Abstract
IntroductionTotal body irradiation is an effective conditioning regimen for allogeneic stem cell transplantation in pediatric and adult patients with high risk or relapsed/refractory leukemia. The most common adverse effect is pulmonary toxicity including idiopathic pneumonia syndrome (IPS). As centers adopt more advanced treatment planning techniques for TBI, total marrow irradiation (TMI), or total marrow and lymphoid irradiation (TMLI) there is a greater need to understand treatment-related risks for IPS for patients treated with conventional TBI. However, definitions of IPS as well as risk factors for IPS remain poorly characterized. In this study, we perform a critical review to further evaluate the literature describing pulmonary outcomes after TBI.Materials and MethodsA search of publications from 1960-2020 was undertaken in PubMed, Embase, and Cochrane Library. Search terms included “total body irradiation”, “whole body radiation”, “radiation pneumonias”, “interstitial pneumonia”, and “bone marrow transplantation”. Demographic and treatment-related data was abstracted and evidence quality supporting risk factors for pulmonary toxicity was evaluated.ResultsOf an initial 119,686 publications, 118 met inclusion criteria. Forty-six (39%) studies included a definition for pulmonary toxicity. A grading scale was provided in 20 studies (17%). In 42% of studies the lungs were shielded to a set mean dose of 800cGy. Fourteen (12%) reported toxicity outcomes by patient age. Reported pulmonary toxicity ranged from 0-71% of patients treated with TBI, and IPS ranged from 1-60%. The most common risk factors for IPS were receipt of a TBI containing regimen, increasing dose rate, and lack of pulmonary shielding. Four studies found an increasing risk of pulmonary toxicity with increasing age.ConclusionsDefinitions of IPS as well as demographic and treatment-related risk factors remain poorly characterized in the literature. We recommend routine adoption of the diagnostic workup and the definition of IPS proposed by the American Thoracic Society. Additional study is required to determine differences in clinical and treatment-related risk between pediatric and adult patients. Further study using 3D treatment planning is warranted to enhance dosimetric precision and correlation of dose volume histograms with toxicities.
Highlights
Total body irradiation is an effective conditioning regimen for allogeneic stem cell transplantation in pediatric and adult patients with high risk or relapsed/refractory leukemia
Allogeneic stem cell transplant is used in a subset of patients with high risk or relapsed/refractory disease
In this report, we critically evaluate the literature with the goal of characterizing the workup and definitions of pulmonary toxicity as well as levels of evidence in support of risk factors for idiopathic pneumonia syndrome (IPS) following total body irradiation (TBI)-based myeloablative stem cell transplant
Summary
Total body irradiation is an effective conditioning regimen for allogeneic stem cell transplantation in pediatric and adult patients with high risk or relapsed/refractory leukemia. Allogeneic stem cell transplant is used in a subset of patients with high risk or relapsed/refractory disease. In pediatric patients with ALL, myeloablative regimens containing total body irradiation (TBI) have demonstrated improvement in event free survival from 29-35% without TBI as compared to 50-58% with and remain the standard of care [3,4,5]. Myeloablative regimens have demonstrated improvements in recurrence free survival at the cost of increased transplant related mortality compared to reduced intensity conditioning regimens [6, 7]. The use of reduced-intensity conditioning regimens has increased over the last decade, in patients 50 years of age and older [8]
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