1.
Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Pediatric Patients With Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation
Sun, S. Y., DeFor, T. E., Ehler, E., Weisdorf, D. J., Macmillan, M., Terezakis, S. A., Dusenbery, K. E.
International journal of radiation oncology, biology, physics. 2021;111(3s):e177-e178
Abstract
PURPOSE/OBJECTIVE(S): To evaluate the relationship between total body irradiation (TBI) and other factors in the development of idiopathic pneumonia syndrome (IPS) in pediatric patients undergoing allogeneic hematopoietic cell transplantation (HCT) for acute leukemia. MATERIALS/METHODS Between 2006-2019, 121 pediatric patients with acute leukemia (84 lymphoblastic, 37 myeloid), ranging in age from 1 to 21 years (median 12), underwent allogeneic HCT at a single institution with matched sibling (n?=?33), single unrelated cord blood (sUCB; n?=?57), or double unrelated cord blood (dUCB; n?=?31) donor. Pretransplantation conditioning included cyclophosphamide (100-120 mg/kg) with (n?=?89) or without fludarabine (75 mg/m(2)) (n?=?32). TBI was delivered in 8 b.i.d. fractions of 1.65 Gy over 4 days via opposed lateral beams of 6, 18, or 25 MV prescribed to midplane at umbilicus, with the patient in a semi-recumbent position, and without lung shielding. Aluminum lung compensator was utilized if predicted mid-lung point dose was =3% higher than prescription dose (n?=?28). Dose rate was specified at 9-20 cGy/min and depended on linear accelerator availability. Patients were stratified by receipt of high-dose-rate (HDR; > 15 cGy/min; 36%) or low-dose-rate (LDR; =15 cGy/min; 64%) delivery. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. The association between treatment factors and IPS was examined. RESULTS Overall, IPS developed in 22 (18%) patients from day 6 to 83 (median 20) after HCT. On univariate analysis, factors associated with IPS included donor type (matched sibling 12%, sUCB 12%, dUCB 35%, P < 0.01), HDR TBI (35% vs 9% for LDR, P < 0.01), and lower beam energy (35% for 6 MV and 15% for 18/25 MV, P?=?0.04). The finding of beam energy significance is likely the result of the 6 MV cohort having a greater dose rate (median 16 cGy/min) than the 18/25 MV cohort (11 cGy/min). On competing risk regression analysis, the pre-specified factors of dose rate, beam energy, lung compensator, age, HCT comorbidity index, and donor type were included in the model. All factors except age (hazard ratio [HR] 1.09, P?=?0.20) and lung compensator (HR 1.8, P?=?0.17) showed an independent statistically significant association with IPS. Kaplan-Meier estimated 1-year survival was 73% for the entire cohort. Time-dependent effect of IPS did not show an association with overall survival (HR 1.2, P?=?0.76). CONCLUSION TBI dose rate is an important variable in the risk of pulmonary toxicity in children treated with allogeneic HCT. TBI dose rates =15 cGy/min reduced the risk of posttransplantation IPS and should be strongly considered as an easily implemented parameter in pre-transplantation TBI-based conditioning.
2.
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.