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Influence of total body irradiation dose rate on idiopathic pneumonia syndrome in acute leukemia patients undergoing allogeneic hematopoietic cell transplantation
Gao, R. W., Weisdorf, D. J., DeFor, T. E., Ehler, E., Dusenbery, K. E.
International journal of radiation oncology, biology, physics. 2018
Abstract
PURPOSE/OBJECTIVES To determine the relationship between dose rate and other factors with the development of idiopathic pneumonia syndrome (IPS) in acute lymphoblastic (ALL) and acute myeloid (AML) leukemia patients undergoing total body irradiation (TBI)-based myeloablative conditioning for allogeneic hematopoietic cell transplantation (HCT). MATERIALS/METHODS From 2006 to 2016, 202 acute leukemia patients (111 ALL, 91 AML) ranging in age from 1 to 57 years (median: 25) underwent allogeneic HCT at XXX. Pre-transplantation conditioning included cyclophosphamide (120 mg/kg) with (68%) or without fludarabine (75 mg/m(2)) followed by 13.2 Gy TBI given in 8 twice daily fractions of 1.65 Gy over 4 days. Dose rate varied based on linac availability and ranged from 8.7-19.2 cGy/min. Patients were stratified by receipt of high (>15 cGy/min) (HDR) (56%) or low (≤15 cGy/min) dose rate (LDR) (44%) TBI for all 8 fractions. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, and/or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. RESULTS IPS developed in 42 (21%) patients between 4 and 73 days (median: 16) after transplantation. HDR TBI was associated with a higher rate of IPS compared to LDR TBI [29% versus 10%, P<.01]. On multiple regression analysis, HDR remained a significant predictor of IPS [HR: 2.6 (95% CI: 1.2-5.3), P=.01) and this led to inferior 1-year overall survival (60% versus 76%, P=.01) and increased 1-year non-relapse mortality (28% versus 15%, P=.02). CONCLUSIONS TBI dose rates ≤15 cGy/min reduce the risk of post-transplantation IPS and improve overall survival. LDR TBI should be strongly considered as an easily implemented parameter to improve the safety of pre-transplantation TBI-based conditioning.