{"id":168763,"date":"2025-08-23T09:08:10","date_gmt":"2025-08-23T09:08:10","guid":{"rendered":"https:\/\/www.europesays.com\/us\/168763\/"},"modified":"2025-08-23T09:08:10","modified_gmt":"2025-08-23T09:08:10","slug":"stem-cell-transplants-without-toxic-chemo-or-radiation","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/168763\/","title":{"rendered":"Stem Cell Transplants Without Toxic Chemo or Radiation"},"content":{"rendered":"

\t\t\"Stem<\/a>A Stanford Medicine team has developed a novel antibody-based approach that prepares patients for stem cell transplants without relying on toxic chemotherapy or radiation. Credit: Stock<\/p>\n

A Phase 1 clinical trial has shown that an antibody developed at Stanford Medicine can prepare patients for stem cell transplantation while avoiding toxic side effects.<\/strong><\/p>\n

A phase 1 clinical trial has demonstrated that an antibody treatment created at Stanford Medicine can safely prepare patients for stem cell transplants without the need for busulfan chemotherapy or radiation, both of which are highly toxic.<\/p>\n

The trial focused on children with Fanconi anemia, a rare genetic disorder that makes conventional stem cell transplantation especially dangerous. Although the study tested this new protocol in Fanconi patients, the researchers believe it could also benefit people with other genetic conditions that require transplants.<\/p>\n

\u201cWe 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,\u201d said co-senior author Agnieszka Czechowicz, MD, PhD, assistant professor of pediatrics. \u201cSpecifically, we could eliminate the use of radiation and genotoxic chemotherapy called busulfan, with exceptional outcomes.\u201d<\/p>\n

Published online July 22 in Nature Medicine, the trial used an antibody-based approach, in combination with other drugs, to carry out transplants for three children with Fanconi anemia. Each patient has now been followed for two years and is doing well.<\/p>\n

\u201cIf they don\u2019t get a transplant in time, Fanconi anemia patients\u2019 bodies eventually will not make blood, so they die of bleeding or infections,\u201d explained co-first author Rajni Agarwal, MD, professor of pediatric stem cell transplantation. \u201cThe reason I am so excited about this trial is that it is a novel approach to help these patients, who are very vulnerable.\u201d<\/p>\n

\"Agnieszka<\/a>Agnieszka Czechowicz sits at a flow cytometer. Her team used flow cytometry to study healthy and diseased bone marrow cells and to monitor the cells before, during and after an innovative form of stem cell transplant. Credit: Jim Gensheimer<\/p>\n

Normally, before a transplant can take place, diseased bone marrow must be cleared out, usually through chemotherapy or radiation. In this study, however, patients instead received antibodies targeting CD117, a protein found on blood-forming stem cells. The antibody, known as briquilimab, successfully eliminated the patients\u2019 stem cells without causing the toxic side effects associated with traditional conditioning treatments.<\/p>\n

Other authors of the study included co-first author Alice Bertaina, MD, PhD, the Lorry I. Lokey Professor, and co-senior author Matthew Porteus, MD, PhD, the Sutardja Chuk Professor in Definitive and Curative Medicine.<\/p>\n

Decades of research leads to safer transplant<\/p>\n

The Stanford Medicine researchers built on decades of discoveries to design a safer and more widely accessible method for stem cell transplantation.<\/p>\n

\"Rajni<\/a>Rajni Agarwal. Credit: Stanford Medicine<\/p>\n

Czechowicz began studying blood-forming stem cells in 2004, as an undergraduate in the laboratory of Irving Weissman, MD, the Virginia and D.K. Ludwig Professor in Clinical Investigation in Cancer Research and then-director of Stanford\u2019s Institute for Stem Cell Biology and Regenerative Medicine. Their early work examined CD117, a protein that controls stem cell growth and development. They demonstrated that an antibody targeting CD117 could block the growth of these cells and eliminate them in mice without exposing the animals to the dangers of chemotherapy or radiation. Working with other Stanford scientists, they later identified the clinical antibody version now used in the current trial.<\/p>\n

The trial also addressed a second barrier to transplantation. In the past, roughly 35% to 40% of patients who required a stem cell transplant were unable to receive one because they lacked a fully matched donor. To overcome this, researchers altered the donated bone marrow before transplant. They enriched it with CD34+ blood-forming stem cells and removed alpha\/beta T-cells, a type of immune cell that can trigger graft-versus-host disease \u2014 a condition in which donor immune cells attack the recipient. This approach, first developed by Bertaina and colleagues prior to her arrival at Stanford, makes it possible to use half-matched donors, such as a parent, greatly increasing the donor pool.<\/p>\n

\u201cWe are expanding the donors for stem cell transplantation in a major way, so every patient who needs a transplant can get one,\u201d explained Rajni Agarwal, MD.<\/p>\n

The first patient to benefit from these advances was Ryder Baker, an 11-year-old from Seguin, Texas. Ryder underwent a stem cell transplant at Lucile Packard Children\u2019s Hospital Stanford in early 2022 as part of the trial. Since then, his condition has improved dramatically. \u201cHe was so tired, he didn\u2019t have stamina. It\u2019s completely different now,\u201d said his mother, Andrea Reiley, adding that Fanconi anemia \u201cdoesn\u2019t slow him down like it used to.\u201d<\/p>\n

Now in sixth grade, Ryder has been channeling his renewed energy into athletics. He enjoys pickleball and was named \u201cUp and Coming Player\u201d on his school\u2019s soccer team.<\/p>\n

The researchers hope Ryder will be the first of many children whose lives are transformed by this approach.<\/p>\n

\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

\"Ryder<\/a>Ryder Baker has been able to play sports since his stem cell transplant. Credit: Lifetouch<\/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

Reference: \u201cIrradiation- and busulfan-free stem cell transplantation in Fanconi anemia using an anti-CD117 antibody: a phase 1b trial\u201d by Rajni Agarwal, Alice Bertaina, Charmaine Soco, Janel R. Long-Boyle, Gopin Saini, Nivedita Kunte, Lyndsie Hiroshima, Yan Y. Chan, Hana Willner, Mark R. Krampf, Rofida Nofal, Giulia Barbarito, Sushmita Sen, Maite Van Hentenryck, Emily Walck, Amelia Scheck, Rhonda J. Perriman, Alisha Bouge, Elena Istomina, Hena Naz Din, Edna F. Klinger, Jerry C. Cheng, Marcin W. Wlodarski, Jaap J. Boelens, Judith A. Shizuru, Wendy W. Pang, Kenneth Weinberg, Robertson Parkman, Maria Grazia Roncarolo, Matthew Porteus and Agnieszka Czechowicz, 22 July 2025, Nature Medicine.
DOI: 10.1038\/s41591-025-03817-1<\/a><\/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

Never miss a breakthrough: Join the SciTechDaily newsletter.<\/a><\/b><\/p>\n","protected":false},"excerpt":{"rendered":"A Stanford Medicine team has developed a novel antibody-based approach that prepares patients for stem cell transplants without…\n","protected":false},"author":3,"featured_media":168764,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8],"tags":[19635,95796,25763,159,3972,54158,67,132,68],"class_list":{"0":"post-168763","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-science","8":"tag-disease","9":"tag-immunology","10":"tag-pediatrics","11":"tag-science","12":"tag-stanford-university","13":"tag-stem-cells","14":"tag-united-states","15":"tag-unitedstates","16":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115077297470739222","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/168763","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=168763"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/168763\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/168764"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=168763"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=168763"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=168763"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}