Acute Pulmonary Toxicity after Allogeneic Stem Cell Transplantation Using Total Body Irradiation-Based Conditioning- Myeloablative vs. Non-Myeloablative Regimens

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with a high risk of acute pulmonary toxicity, especially with total body irradiation-based (TBI) conditioning regimens. High-grade acute pulmonary toxicity occurs in ∼30% of patients when a myeloablative regimen is utilized (∼12-14 Gy). The risk of pulmonary toxicity with non-myeloablative regimens (∼2 Gy) is not well described. We evaluated the incidence and predictors of acute pulmonary toxicity after HSCT comparing myeloablative and non-myeloablative TBI-based conditioning regimens. All adult (≥ 18 y/o) patients undergoing allogeneic HSCT with TBI (1995-2020) at our institution were evaluated. The dose to the lungs was attenuated to 7-10 Gy in all patients undergoing myeloablative TBI. Acute pulmonary toxicity, occurring within 6 months of HSCT, was scored using CTCAE v5.0. The incidence of acute pulmonary toxicity was calculated using the Kaplan-Meier method, and logistic regression was performed to assess for independent risk factors. Five hundred fifty-two patients were included the analysis (myeloablative- 378; non-myeloablative- 174). Myeloablative TBI was most commonly 13.5 Gy/9Fx (335/378), while non-myeloablative TBI was delivered most often as 2 Gy/1Fx (165/174). Patients undergoing myeloablative TBI were younger than non-myeloablative patients (43 vs 58 years, p<0.001), but baseline pulmonary function parameters were similar. At 6 months after transplant, the cumulative incidences of any acute pulmonary toxicity for patients receiving myeloablative and non-myeloablative TBI were 39% and 33%, respectively (p = 0.11). The risk of low-grade (1-2) and high grade (3-5) pulmonary toxicity was 10% vs 12% (p = 0.59) and 28% vs 21% (p = 0.05), respectively, comparing myeloablative and non-myeloablative TBI. Proportions of high-grade toxicities among the myeloablative and non-myeloablative cohorts were as follows: infectious pneumonia (31% and 49%), bronchopulmonary hemorrhage (25% and 3%), respiratory failure NOS (17% and 10%), pleural effusion (5% and 1%), and pneumonitis (4% and 0%). Female sex (OR 1.52, p = 0.05) and refractory disease at the time of transplant (OR 2.25, p = 0.03) were associated with a higher risk of severe pulmonary toxicity on logistic regression. Younger age (OR 0.99, p = 0.35) and non-myeloablative TBI (OR 0.21, p = 0.60) were not significantly associated with a lower risk. The risk of acute pulmonary toxicity was high with both myeloablative and non-myeloablative TBI-based regimens, though high-grade toxicity was modestly higher in the myeloablative cohort. A better understanding of pulmonary toxicity in the setting of non-myeloablative TBI (∼2 Gy) is needed.