The study focused on patients with Fanconi anemia, a rare genetic disorder that makes traditional stem cell transplants extremely dangerous. Researchers believe the same method could also be used for people with other inherited diseases that require transplants.

"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 Agnieszka Czechowicz, MD, PhD, assistant professor of pediatrics and co-senior author of the study. "Specifically, we could eliminate the use of radiation and genotoxic chemotherapy called busulfan, with exceptional outcomes."

The trial, published in Nature Medicine, used an antibody in combination with other drugs to enable successful transplants for three children with Fanconi anemia. All three patients have now been followed for two years and are doing well.

"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," explained Rajni Agarwal, MD, professor of pediatric stem cell transplantation and co-first author. "The reason I am so excited about this trial is that it is a novel approach to help these patients, who are very vulnerable."

Antibody Replaces Radiation and Chemotherapy

Before a stem cell transplant (in which unhealthy bone marrow is replaced with a healthy donor's), doctors must eliminate the patient's own blood-forming stem cells. Normally, this involves radiation or chemotherapy. In this study, however, patients received antibodies targeting CD117, a protein found on blood-forming stem cells.

The antibody, known as briquilimab, safely removed those cells without the damaging side effects of traditional conditioning treatments.

This new success builds on decades of Stanford Medicine research aimed at making stem cell transplants safer and more widely available.

Czechowicz began studying blood-forming stem cells in 2004 as an undergraduate working with Irving Weissman, MD, then director of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. Their early studies showed that blocking CD117 with antibodies could eliminate stem cells in mice without using radiation or chemotherapy. Working with other Stanford scientists, they later identified a version suitable for human clinical use, leading to this recent trial.

Solving the Donor Match Problem

The clinical trial also tackled another major hurdle in stem cell transplants: the shortage of fully matched donors. In the past, up to 40% of patients couldn't receive transplants because no compatible donor could be found.

To make the procedure more flexible, researchers modified donor bone marrow before transplantation. They enriched it for CD34+ cells (the donor's blood-forming stem cells) while removing immune cells called alpha/beta T-cells, which can cause a dangerous complication known as graft-versus-host disease. This method, pioneered by Alice Bertaina, MD, PhD, allows safe transplants from half-matched donors, including 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 said.

A Child's Recovery: Ryder's Story

The first patient to receive the treatment was Ryder Baker, an 11-year-old from Seguin, Texas. He underwent the transplant at Lucile Packard Children's Hospital Stanford in early 2022.

Today, Ryder is thriving. "He was so tired, he didn't have stamina. It's completely different now," said his mother, Andrea Reiley. She added that her son's Fanconi anemia "doesn't slow him down like it used to."

Now full of energy, Ryder recently finished fifth grade, plays sports, and even received an "Up and Coming Player" award from his school soccer team.

Hope for More Patients

Researchers hope Ryder will be the first of many children to benefit. "Bone marrow or stem cell transplants are most commonly used in blood cancers, in which the bone marrow is full of malignant cells and patients have no other options," said Czechowicz. "But as we're making these transplants better and safer, we can expand them to more patients including those with many different diseases."

Understanding Fanconi Anemia

Fanconi anemia affects the body's ability to repair DNA damage, disrupting the production of vital blood cells such as red blood cells, white blood cells, and platelets. Children with the condition often experience fatigue, poor growth, frequent infections, and excessive bruising or bleeding.

By age 12, about 80% develop progressive bone marrow failure, which can be fatal if left untreated. The catch-22 is that while stem cell transplants can prevent this failure, the usual preparative chemotherapy or radiation can cause severe complications or even cancer.

"Right now, nearly all of these patients get secondary cancers by the time they're 40," Czechowicz said. The team hopes their new antibody-based approach will sharply lower that risk.

Promising Results in Early Patients

All three trial participants were under 10 years old and had different genetic variants of Fanconi anemia. Each received one intravenous dose of the antibody 12 days before their transplant, followed by standard immune-suppressing medication but no busulfan or radiation.

The donated stem cells came from a parent and were carefully processed to remove harmful immune cells. Within two weeks, the new stem cells had taken root in the patients' bone marrow. None experienced graft rejection, and by one month after transplant, donor cells had nearly fully replaced their own.

The research team had initially aimed for just 1% donor cell presence. Two years later, all three children reached nearly 100% donor cell chimerism.

"We've been surprised by how well it's worked," Czechowicz said. "We were optimistic that we would get here, but you never know when you're trying a new regimen."

Life After Transplant

Even with the safer protocol, transplants remain demanding. Ryder spent over a month in the hospital and experienced temporary exhaustion, nausea, and hair loss.

"It was heartbreaking to see him go through things like that -- I'd rather go through it than my child," Reiley said. "I felt the heartbreak for him, and now he doesn't have to."

Since recovery, Ryder has grown taller, gained weight, and is no longer constantly sick. "It used to be huge hits when he would get sick at all, and I really don't have to worry about that anymore," Reiley said.

She also tells her son that his experience as one of the first patients will help others. "I think he takes a lot of pride in that, too," she said.

Next Steps for Stanford's Research

After more than 30 years of using traditional methods, Agarwal said she's thrilled to offer families this new, less toxic option. "When I counsel families, their eyes start to shine as they think, 'OK, we can avoid the radiation and chemo toxicity'," she said.

Stanford's team is now leading a phase 2 clinical trial in more children with Fanconi anemia. They also plan to explore whether the antibody approach could help patients with other rare bone marrow failure disorders such as Diamond-Blackfan anemia.

While most cancer patients will still need some chemotherapy or radiation to eliminate cancer cells, researchers are also studying whether the antibody can benefit elderly cancer patients who can't tolerate traditional conditioning.

"That population is often at a disadvantage," Agarwal said. "It may provide us with a way to treat them with less intensity so it's possible for them to get a transplant."

The team is also developing next-generation antibody-based treatments to further refine and improve outcomes for Fanconi anemia and similar diseases.

Collaboration and Support

In addition to Czechowicz, Agarwal, and Bertaina, co-senior author Matthew Porteus, MD, PhD, and researchers from the University of California, San Francisco; Kaiser Permanente Bernard J. Tyson School of Medicine; St. Jude Children's Research Hospital; Memorial Sloan Kettering Cancer Center; and Jasper Therapeutics Inc. contributed to the study.

The research received funding from anonymous donors, the California Institute of Regenerative Medicine, and the Fanconi Cancer Foundation. Jasper Therapeutics provided the antibody briquilimab, and the Stanford Clinical Trial Program supported the study's implementation.