Long-term complications after total body irradiation in children younger than 4 years transplanted for acute lymphoblastic leukemia.
In a matched observational cohort with mean follow-up of 15.6 years, children receiving TBI-based HSCT for ALL at ages 2 to <4 years did not have a greater overall long-term complication burden, poorer educational outcomes, or worse quality of life than older prepubertal children.
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In a matched observational cohort with mean follow-up of 15.6 years, children receiving TBI-based HSCT for ALL at ages 2 to <4 years did not have a greater overall long-term complication burden, poorer educational outcomes, or worse quality of life than older prepubertal children.
Research significance
The reported human observational evidence suggests that age 2 to <4 years may not independently confer greater long-term toxicity after TBI-based HSCT; it can therefore motivate prospective validation of whether selected younger children could receive TBI-based conditioning, but it does not establish safety, comparative efficacy, or an optimal lower age threshold.
Source abstract
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.