Long-term complications after total body irradiation in children younger than 4 years transplanted for acute lymphoblastic leukemia.

Total body irradiation (TBI)-based conditioning is the standard regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in high-risk or relapsed pediatric acute lymphoblastic leukemia (ALL), but is variably used before age 4 because of concerns about long-term toxicity. Long-term physical, educational, and quality-of-life outcomes were assessed in patients from the French long-term follow-up program LEA who underwent TBI-based HSCT for ALL at 2 to <4 years of age (younger group, n = 37) and compared with those of matched prepubertal older children transplanted at ≥4 years (older group, n = 105). After a mean follow-up of 15.6 years, the number of complications was similar in the two groups (3.3 vs 3.2, p = 0.90). Among the 20 complications analyzed, pulmonary dysfunction was the only event that differed significantly, being more frequent in the older group (43% vs 19%, p = 0.01). In a multivariate multistate model, age group was not associated with a higher risk of transition to a greater complication burden (HR 1.05, 95% CI 0.83-1.32; p = 0.70). Educational outcomes and quality of life were also comparable. These findings do not suggest greater long-term toxicity in children undergoing TBI-based HSCT at 2 to <4 years of age and support reconsideration of the lower age limit for its use.