Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group.
BACKGROUND
Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation 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 pulmonary hemorrhage syndromes provided the rationale for this study.


METHODS
We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that has occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone 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 discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage.


RESULTS
Overall survival at the end of the follow-up period was significantly higher for the high-dose corticosteroid group compared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive therapy alone (P = 0.198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups (P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections (P > 0.4, all comparisons).


CONCLUSIONS
In this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation 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, and further prospective studies are warranted to verify the effectiveness of the treatment.
Metcalf
J P
JP
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-2465.
Rennard
S I
SI
Reed
E C
EC
Haire
W D
WD
Sisson
J H
JH
Walter
T
T
Robbins
R A
RA
D000328:Adult; D000704:Analysis of Variance; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid; D002423:Cause of Death; D005260:Female; D006098:Granulocytes; D006470:Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007902:Length of Stay; D007958:Leukocyte Count; D008171:Lung Diseases / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D011650:Pulmonary Alveoli; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D008775:Methylprednisolone