Adverse Effects of Total Body Irradiation: A Two-Decade, Single Institution Analysis

Abstract

Purpose: Several adverse effects have been reported in the literature associated with total body irradiation (TBI). Reports of the adverse effects of TBI have been primarily drawn from single-institution retrospective analyses. We report, to our knowledge, one of the largest cohorts of patients treated with TBI using multiple preparative chemotherapy and radiation regimens. Methods and Materials: A retrospective chart review was performed for all 705 patients treated with TBI at our institution from 1995 to 2017. Based on availability of TBI records, 622 patients (88%) had sufficient evaluable documentation for analysis. Patients received 1 of 4 conditioning regimens: busulfan-fludarabine, 2 Gy (BUFLU); fludarabine-melphalan, 2 Gy (FLUMEL); cyclophosphamide, 12 Gy fractionated (CY); or etoposide, 12 Gy fractionated (VP16). Individual patients were evaluated for 13 specific recognized adverse effects based on the Common Terminology Criteria for Adverse Events, version 5.0. Results: Mucositis (grade 3) was the most common serious adverse effect and occurred most frequently in the group receiving the VP16 12 Gy regimen (40% vs less than 14% in each of the other groups). Serious febrile neutropenia (grade 3-5) was less frequent (24%) among patients receiving CY than among those receiving the other conditioning regimens (more than 38% in each of the other groups). The incidence of serious lung infection was less common (5%) in patients receiving CY than in those receiving VP16 (18%). There was a higher frequency of grade 3-5 diarrhea among those receiving FLUMEL (5%) and VP16 (4%) than in the other groups (<3%) (P = .034). Otherwise, there were no detectable differences in serious toxicity by regimen for the 13 adverse effects reviewed. Only 2 secondary malignancies were reported, and both were in the BUFLU group. Cataract formation occurred in approximately 16% of patients overall, and the rates were similar across regimens. Median time to cataract formation was 1 to 4 years across regimens, with cataracts occurring earlier in the 2-Gy regimens. The overall rate of grade ≥3 pneumonitis was approximately 2% across the entire cohort. Conclusions: Our nearly 20-year TBI experience showed relatively low rates of radiation-related toxicities. However, cataracts were common with a relatively short onset time.