In a recent clinical trial, patients with B-acute lymphoblastic leukemia (B-ALL) who had no measurable residual disease (MRD) after prior treatment showed similar outcomes whether they received chemotherapy-based conditioning or the standard total body irradiation (TBI) before hematopoietic cell transplantation. This research suggests that some patients may be able to avoid TBI and its associated long-term side effects.
The study is notable for being the first to evaluate chemotherapy-based conditioning in patients confirmed as MRD-negative through next-generation sequencing (NGS) before starting the transplant process. The trial achieved its primary goal, demonstrating a two-year relapse-free survival rate comparable to an observational group of patients who underwent TBI-based conditioning.
B-ALL is a cancer affecting the bone marrow and leads to an excess of abnormal B-cells, which are a type of white blood cell. It remains the most common form of childhood leukemia and is also prevalent among adults diagnosed with acute lymphoblastic leukemia. Allogeneic hematopoietic cell transplantation offers a potential cure for B-ALL, especially for those at high risk of relapse. Before transplantation, patients typically undergo intensive chemotherapy and radiation therapy to prepare their bone marrow for new cells. While previous studies have indicated that TBI-based regimens generally produce better results than chemotherapy alone, TBI can result in lasting negative effects on memory, hormone function, and increase the risk of future cancers.
The researchers used NGS-MRD testing based on IgH B-cell receptor rearrangements to identify candidates without detectable cancer cells, hypothesizing these individuals could safely receive chemotherapy-only conditioning without increased relapse risk.
A total of 51 MRD-negative patients participated in the study and underwent transplants following chemotherapy-based conditioning. The age range at diagnosis was from 2 to 30 years old, with a median age of 13.5 years; half were male. At the time of transplant, half were in their first complete remission while the other half were in their second remission after initial treatments.
Participants have been monitored for a median period of 2.3 years—ranging from several months up to six years—and their outcomes were compared with those from an observational cohort of 151 patients who received standard TBI conditioning.
After just over two years, data showed that 82% of those given chemotherapy-based conditioning were alive; 76.3% remained alive without experiencing a relapse. Twelve percent died from causes unrelated to cancer relapse, and another 12% experienced disease recurrence.
Event-free survival and overall survival rates did not differ significantly between those receiving TBI and non-TBI regimens.
Researchers noted that NGS-MRD testing may serve as an effective biomarker for identifying which patients could avoid TBI safely. "This study really sets a new standard of care for those patients," said Dr. Abdel-Azim. "Using this guided approach, patients who are NGS-MRD negative prior to transplant could be getting non-TBI based conditioning."
Graft-versus-host-disease (GVHD), where transplanted cells attack the patient’s own tissues, occurred in some participants: 10% experienced severe acute GVHD (grades 3-4), while chronic GVHD requiring systemic treatment developed in 21%.
Outcomes were worse among younger children at diagnosis or transplant time; however, among NGS-MRD negative individuals, both high-risk and non-high-risk genetic groups had similar results.
Researchers plan further studies into genetic factors and other variables influencing outcomes so they can better tailor pre-transplant regimens according to each patient's risk profile.
The Gateway for Cancer Research funded this study.
Dr. Hisham Abdel-Azim from Loma Linda University School of Medicine Cancer Center will present these findings on Saturday, December 6, 2025 at noon Eastern time at W331 in the Orange County Convention Center.
