CORTICOSTEROIDS AS ADJUNCTIVE THERAPY FOR DIFFUSE ALVEOLAR HEMORRHAGEASSOCIATED WITH BONE-MARROW TRANSPLANTATION

Background: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow tran splantation and is associated with very high mortality. This disorder' s association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pu lmonary hemorrhage syndromes provided the rationale for this study. Me thods: We retrospectively studied 65 episodes of diffuse alveolar hemo rrhage that had occurred in 63 of 603 consecutively treated patients w ho had undergone high-dose chemotherapy with bone marrow transplantati on. Patients were divided into three groups according to the therapy t hey had received for diffuse alveolar hemorrhage: supportive therapy a lone in = 12); low-dose corticosteroids (30 mg or less of methylpredni solone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital disch arge, occurrence of respiratory failure requiring intubation, and deve lopment of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. Results: Overall survival at the end of the followup perio d was significantly higher for the high-dose corticosteroid group comp ared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive ther apy alone (P = 0.198). In addition, survival to discharge was signific antly increased for the high-dose group compared with the other two gr oups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of t he 22 unintubated patients in the high-dose group compared with 9 of t he 10 initially unintubated patients in the other two groups (P = 0.05 6). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticoste roid treatment significantly increased the risk of infections (P >0.4, all comparisons). Conclusions: In this study, high-dose corticosteroi d therapy for diffuse alveolar hemorrhage related to bone marrow trans plantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, an d further prospective studies are warranted to verify the effectivenes s of the treatment.