Association between Lung Dose and Incidence of Pulmonary Toxicity after Total Body Irradiation Open Access

Yu, Mengda (Spring 2020)

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Background: Previous studies regarding the effect of total body irradiation (TBI) on pulmonary injury is continuously disputed. Our study was designed to examine factors related to exaggerated risk of pulmonary toxicity (PT) among pediatric patients when myeloablative conditioning is performed by TBI followed with allogeneic hematopoietic stem cell transplantation (HSCT). We tried to find an undeniable association between incidence of PT and higher total body irradiation dose rate within the setting of comparatively homogenized TBI techniques.

Methods and Materials: Medical data of 148 pediatric patients that received TBI-based myeloablative conditioning in a single institution from 2003 to 2018 have been reviewed. Pulmonary toxicity was identified by development of clinical symptoms, radiographic evidence, or ventilatory defects on pulmonary function tests. We used univariate association analysis to compare incidence of infectious pneumonitis and non-infectious. Multivariable analysis of pulmonary toxicity was done by involving covariates in the logistic regression model. Differences in relapse-free survival and overall survival were examined by Kaplan-Meier method and log-rank test.

Results: Patients were divided into two groups: >8Gy lung dose group and 8Gy lung dose group. 111 patients out of ???119 (93.28%) developed pneumonitis in the >8Gy lung dose group, and 11 patients out of ???29 (37.93%) developed pneumonitis in the 8Gy group. We found that pneumonitis toxicity is strongly related to lung dose limit (infectious pneumonitis: p<0.001 and non-infectious pneumonitis: p=0.046). The odds ratio for relapse rate with a lung dose limit of 8Gy compared to >8Gy is 0.426 (p<0.029). Pulmonary toxicity developed in 85.0% of patients with higher GVHD grade (p=0.001). TBI dose rate is a significant factor associated with PT (p=0.002). PT is 5.33 times more likely to occur in pediatric patients undergoing higher than 15Gy/min than patients treated with dose rates of 5-10Gy/min (p=0.018).

Conclusions: Within this cohort of homogeneously treated pediatric patients receiving TBI for allogeneic HSCT, we found a large incidence of pulmonic toxicity. The existence of high grade (III and IV) GVHD and infection were the foremost important factor tributary to pulmonic toxicity. To reduce the danger of pulmonic toxicity, TBI rate ought to be controlled below 15cGy/min. Reducing lung dose constraint has a positive impact on decreasing incidence of pneumonitis. And this procedure is not a risk towards overall survival.

Table of Contents


Introduction. 1

Methods and Materials. 3

Study Population. 3

Bone marrow transplant procedure. 3

Evaluation of PT and Other Clinical Outcomes. 4

Descriptive analysis. 5

Statistical Analysis. 5

Results. 6

Differences between lung dose limit of 8Gy and >8Gy. 7

Effects of CR status and MRD status. 7

Effects of GVHD.. 8

Effects of TBI total dose, TBI dose per fraction, TBI dose rate, lung thickness. 9

Effects of age, gender, donor type and engraftment 9

Discussion. 9

References. 13

Appendix. 15


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