Dr. Agnieszka Czechowicz, assistant professor of pediatrics and co-senior author of the study, stated, 'We were able to treat these really fragile patients with a new, innovative regimen that allowed us to reduce the toxicity of the stem cell transplant protocol.' The trial involved three children who received an antibody, briquilimab, targeting CD117, a protein found on blood-forming stem cells, thus eliminating the need for radiation and genotoxic chemotherapy such as busulfan.

All three patients have been followed for two years with positive outcomes. Dr. Rajni Agarwal, professor of pediatric stem cell transplantation and co-first author, explained that Fanconi anemia leads to severe complications if transplants are not received in time.

The antibodies were administered twelve days before the transplant, successfully allowing the new stem cells to take root without graft rejection. Remarkably, within a month post-transplant, the donor cells had nearly fully replaced the patients' own blood-forming stem cells, achieving nearly one hundred percent donor cell chimerism after two years.

This innovative approach not only addresses the challenges of chemotherapy-induced complications but also tackles the issue of donor shortages by modifying donor bone marrow to allow for half-matched transplants.

The first patient treated was Ryder Baker, an eleven-year-old boy from Texas, who is now thriving and enjoying life after overcoming the severe fatigue associated with his condition. Researchers are excited about the implications for expanding stem cell transplants to more patients with Fanconi anemia and potentially other inherited disorders.

They are now leading a phase two clinical trial to further explore this approach and evaluate its effectiveness in other conditions. The research was supported by numerous institutions and donors, including the California Institute of Regenerative Medicine and the Fanconi Cancer Foundation.

This advancement could significantly reshape the landscape of pediatric stem cell treatments, providing safer options for vulnerable patients.