Stanford University makes stem cell transplants safer without chemotherapy

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

“We were able to treat these really vulnerable patients with a new and innovative regimen that allowed us to reduce the toxicity of the stem cell transplant protocol,” said Agnieszka Czechovich, MD, PhD, assistant professor of pediatrics and co-senior author of the study. “Specifically, we can stop using radiotherapy and genotoxic chemotherapy called busulfan, with exceptional results.”

The trial, published in Natural medicineused an antibody in combination with other drugs to enable successful organ transplants for three children with Fanconi anemia. The three patients have been followed for two years and are in good health.

“If they don’t get a transplant in time, the bodies of Fanconi anemia patients eventually won’t produce blood, so they die from bleeding or infection,” explained Rajni Agarwal, MD, professor of pediatric stem cell transplantation and co-first author. “The reason I’m so excited about this trial is because it’s a new way to help these patients, who are so vulnerable.”

Antibodies replace radiotherapy and chemotherapy

Before a stem cell transplant (in which unhealthy bone marrow is replaced with a healthy donor), doctors must get rid of the patient’s blood-forming stem cells. This usually involves radiation or chemotherapy. However, in this study, patients received antibodies targeting CD117, a protein found in hematopoietic stem cells.

The antibody, known as briquilimab, safely removed those cells without the harmful side effects of conventional treatments.

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

Czechovich began studying hematopoietic stem cells in 2004 as an undergraduate working with Irving Weissman, MD, then director of the Stanford 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 scientists at Stanford University, they were later able to identify a version suitable for human clinical use, leading to this latest trial.

Solve the donor matching problem

The clinical trial also addressed another major hurdle in stem cell transplants: the shortage of well-matched donors. In the past, up to 40% of patients could not receive organ transplants because a compatible donor could not be found.

To make the procedure more flexible, the researchers modified the donated bone marrow before the transplant. They enriched them for CD34+ cells (the donor’s blood-forming stem cells) while removing immune cells called alpha/beta T cells, which can cause a serious complication known as graft-versus-host disease. This method, invented by Dr. Alice Bertina, allows for safe transplants from mismatched donors, including parents.

“We are working to significantly expand donor pools for stem cell transplants, so that every patient who needs a transplant can get one,” Agarwal said.

Child Recovery: Ryder’s Story

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

Today, Ryder is thriving. His mother, Andrea Riley, said: “He was so tired, he didn’t have the stamina. It’s completely different now.” She added that her son Fanconi’s anemia “is no longer slowing him down like it used to.”

Now full of energy, Ryder recently finished fifth grade, plays sports, and even received the “Up and Coming Player” award from his school’s 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 common in blood cancers, where the bone marrow is full of malignant cells and patients have no other options,” Czechovich said. “But as we make these transplants better and safer, we can expand them to include 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 this 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 problem is that while stem cell transplants can prevent this failure, the usual preparatory chemotherapy or radiation can cause serious complications or even cancer.

“Currently, almost all of these patients develop secondary cancers by the time they reach 40,” Czechovich said. The team hopes that their new antibody-based approach will significantly reduce this risk.

Promising results in early patients

All three trial participants were less than 10 years old and had different genetic variants of Fanconi anemia. Each received a single dose of the antibody intravenously 12 days before transplantation, followed by standard immunosuppressive drugs 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 took root in the patients’ bone marrow. None of them experienced graft rejection, and one month after transplantation, the donor cells had almost completely replaced their own.

The research team initially aimed for only 1% donor cells. Two years later, all three children had achieved nearly 100% donor cell chimerism.

“We were surprised at how well it worked,” Czechovich said. “We were optimistic that we would get here, but you never know when you are trying a new system.”

Life after transplant

Even with the safer protocol, organ transplants are still required. Ryder spent more than a month in the hospital and suffered temporary fatigue, nausea and hair loss.

“It was heartbreaking to see him go through things like that — I would rather go through that than my own child,” Riley said. “I felt so sad for him, and now he doesn’t have to.”

Since his recovery, Ryder has grown taller, gained weight and is no longer constantly sick. “It hits hard when he gets sick at all, and I don’t have to worry about that anymore,” Riley said.

She also told her son that his experience as one of the first patients would help others. “I think he takes pride in it, too,” she said.

Next steps for Stanford research

After more than 30 years of using traditional methods, Agarwal said she is thrilled to offer families this new, less toxic option. “When I advise families, their eyes start to light up and they think: ‘Well, we can avoid radiation and chemical poisoning,'” she said.

The Stanford 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 kill cancer cells, researchers are also studying whether the antibody could benefit elderly cancer patients who cannot tolerate conventional conditioning.

“These residents are often at a disadvantage,” Agarwal said. “It may provide us with a way to treat them less intensively so they can get a transplant.”

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

Cooperation and support

In addition to Czechovich, Agarwal, and Bertina, the book is co-authored by Matthew Porteous, MD, PhD, and researchers from the University of California, San Francisco; Kaiser Permanente Bernard J. Tyson College of Medicine; St. Jude Children’s Research Hospital; Memorial Sloan Kettering Cancer Center; Jasper Therapeutics Inc. contributed. In the study.

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