• Ashwin Shinde, Dongyun Yang, Paul Frankel, An Liu, Chunhui Han, Del VecchioBiancaBDepartment of Information Sciences, City of Hope National Medical Center, Duarte, California., Timothy Schultheiss, Jonathan Cheng, Richard Li, Daniel Kim, Eric H Radany, Susanta Hui, George Somlo, Joseph Rosenthal, Anthony Stein, Stephen Forman, and Jeffrey Y C Wong.
• Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.
• Int. J. Radiat. Oncol. Biol. Phys. 2019 Dec 1; 105 (5): 1025-1033.

PurposeToxicities after organ sparing myeloablative total marrow irradiation (TMI) conditioning regimens have not been well characterized. The purpose of this study is to report pulmonary, renal, thyroid, and cataract toxicities from a prospective trial monitoring patients up to 8 years after TMI.Methods And MaterialsA total of 142 patients with primarily multiple myeloma or acute leukemia undergoing hematopoietic cell transplantation were evaluated. Follow-up included pulmonary function tests, serum creatinine, glomerular filtration rate, thyroid panel, and ophthalmologic examinations performed at 100 days, 6 months, and annually. Median TMI dose was 14 Gy (10-19 Gy) delivered at 1.5 to 2.0 Gy twice per day at a dose-rate of 200 cGy/min.ResultsMedian age was 52 years (range 9-70). Median follow-up (range) for all patients was 2 years (0-8) and for patients alive at the time of last follow-up (n = 50), 5.5 years (0-8). Mean organ doses in Gy were lung 7.0, kidneys 7.1, thyroid 6.7, and lens 2.8. The crude incidence of radiation pneumonitis (RP) was 1 of 142 (0.7%). The cumulative incidence of infection and RP (I/RP) was 22.7% at 2 years post-TMI. Mean lung dose ≤8 Gy predicted for significantly lower rates of I/RP (2-year cumulative incidence 20.8% vs 31.8%, P = .012). No radiation-induced renal toxicity was noted. Hypothyroidism occurred in 6.0% and cataract formation in 7.0% of patients.ConclusionsTMI delivered with intensity modulated radiation therapy results in lower organ doses and was associated with fewer toxicities compared with historical cohorts treated with conventional total body irradiation. Keeping the mean lung dose to 8 Gy or less was associated with lower pulmonary complications. Further evaluation in clinical trials of intensity modulated radiation therapy to deliver TMI, total marrow and lymphoid irradiation, and organ sparing conformal total body irradiation is warranted.Copyright © 2019 Elsevier Inc. All rights reserved.

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