New Antibody Therapy Offers Hope for Safer Stem Cell Transplants in Fanconi Anemia

A groundbreaking antibody therapy developed at Stanford Medicine is offering a potentially life-saving alternative to traditional, toxic conditioning treatments for children with Fanconi anemia (FA) undergoing stem cell transplants. The new approach, detailed in a phase 1 clinical trial, replaces chemotherapy and radiation with a targeted antibody, significantly reducing the risks associated with this critical treatment.

Understanding Fanconi Anemia

Fanconi anemia is a rare, inherited genetic disorder that impairs the body’s ability to repair DNA damage. This leads to a decline in the production of vital blood cells – red blood cells, white blood cells, and platelets – resulting in fatigue, poor growth, frequent infections, and a heightened risk of bleeding. Without treatment, progressive bone marrow failure typically develops by age 12, often proving fatal.

The Challenge of Stem Cell Transplants

While stem cell transplantation offers the most effective treatment for FA, the process traditionally involves preparing the patient’s body with high doses of chemotherapy or radiation to eliminate existing blood-forming stem cells and build way for the donor cells. These treatments, however, can cause severe and lasting side effects, including tissue damage and an increased risk of secondary cancers. Currently, nearly all patients develop secondary cancers by the time they are 40 years ancient.

A New Approach: Briquilimab and Targeted Antibody Therapy

Researchers at Stanford Medicine have pioneered a new method utilizing an antibody called briquilimab. This antibody specifically targets CD117, a protein found on blood-forming stem cells, effectively removing them without the damaging effects of radiation or chemotherapy.

In the phase 1 clinical trial, three children with Fanconi anemia received a single intravenous dose of briquilimab 12 days before their stem cell transplant, followed by standard immunosuppressive medication. The transplanted stem cells came from a parent and were processed to remove immune cells that could cause graft-versus-host disease. Within two weeks, the new stem cells successfully took root in the patients’ bone marrow, and after two years, all three children have achieved nearly 100% donor cell chimerism – meaning their blood is now almost entirely derived from the donor cells.

Expanding Donor Options

The new protocol as well addresses another significant challenge in stem cell transplantation: finding a fully matched donor. Researchers modified donor bone marrow before transplantation, enriching it with CD34+ cells (the donor’s blood-forming stem cells) while removing alpha/beta T-cells, which can cause graft-versus-host disease. This allows for safe transplants from half-matched donors, such as parents, significantly increasing the pool of potential donors.

Ryder’s Story: A Life Transformed

Ryder Baker, an 11-year-old from Texas, was the first patient to receive the antibody-based treatment at Lucile Packard Children’s Hospital Stanford in early 2022. Before the transplant, Ryder suffered from fatigue and lacked stamina. Today, he is thriving, playing sports, and excelling in school. His mother, Andrea Reiley, reports a dramatic improvement in his energy levels and overall health.

Future Directions and Potential Applications

Stanford’s research team is now conducting a phase 2 clinical trial involving more children with Fanconi anemia. They are also exploring the potential of this antibody approach for other rare bone marrow failure disorders, such as Diamond-Blackfan anemia. Researchers are investigating whether the antibody could benefit elderly cancer patients who are unable to tolerate traditional conditioning treatments.

“We are expanding the donors for stem cell transplantation in a major way, so every patient who needs a transplant can receive one,” said Agnieszka Czechowicz, MD, PhD, assistant professor of pediatrics and co-senior author of the study.