\u201cBone 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,\u201d Czechowicz said. \u201cBut as we\u2019re making these transplants better and safer, we can expand them to more patients including those with many different diseases.\u201d<\/p>\n
A disease of DNA repair<\/p>\n
Fanconi anemia interferes with DNA repair. One consequence is impaired development of blood cells, including oxygen-carrying red blood cells; white blood cells needed for immune function; and platelets, which help the blood clot. Patients experience fatigue, reduced growth, frequent infections, and more bruising and bleeding than normal. Eventually, their blood cell production is so diminished they have a life-threatening condition known as progressive bone marrow failure, signs of which develop in about 80% of Fanconi anemia patients by age 12.<\/p>\n
Children with Fanconi anemia can become stuck in a catch-22: A stem cell transplant can prevent and treat bone marrow failure, but because their DNA-repair machinery works so poorly, patients are extremely vulnerable to side effects \u2014 including cancer \u2014 from the chemotherapy or radiation used to prepare for these transplants.<\/p>\n
\u201cRight now, nearly all of these patients get secondary cancers by the time they\u2019re 40,\u201d Czechowicz said, adding that her team hopes their new approach will reduce those rates. Fanconi anemia patients are also more vulnerable than other people to complications of graft-versus-host disease.<\/p>\n
The three trial participants were all younger than 10 when they received their transplants. They were of different racial\/ethnic backgrounds and had different gene mutations underlying their Fanconi anemia.<\/p>\n
Each patient received a single intravenous infusion of the antibody 12 days before they were scheduled to receive donated stem cells. Closer to the transplant date, they received immune-suppressing medications typically given before stem cell transplant, but no radiation or busulfan chemotherapy that is typically part of the treatment regimen.<\/p>\n
Each patient was then given a stem cell transplant consisting of cells that had been donated by a parent, depleted of alpha\/beta T-cells and enriched for blood-forming stem cells. Within two weeks, the donated stem cells quickly took up residence in the patients\u2019 bone marrow. No one experienced graft rejection \u2014 a transplant complication in which the patient\u2019s immune system rejects the donated cells \u2014 and by 30 days after transplant, the healthy cells from the donors had almost completely taken over the patients\u2019 marrow.<\/p>\n
The researchers\u2019 initial goal was to help patients reach 1% donor chimerism, meaning 1% of the bone marrow cells would come from the donor. But two years later, all three patients have close to 100% of their cells from their donors \u2014 far better than the researchers expected.<\/p>\n
\u201cWe\u2019ve been surprised by how well it\u2019s worked,\u201d Czechowicz said. \u201cWe were optimistic that we would get here, but you never know when you\u2019re trying a new regimen.\u201d<\/p>\n
A medical pioneer<\/p>\n
Even with the improved protocol, a stem cell transplant is a big challenge for kids like Ryder, requiring them to spend more than a month in the hospital and endure short-term side effects such as severe exhaustion, nausea and hair loss.<\/p>\n
\u201cIt was heartbreaking to see him go through things like that \u2014 I\u2019d rather go through it than my child,\u201d Reiley said, adding that, fortunately, Ryder remembers little of the experience. \u201cI felt the heartbreak for him, and now he doesn\u2019t have to.\u201d<\/p>\n
Since his transplant, Ryder has grown taller, gained weight and become much less susceptible to run-of-the-mill germs, his mom said. \u201cIt used to be huge hits when he would get sick at all, and I really don\u2019t have to worry about that anymore.\u201d<\/p>\n
Reiley has conversations with her son about how his experience as a medical pioneer is helping experts take better care of other kids. \u201cI think he takes a lot of pride in that, too,\u201d she said.<\/p>\n
After more than three decades of administering stem cell transplants with the traditional approach, Agarwal said she loves explaining to patients\u2019 families how much better the new options are.<\/p>\n
\u201cWhen I counsel families, their eyes start to shine as they think, \u2018OK, we can avoid the radiation and chemo toxicity\u2019,\u201d she said.<\/p>\n
The researchers are now conducting a phase 2 trial of the same protocol in additional children with Fanconi anemia. They also plan studies to test whether the new approach will work for other conditions, including Diamond-Blackfan anemia, another genetic disease that causes bone marrow failure.<\/p>\n
Most cancer patients may still require some chemotherapy or radiation to rid them of malignant cells, said the researchers, who noted that another team at Stanford Medicine is testing whether the antibody can help elderly cancer patients who can\u2019t tolerate full doses of radiation or chemotherapy because they are fragile or have diseases in addition to cancer.<\/p>\n
\u201cThat population is often at a disadvantage,\u201d Agarwal said. \u201cIt may provide us with a way to treat them with less intensity so it\u2019s possible for them to get a transplant.\u201d<\/p>\n
The group is also working on next-generation approaches that may continue to improve the treatment regimen for patients with Fanconi anemia as well as other grievous diseases.<\/p>\n
Other researchers who contributed to the study were from the University of California, San Francisco; Kaiser Permanente Bernard J. Tyson School of Medicine; St. Jude Children\u2019s Research Hospital; Memorial Sloan Kettering Cancer Center; and Jasper Therapeutics Inc.<\/p>\n
Study funding came from anonymous philanthropic support and the California Institute of Regenerative Medicine. The antibody, briquilimab, was supplied by Jasper Therapeutics Inc. The Fanconi Cancer Foundation and the Stanford Clinical Trial program also provided clinical trial support and assisted with the execution of the study.<\/p>\n