Adverse Effects of Total Body Irradiation: A Single Institution Analysis

Abstract

Total body irradiation (TBI) is commonly used as part of the conditioning regimen prior to stem cell transplant. While TBI may be valuable in this setting, several potential adverse effects have been reported in the literature. Data describing adverse effects of TBI have been primarily drawn from single institution retrospective analyses. We report one of the largest cohorts of TBI patients treated using multiple preparative chemotherapy and radiation regimens. The purpose of our study was to evaluate the potential acute, subacute, and late adverse treatment related toxicities. A retrospective chart review was performed on a cohort of 705 patients treated at our institution from 1995-2017. Based on availability of TBI records, 624 patients had evaluable documentation for analysis. Patients received one of four conditioning regimens including busulfan-fludarabine-2Gy TBI, fludarabine-melphalan-2Gy TBI, cyclophosphamide-12Gy fractionated TBI, and etoposide-12Gy fractionated TBI. Individual patients were evaluated for 13 specific CTCAE recognized adverse effects (dermatitis, alopecia, febrile neutropenia, lung infection, pneumonitis, oral mucositis, nausea, diarrhea, ARDS, cataracts, non-infective cystitis, secondary malignancy, and pulmonary fibrosis) and were graded based on CTCAE version 5.0. Overall median follow-up time was 59 months (95% CI 51, 62), and median survival was 42 months (95% CI 32, 59). The etoposide-12 Gy regimen showed a significantly higher mucositis rate compared to the other regimens, especially grade 3 mucositis (39.6%, p< 0.001). Otherwise, there were no significant differences in toxicity by regimen for the 13 adverse effects reviewed. The overall rate of secondary malignancy was low (n=1, 0.2%). Cataract formation occurred in 16.2% of patients without a significant difference between regimens (p = 0.32). Median time to cataract formation was relatively short, ranging from 1-4 years. There was no difference in pneumonitis rate among the four different regimens; however, the overall grade 3 or higher pneumonitis rate was relatively low (n=11, 1.8%, p = 0.15). TBI regimens delivered at our facility ranging from a single fraction of 2 Gy to fractionated 12 Gy regimens showed relatively low rates of radiation related toxicities. However, cataracts were a common toxicity with a relatively short onset time. Interestingly, cataract formation did not appear to be dose-dependent. Improved knowledge of the potential sequelae of TBI may prove beneficial for the initial counseling and long-term care of stem cell transplant patients.