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.