Long-Term Morbidity of Children Receiving Hematopoietic Stem Cell Transplant with Total Body Irradiation Conditioning for Hematologic Malignancies

Objectives To evaluate the prevalence and effect of radiotherapy dose on long-term sequelae experienced by pediatric patients undergoing total body irradiation (TBI) as part of hematopoietic stem cell transplant (HSCT) conditioning for a hematologic malignancy. Methods Pediatric patients whose HSCT conditioning included TBI between 2002 and 2016 were identified in the Childhood Cancer Survivor Cohort. Those who succumbed to their hematologic malignancy were excluded. Sequelae were determined through review of patient charts, practitioner claims, discharge abstracts, and the National Ambulatory Care Reporting System. Fisher's exact test was used to assess the association between TBI dose and long-term sequelae. Results Fifty patients (58% male) with a median age of 9 years at the time of TBI were included. TBI was 4 Gy in 2 twice daily fractions for 64% of patients, 12 Gy in 6 twice daily fractions for 34% of patients, and 3 Gy in 1 fraction for 2% of patients. Cranial irradiation was given to 16% of patients (6-18 Gy in 3-10 fractions) and craniospinal irradiation was given to 10% of patients (7.5-20 Gy in 4-10 fractions). Median follow-up was 10.3 years, over which there were a median of 59 post-HSCT outpatient assessments, 3.5 emergency room visits, and 2 admissions. During follow-up, 34% developed cataracts, 20% hearing loss, 38% hypothyroidism, 58% other endocrinopathies, 18% short stature, 30% developmental or intellectual disabilities, and 72% received a psychiatric diagnosis. Four second primary malignancies were diagnosed in 3 (6%) patients. TBI dose (12 Gy vs. ≤4 Gy) was associated with increased cataracts (65% vs. 18%; P=0.002), short stature (35% vs. 9%; P=0.05), and second primary malignancies (18% vs. 0%; P=0.03). Conclusion Pediatric patients experience a myriad of late toxicities following TBI-conditioned HSCT which may be partially mitigated by doses ≤4 Gy, but further studies are required.