Stanford Medicine researchers have achieved a breakthrough in stem cell transplantation by successfully treating three children with Fanconi anemia using a novel antibody-based protocol that eliminates the need for toxic radiation or chemotherapy. The phase 1 clinical trial, published in Nature Medicine on July 22, 2025, demonstrates that the anti-CD117 antibody briquilimab can safely prepare patients for transplantation while avoiding the severe side effects associated with traditional conditioning regimens.
"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," said Dr. Agnieszka Czechowicz, the study's co-senior author and assistant professor of pediatrics. "Specifically, we could eliminate the use of radiation and genotoxic chemotherapy called busulfan, with exceptional outcomes."
Revolutionary Approach to Stem Cell Conditioning
The traditional stem cell transplant process requires eliminating a patient's diseased bone marrow cells through radiation or chemotherapy before introducing healthy donor cells. For patients with Fanconi anemia, a genetic disorder affecting DNA repair mechanisms, this approach creates a dangerous paradox: while transplantation can be life-saving, the conditioning treatment itself poses extreme risks due to the patients' compromised DNA repair systems.
The Stanford team's solution targets CD117, a protein on the surface of blood-forming stem cells. Instead of using toxic treatments, patients received a single intravenous infusion of briquilimab 12 days before their scheduled transplant. This antibody specifically eliminates blood-forming stem cells without the hazardous side effects of conventional approaches.
Dr. Rajni Agarwal, co-first author and professor of pediatric stem cell transplantation, emphasized the urgency for these vulnerable patients: "If they don't get a transplant in time, Fanconi anemia patients' bodies eventually will not make blood, so they die of bleeding or infections."
Addressing Donor Shortage Through Innovation
The research team tackled a second critical challenge in stem cell transplantation: donor availability. Historically, 35% to 40% of patients requiring transplants could not receive them due to lack of fully matched donors. The Stanford protocol incorporates a technique developed by co-first author Dr. Alice Bertaina that modifies donated bone marrow by enriching for CD34+ cells while removing problematic alpha/beta T-cells.
This innovation reduces the risk of graft-versus-host disease, allowing patients to receive transplants from half-matched donors such as parents. "We are expanding the donors for stem cell transplantation in a major way, so every patient who needs a transplant can get one," Agarwal explained.
Exceptional Clinical Outcomes
The three trial participants, all under age 10 with different racial/ethnic backgrounds and varying Fanconi anemia gene mutations, demonstrated remarkable results. Within two weeks of transplantation, donated stem cells successfully engrafted in patients' bone marrow. By 30 days post-transplant, healthy donor cells had almost completely replaced the patients' original marrow.
The researchers initially aimed for 1% donor chimerism, but after two years, all three patients maintained close to 100% donor cell engraftment—far exceeding expectations. None experienced graft rejection, and all completed two years of follow-up with excellent outcomes.
"We've been surprised by how well it's worked," Czechowicz noted. "We were optimistic that we would get here, but you never know when you're trying a new regimen."
Patient Success Story
Ryder Baker of Seguin, Texas, now 11 years old, was the first patient to benefit from this approach when he received his transplant at Lucile Packard Children's Hospital Stanford in early 2022. His mother, Andrea Reiley, described the transformation: "He was so tired, he didn't have stamina. It's completely different now."
Since his transplant, Ryder has grown taller, gained weight, and become significantly less susceptible to infections. He now actively participates in sports, including pickleball, and recently received an "Up and Coming Player" award from his school's soccer team.
Understanding Fanconi Anemia
Fanconi anemia disrupts DNA repair mechanisms, leading to impaired blood cell development including red blood cells, white blood cells, and platelets. Patients experience fatigue, reduced growth, frequent infections, and excessive bruising and bleeding. Progressive bone marrow failure develops in approximately 80% of patients by age 12, creating a life-threatening condition.
The disease creates a treatment dilemma: while stem cell transplants can prevent bone marrow failure, patients' defective DNA repair makes them extremely vulnerable to secondary cancers from traditional conditioning treatments. "Right now, nearly all of these patients get secondary cancers by the time they're 40," Czechowicz said, expressing hope that their new approach will reduce these rates.
Future Applications and Ongoing Research
The research team is currently conducting a phase 2 trial with additional Fanconi anemia patients and planning studies for other conditions, including Diamond-Blackfan anemia, another genetic disease causing bone marrow failure. They are also exploring applications for elderly cancer patients who cannot tolerate full-intensity conditioning regimens.
"That population is often at a disadvantage," Agarwal noted. "It may provide us with a way to treat them with less intensity so it's possible for them to get a transplant."
The work builds on decades of Stanford Medicine research, beginning with Dr. Czechowicz's undergraduate studies in 2004 under Dr. Irving Weissman, focusing on CD117's role in stem cell regulation. The team identified that anti-CD117 antibodies could eliminate stem cells in mice without radiation or chemotherapy toxicity, leading to the clinical antibody equivalent used in this trial.
While most cancer patients may still require some chemotherapy or radiation to eliminate malignant cells, the researchers believe their approach could significantly benefit fragile patient populations. As they continue developing next-generation treatments, this breakthrough represents a paradigm shift toward safer, more accessible stem cell transplantation for patients with genetic diseases.
