1.
Comparison of pulmonary toxicity after total body irradiation- and busulfan-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation for pediatric patients
Liu, K. X., Poux, N., Shin, K. Y., Moore, N., Chen, Y. H., Margossian, S., Whangbo, J. S., Duncan, C. N., Lehmann, L. E., Marcus, K. J.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Pulmonary toxicity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for childhood leukemia and myelodysplastic syndrome (MDS) and the impact of different myeloablative conditioning remains incompletely described. OBJECTIVE To compare the acute and long-term incidence of pulmonary toxicity after total body irradiation (TBI)- and busulfan-based myeloablative conditioning. STUDY DESIGN We conducted a retrospective cohort study of 311 consecutive pediatric patients with leukemia or MDS who underwent allo-HSCT at Dana Farber Cancer Institute/Boston Children's Hospital between 2008-2018. Pulmonary toxicity was graded using Common Terminology Criteria for Adverse Events v5.0. The primary objective was to compare cumulative incidence of grade ≥3 and grade 5 pulmonary toxicity after TBI- and busulfan-based myeloablative conditioning using Gray's test. Secondary objectives were to determine factors that associate with pulmonary toxicity and overall survival using competing risk analysis and Cox regression analyses, respectively. RESULTS Incidence of grade ≥3 pulmonary toxicity (29.2% vs. 34.7% at 2 years, p=0.26) or grade 5 pulmonary toxicity (6.2% vs. 6.1% at 2 years, p=0.47) did not differ between TBI (n=227) and busulfan (n=84) groups, respectively. Age (Hazard Ratio [HR]: 1.70, 95% Confidence Interval [CI]: 1.11-2.59, p= 0.01), grade ≥2 pulmonary toxicity prior to allo-HSCT or pre-existing pulmonary conditions (HR: 1.84, 95% CI: 1.24-2.72, p<0.01), acute graft versus host disease (GVHD) (HR: 2.50, 95% CI: 1.51-4.14, p<0.01), and chronic GVHD (HR: 2.61, 95% CI: 1.26-5.42, p=0.01) were associated with grade ≥3 pulmonary toxicity on multivariable analysis. Grade ≥3 pulmonary toxicity was associated with worse overall survival (81.1% vs. 61.5% at 2 years; p<0.01). CONCLUSION In pediatric allogeneic transplant recipients, rates of pulmonary toxicity were similar between TBI-based and busulfan-based myeloablative regimen. Age, the presence of pulmonary toxicity or pre-existing pulmonary conditions prior to transplant, and the development of either acute or chronic GVHD were associated with grade ≥3 pulmonary toxicity post-transplant. Furthermore, the occurrence of grade 3-4 pulmonary toxicity post-transplant was associated with inferior overall survival.
2.
Myeloablative TBI is associated with increased risk of pulmonary GVHD in patients undergoing allogeneic hematopoietic stem cell transplant
Baranwal, A., Byun, J., Ritz, E., Kadanagowd, A., Murphy, D., Marinovic, D. A., Wang, D., Okwuosa, T., Katz, D., Varma, A., et al
Bone marrow transplantation. 2022
3.
Pulmonary Toxicity after Total Body Irradiation-An Underrated Complication? Estimation of Risk via Normal Tissue Complication Probability Calculations and Correlation with Clinical Data
Oertel, M., Kittel, C., Martel, J., Mikesch, J. H., Glashoerster, M., Stelljes, M., Eich, H. T.
Cancers. 2021;13(12)
Abstract
Total body irradiation (TBI) is an essential part of various conditioning regimens prior to allogeneic stem cell transplantation, but is accompanied by relevant (long-term) toxicities. In the lungs, a complex mechanism induces initial inflammation (pneumonitis) followed by chronic fibrosis. The hereby presented analysis investigates the occurrence of pulmonary toxicity in a large patient collective and correlates it with data derived from normal tissue complication probability (NTCP) calculations. The clinical data of 335 hemato-oncological patients undergoing TBI were analyzed with a follow-up of 85 months. Overall, 24.8% of all patients displayed lung toxicities, predominantly pneumonia and pulmonary obstructions (13.4% and 6.0%, respectively). NTCP calculations estimated median risks to be 20.3%, 0.6% and 20.4% for overall pneumonitis (both radiological and clinical), symptomatic pneumonitis and lung fibrosis, respectively. These numbers are consistent with real-world data from the literature and further specify radiological and clinical apparent toxicity rates. Overall, the estimated risk for clinical apparent pneumonitis is very low, corresponding to the probability of non-infectious acute respiratory distress syndrome, although the underlying pathophysiology is not identical. Radiological pneumonitis and lung fibrosis are expected to be more common but require a more precise documentation by the transplantation team, radiologists and radiation oncologists.