Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Abstract

To determine the relationship between dose rate and other factors in the development of idiopathic pneumonia syndrome (IPS) in patients with acute lymphoblastic leukemia or acute myeloid leukemia who are undergoing total body irradiation (TBI)-based myeloablative conditioning for allogeneic hematopoietic cell transplantation (HCT). From 2006 to 2016, 202 patients with acute leukemia (111 acute lymphoblastic leukemia, 91 acute myeloid leukemia) ranging in age from 1 to 57years (median, 25years) underwent allogeneic HCT at University of Minnesota. Pretransplantation conditioning included cyclophosphamide (120mg/kg) with (68%) or without fludarabine (75mg/m2) followed by 13.2Gy TBI given in 8 twice-daily fractions of 1.65Gy over 4days. Dose rate varied based on linear accelerator availability and ranged from 8.7 to 19.2cGy/min. Patients were stratified by receipt of high-dose-rate (HDR; >15cGy/min; 56%) or low-dose-rate (LDR; ≤15cGy/min; 44%) TBI for all 8 fractions. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100days of HCT in the absence of concurrent infection. IPS developed in 42 patients (21%) between 4 and 73days (median, 16days) after transplantation. HDR TBI was associated with a higher rate of IPS compared with LDR TBI (29% vs 10%; P<.01). On multiple regression analysis, HDR remained a significant predictor of IPS (hazard ratio, 2.6; 95% confidence interval, 1.2-5.3; P=.01), and this led to inferior 1-year overall survival (60% vs 76%; P=.01) and increased 1-year nonrelapse mortality (28% vs 15%; P=.02). TBI dose rates ≤15cGy/min reduce the risk of posttransplantation IPS and improve overall survival. LDR TBI should be strongly considered as an easily implemented parameter to improve the safety of pretransplantation TBI-based conditioning.