Late effects following HSCT childhood ALL: a national single center study using 3 different modalities of delivery of total body irradiation

Abstract

Background: Total body irradiation (TBI) is a pivotal part of conditioning prior to hematopoietic stem cell transplantation (HSCT) for childhood acute lymphoblastic leukemia (ALL), yet evidence regarding the effect of TBI delivery techniques on acute and late toxicities is sparse. Design: In a national cohort of pediatric HSCT-recipients we compared 3 TBI schedules from different time-periods: (1) TBI 12 Gray (Gy) delivered in 3 fractions from 2008-2011 (n=12), (2) 6 fractions with 2-dimensional (2D) planning technology from 2012- 2015 (n=16) and (3) 6 fractions with 3D-planning intensity-modulated radiotherapy (IMRT) from 2016-2020 (n=14). Results: The 5-year event-free survival was 75.0%, 81.3% and 81.3% in cohorts 1,2 and 3, respectively. Acute toxicity assessed as maximum ferritin and C-reactive protein during the first 3 months post-HSCT did not differ between cohorts, nor did the time to first hospital discharge (median 28, 32 and 31 days, p=0.25). The incidences of acute graft-versus-host disease (GvHD) (66%, 56%, 71%) and chronic GvHD (25%, 31% and 14%) were comparable. Pulmonary function assessed by spirometry did not differ significantly. More patients in cohort 1 developed cataract, with a 5-year cataract-free survival of 33.3%, 79% and 100% in cohorts 1,2 and 3, respectively. There was a non-significant tendency towards more endocrinopathies in cohort 1 compared to cohorts 2 and 3. Conclusion: The change of modality did not result in more relapses. More fractionation improved outcome with a lower incidence of cataract and a tendency towards fewer endocrinopathies. The effect of 3D-planning-IMRT technology requires further evaluation in larger studies.