MANY PEOPLE WITH B-CELL acute lymphoblastic leukemia (ALL) at high risk of relapse receive total body irradiation along with high-dose chemotherapy prior to receiving a stem cell transplant. This conditioning regimen makes room in the bone marrow for donor cells and suppresses the immune system to lower the risk of transplant rejection. However, total body irradiation can come with long-term health risks, including infertility, hormone disorders and a second cancer.

Early findings from an ongoing phase II clinical trial presented Dec. 6, 2025, at the American Society of Hematology Annual Meeting and Exposition in Orlando, Florida, suggest children, adolescents and young adults with no measurable residual disease after chemotherapy may avoid total body irradiation prior to stem cell transplantation. In the trial, people who received chemotherapy-based conditioning had disease-free survival rates similar to those previously seen in people who received total body irradiation.

“This study is really the first to test the use of chemotherapy-based conditioning in patients with no evidence of measurable, minimal residual disease, or MRD, which is a very sensitive method to detect residual leukemia by a technology called next-generation sequencing MRD, before starting the pretransplant conditioning regimen,” says lead author Hisham Abdel-Azim, chief of transplant and cellular therapy at Loma Linda University Cancer Center in California.

About 15% to 20% of children with ALL—B-cell ALL is the most common type of childhood leukemia—experience recurrence. This is because some leukemia cells can remain after treatment, but next-generation sequencing can help better pinpoint malignant cells, Abdel-Azim says.

“You can think of this as thumbprinting the leukemia,” Abdel-Azim says. “You use those identified sequences to be able to identify any hidden or residual leukemia cells that you cannot identify by looking under the microscope or by standard methods that we currently use.”

The trial included 51 people ages 2 to 30 at diagnosis, with a median age of 13.5, who had undergone initial treatment and were preparing to receive a stem cell transplant. They tested negative for MRD, as determined by next-generation sequencing. About half were in their first complete remission, and half were in their second. Patients received chemotherapy-based conditioning, then a transplantation.

After a median follow-up of 2.3 years, 76.3% of patients remained disease-free, and 82% were alive. These results are comparable to historical data from patients who received total body irradiation, Abdel-Azim says.

The findings could potentially change treatment plans for young people, according to Mariam Nawas, a hematologist-oncologist at UChicago Medicine Comprehensive Cancer Center. She specializes in stem cell transplants in adults with various blood cancers.

“It’s the type of research that I think we just need to be thinking more about and doing more of—looking for opportunities when you can de-escalate very high-toxicity therapies without coming at the expense of efficacy,” says Nawas, who was not involved with the study. Children who receive total body irradiation can face, in addition to hormone disruption and infertility, side effects associated with skeletal and intellectual development.

Research on total body irradiation in adults has not been conclusive, so doctors already choose chemotherapy over total body irradiation for many people past young adulthood, Nawas says. But she says more research is needed to determine if adults who are MRD positive might benefit from irradiation.

“We’re already hesitant, to begin with, to use high-dose, irradiation-based transplants,” Nawas says. “If the radiation is toxic to young people, it’s only going to be more toxic to older adults.”

Anurag Singh, a hematologist-oncologist at the University of Kansas Cancer Center in Kansas City, says the trial demonstrates the potential of next-generation sequencing, which can detect 1 cancer cell among 1 million healthy cells. Among established techniques for measuring residual disease, such as flow cytometry, even the most sensitive tests can detect only 1 cancer cell in 100,000 healthy cells.

“If we can improve our tools of detection of even the smallest amount of cancer, we may be able to identify patients who are in deeper remission,” says Singh, who was not involved in the study. “Or we can identify people who we thought were in remission but [are] not really in remission.”

Chemotherapy comes with its own side effects, and 21% of trial participants experienced chronic graft-versus-host disease, a side effect of transplantation in which donor cells attack a patient’s healthy cells.

People should consider that this study was not a randomized controlled trial, which would compare the treatments head-to-head and provide stronger evidence, says Carl Shultz, a hematologist-oncologist at VCU Massey Comprehensive Cancer Center in Richmond, Virginia, who was not involved in the research. And because patients had tested negative for residual disease, they were already positioned to have an optimal outcome, regardless of conditioning type, he adds. Still, Shultz praises the trial’s geographic diversity, which included nearly 50 treatment centers across about two dozen states and Alberta, Canada.

“It means we have options,” Shultz says. “It’s important to know that there are non-radiation-based treatment options in the right patient population.”