Innovation In Bone Marrow Transplantation: Healing Blood Without Radiation Or Harsh Chemotherapy

A new type of bone marrow transplant has proven much safer for patients with serious blood diseases. Instead of using strong chemotherapy or radiation, scientists used an antibody that eliminates only the old marrow cells, making room for the donor's healthy cells. This method was tested in children with Fanconi anemia and yielded good results, with fewer side effects and stable blood recovery.

Hematopoietic stem cell transplantation, also known as bone marrow transplantation, is a treatment that can cure several blood diseases, both genetic and acquired, such as bone marrow failure, hereditary anemias, and some types of cancer. This treatment works by replacing the patient's diseased cells with healthy stem cells from a compatible donor.

The major challenge with this procedure is that, to receive the new cells, the patient's body must first be "prepared" with medications or radiation that destroy the old marrow cells, making room for the new ones.

This process, called conditioning, usually involves high doses of chemotherapy or radiation, which are very aggressive and can cause serious short- and long-term side effects, such as infertility, organ problems, and even an increased risk of developing other cancers in the future.

To circumvent these problems, researchers at Stanford University School of Medicine in the USA have been developing safer alternatives. In a recent study, a new protocol was created that does not use traditional radiation or certain highly toxic chemotherapy drugs. Instead, scientists used an antibody called briquilimab, also known as JSP191.

Antibodies are molecules capable of recognizing very specific targets, like a "key" that fits into a "lock." Briquilimab binds to a protein called CD117, which is present on the surface of blood stem cells. By blocking this protein, the antibody can selectively eliminate the patient's old stem cells without causing the same type of widespread damage that radiation or chemotherapy can cause.

In addition to this antibody, the researchers used drugs that reduce the activity of the immune system, such as rabbit antithymocyte globulin, cyclophosphamide, fludarabine, and rituximab.

These drugs prevent the patient's body from rejecting the donor cells and also help prevent complications such as graft-versus-host disease, which occurs when the transplanted cells attack the recipient organism.

The stem cells used in the transplant were also carefully prepared to remove a specific type of lymphocyte, which are immune system cells responsible for causing rejection and severe inflammation. This step significantly reduces the risk of complications after the procedure.

This protocol was initially tested on three children with Fanconi anemia, a rare genetic disease that impairs DNA repair mechanisms. People with this condition are extremely sensitive to radiation and chemotherapy, so they face even greater risks with traditional treatments.

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

In the clinical trial, the three children received transplants using this new protocol and were followed for two years. All of them recovered well, without severe rejection or major complications, and had stable blood and immune system reconstruction using the donor cells.

The results show that this innovative approach can maintain the effectiveness of the transplant while dramatically reducing the toxicity of the procedure.

Although testing has begun in people with Fanconi anemia, the expectation is that in the future, this strategy may also benefit patients with other blood diseases, including hematologic cancers. Research is currently in more advanced stages to confirm these findings in larger groups of patients.

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Irradiation- and busulfan-free stem cell transplantation in Fanconi anemia using an anti-CD117 antibody: a phase 1b trial

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

Nature Medicine. 22 July 2025

DOI: 10.1038/s41591-025-03817-1

Abstract: 

Current hematopoietic stem cell transplantation (HSCT) conditioning strategies cause widespread tissue damage and systemic toxicities, especially in patients with DNA-repair deficiencies such as Fanconi anemia (FA). We have developed an alternative conditioning approach that incorporates the anti-CD117 antibody, briquilimab, which targets host hematopoietic stem and progenitor cells in place of genotoxic irradiation- and busulfan-based chemotherapy. Here we report a phase 1b clinical trial in patients with FA and bone marrow failure, evaluating safety and efficacy of briquilimab-based conditioning in combination with rabbit anti-thymocyte globulin, cyclophosphamide, fludarabine and rituximab immunosuppression and T cell receptor (TCR)αβ+ T cell-depleted and CD19+ B cell-depleted haploidentical HSCT. Primary endpoints of the trial included safety and engraftment, and secondary endpoints included pharmacokinetic measures and hematological and immunological recovery. All three patients have each undergone 2 years of follow-up to complete the phase 1b analysis. No treatment-emergent adverse events or acute graft-versus-host disease was observed. Patients experienced minimal toxicities, with typical mucositis and no veno-occlusive disease. Median neutrophil engraftment was 11 days (range 11–13 days) with robust donor chimerism up to 2 years post-HSCT (99–100%), meeting the primary endpoints of the study. Briquilimab cleared in each patient before HSCT without the need for adjustment. Red blood cell, platelet and lymphocyte recovery was comparable to previous reports with TCRαβ+ T cell-depleted and CD19+ B cell-depleted grafts. All patients are alive and well with resolution of earlier chromosomal breakage abnormalities in peripheral blood lymphocytes post treatment. These data demonstrate the broad potential of this protocol in maintaining HSCT efficacy while reducing toxicity. The phase 2 trial is ongoing (ClinicalTrials.gov identifier: NCT04784052).