Lung damage following bone marrow transplantation: I. The contribution of irradiation

Abstract

High dose whole body irradiation is commonly included in conditioning regimens for bone marrow transplantation for treatment of patients with hematological malignancies. Interstitial pneumonitis is a major complication after BMT. About one-fourth of all BMT patients die from IP. In about half of these cases, an infectious agent, particularly cytomegalovirus, is involved. When no infectious cause is found, it is classified as idiopathic IP (IIP). Total body irradiation is often associated with the induction of IIP; however, extrapolation of animal data from the experiments presented indicates that this is not the only factor contributing to IIP in man. Brown Norway (BN/Bi) rats were bilaterally irradiated to the lungs with 300 kV X rays at a high dose rate (HDR; 0.8 Gy/min) and at a low dose rate (LDR; 0.05 Gy/min). The dose-response curves found were very steep. In the LDR group, lung function studies were performed. There was a strong correlation between the increase in ventilation rate and the death pattern. The LD50 at 180 days was 13.3 Gy for HDR and 22.7 Gy for LDR. The ratios of LD50/180 at 0.05 Gy/min to that at 0.8 Gy/min is 1.7, which indicates a great repair capacity of the lungs. Extrapolation of animal data to patient data leads to an estimated dose of about 15-16 Gy at a 50% radiation pneumonitis induction for low dose rate TBI. As the absorbed dose in the lungs of BMT patients rarely exceeds 10 Gy, additional factors such as remission-induction chemotherapy, cyclophosphamide, methotrexate, cyclosporin A, graft-versus-host disease, etc., might be involved in the high incidence of IIP in man after BMT.