Comparison of Pulmonary Toxicity after Total Body Irradiation- and Busulfan-Based Myeloablative Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients

Pulmonary toxicity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for childhood leukemia and myelodysplastic syndrome (MDS), along with the impact of different myeloablative conditioning regimens, remain incompletely described. Here we compared the acute and long-term incidence of pulmonary toxicity (PT) after total body irradiation (TBI)-and busulfan-based myeloablative conditioning. We conducted this retrospective cohort study of 311 consecutive pediatric patients with leukemia or MDS who underwent allo-HSCT at Dana-Farber Cancer Insti-tute/Boston Children's Hospital between 2008 and 2018. PT was graded using Common Terminology Criteria for Adverse Events version 5.0. The primary objective was to compare the cumulative incidence of grade >= 3 and grade 5 PT after TBI-based and busulfan-based myeloablative conditioning using Gray's test. Secondary objectives were to determine factors associated with PT and overall survival (OS) using competing risk analysis and Cox regression analy-ses, respectively. There was no significant difference between the TBI-conditioned group (n = 227) and the busulfan-conditioned group (n = 84) in the incidence of grade >= 3 PT (29.2% versus 34.7% at 2 years; P = .26) or grade 5 pulmo-nary toxicity (6.2% versus 6.1% at 2 years; P = .47). Age (hazard ratio [HR], 1.70, 95% confidence interval [CI], 1.11 to 2.59; P = .01), grade >= 2 PT prior to allo-HSCT or preexisting pulmonary conditions (HR, 1.84, 95% CI, 1.24 to 2.72; P < .01), acute graft-versus-host disease (GVHD) (HR, 2.50; 95% CI, 1.51 to 4.14; P < .01), and chronic GVHD (HR, 2.61; 95% CI, 1.26 to 5.42; P = .01) were associated with grade >= 3 PT on multivariable analysis. Grade >= 3 PT was associated with worse OS (81.1% versus 61.5% at 2 years; P < .01). In pediatric allo-HSCT recipients, rates of PT were similar in recipients of TBI-based and recipients of busulfan-based myeloablative conditioning regimens. Age, the presence of PT or preexisting pulmonary conditions prior to transplantation, and the development of either acute or chronic GVHD were associated with grade >= 3 PT post-transplantation. Furthermore, the occurrence of grade 3-4 PT post -transplanta-tion was associated with inferior OS. (c) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

This study compared the incidence of pulmonary toxicity (PT) after different myeloablative conditioning regimens in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemia and myelodysplastic syndrome (MDS). The results showed no significant difference in the occurrence of PT between the total body irradiation (TBI)-based and busulfan-based conditioning groups. Age, preexisting pulmonary conditions, acute and chronic graft-versus-host disease (GVHD) were associated with higher-grade PT, and higher-grade PT was associated with worse overall survival (OS).