Chemotherapy and radiation are comparable as pre-transplant conditioning for patients with b-acute lymphoblastic leukemia who have no measurable residual disease

(Press-News.org) (ORLANDO, Dec. 6, 2025) In a new trial, patients with B-acute lymphoblastic leukemia (B-ALL) who had no evidence of remaining cancer cells after prior treatment, experienced comparable outcomes whether they received chemotherapy-based conditioning or total body irradiation (TBI), the standard conditioning regimen used before hematopoietic cell transplantation. The findings could allow more patients to avoid TBI and its associated long-term side effects.

The study is the first to test the use of chemotherapy-based conditioning in patients with no evidence of measurable residual disease (MRD) through next-generation-sequencing (NGS) before starting the pre-transplant conditioning process. The trial met its primary endpoint with a two-year relapse-free survival rate comparable to that of an observational cohort of patients who received TBI-based conditioning.

“We used NGS-MRD – a very sensitive method to identify any residual leukemia cells in the patient – to categorize patients who are at very low risk for relapse and pilot the use of non-TBI-based conditioning versus the standard TBI conditioning,” said lead study author Hisham Abdel-Azim, MD, division chief for transplant/cell therapy and hematological malignancies and professor of pediatrics, medicine and basic sciences at Loma Linda University School of Medicine in California. “Using our approach, we were able to save a significant portion of patients who were MRD-negative before transplant from having to receive TBI without compromising their outcome.”

B-ALL is a cancer of the bone marrow that causes a buildup of abnormal B-cells, a type of white blood cell. It is the most common type of childhood leukemia and most common subtype of ALL in adults. Allogeneic hematopoietic cell transplantation is a curative treatment for B-ALL that is commonly recommended for patients at high risk for relapse. Before a transplant, patients must undergo a conditioning regimen of intensive chemotherapy and radiation to clear the bone marrow and make space for the transplanted cells. Although previous studies suggest TBI-based conditioning results in better outcomes than chemotherapy conditioning in general, TBI is also associated with long-term detrimental impacts on memory, endocrine function, and subsequent cancers. 

The study used NGS of IgH B-cell receptor rearrangements (NGS-MRD) to identify patients who have no detectable cancer, which researchers hypothesized would make them good candidates for chemotherapy-based conditioning without raising the risk of relapse.

In total, 51 MRD-negative patients were enrolled in the study and received transplants with chemotherapy-based conditioning. Participants’ age at the time of their initial B-ALL diagnosis ranged from 2 to 30 with a median age of 13.5 years. Half of the enrolled patients were male. When they received their transplant, half were on their first complete remission after initial treatments and half were on their second complete remission.

To date, participants have been followed for a median of 2.3 years with a range of several months to six years. Researchers compared patients’ outcomes to those of an observational cohort of 151 patients who received the standard TBI conditioning.

At just over two years, 82% of those who received chemotherapy-based conditioning were alive, and 76.3% were alive without experiencing a relapse. Twelve percent of participants died from causes other than a cancer relapse, and 12% experienced a relapse.

Event-free survival and overall survival were similar in the TBI and non-TBI cohorts.

Based on the findings, researchers said that the NGS-MRD test can be a useful biomarker for identifying patients who can safely avoid TBI conditioning. “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) is a common complication of hematopoietic cell transplantation that occurs when transplanted cells attack a patient’s own cells. Ten percent of patients experienced grades 3-4 acute GVHD and 21% experienced chronic GVHD requiring systemic treatment.

Younger age at diagnosis and younger age at the time of hematopoietic cell transplantation were associated with inferior outcomes. Among patients who were NGS-MRD negative, outcomes were similar among those with high-risk and non-high-risk genetic abnormalities.

The researchers plan to further investigate genetic abnormalities and other factors that may influence outcomes in order to guide decisions about which conditioning regimen to recommend based on a patient’s particular risk profile.

The study was funded by the Gateway for Cancer Research.

Hisham Abdel-Azim, MD, of Loma Linda University School of Medicine Cancer Center, will present this study on Saturday, December 6, 2025, at 12:00 noon Eastern time in W331 of the Orange County Convention Center.

###

The American Society of Hematology (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Since 1958, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. Join the #Fight4Hematology by visiting hematology.org/fight4hematology.

The Blood journals (https://ashpublications.org/journals) are the premier source for basic, translational, and clinical hematologic research. The Blood journals publish more peer-reviewed hematology research than any other academic journals worldwide.

END