title: Diffuse alveolar hemorrhage: retrospective review of clinical outcome in allogeneic transplant recipients treated with aminocaproic acid.
abstract: Diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (HSCT) is often fatal. Standard therapy with high-dose corticosteroid is not always effective. There is paucity of data in the literature about other potentially useful agents, such as aminocaproic acid (Amicar) in the post-transplantation setting. We retrospectively reviewed our data on 115 consecutive patients who underwent HSCT and had pulmonary complications, with the aim of determining the overall clinical outcome in recipients of allogeneic transplants and in the subgroup of these patients who were treated with concomitant Solu-Medrol and aminocaproic acid. Aminocaproic acid was added at the discretion of the attending physician. We identified 14 allogeneic transplant recipients (median age, 41 years) with 15 episodes of DAH who were treated with Solu-Medrol (250 mg to 1 g intravenously per day). Of these, 8 patients also received concomitant aminocaproic acid at 1000 mg intravenously every 6 hours. Failure to improve was the most common reason for adding aminocaproic acid. The incidence of DAH was 12.2% (10.3% in myeloablative versus 1.9% in nonmyeloablative recipients). The overall 100-day DAH mortality and median transplantation survival were 60% and 99 days, respectively. Among the subset of patients treated with the combination of Solu-Medrol and aminocaproic acid, we observed a 100-day DAH mortality and median transplantation survival of 44% and 167 days, respectively, compared with 83% and 96.5 days in those treated with Solu-Medrol alone. The median time to DAH was 40.5 days, and the median time to death was 53 days in the combined treatment group compared with 29.5 days in those treated with steroid alone. There were no significant differences in coagulation parameters between subsets. Infections (yeast, respiratory syncytial virus, herpes simplex virus, and parainfluenza) were isolated and treated from 6 diagnostic bronchial alveolar lavage samples and were more common in the subgroup treated with Solu-Medrol only. Respiratory failure was the documented cause of death in 89% of patients. There were no clinically significant side effects from aminocaproic acid. Although these historically lower DAH outcomes are intriguing, prospective studies are needed to confirm the role of aminocaproic acid in DAH occurring in the allogeneic transplantation setting.
authors.affiliation: Department of Medicine, Division of Cellular Therapy/BMT, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Sam O
authors.initials: SO
authors.lastname: Wanko
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Folz
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
mesh_terms: D000328:Adult; D000614:Aminocaproates / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D012131:Respiratory Insufficiency / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000614:Aminocaproates; D000893:Anti-Inflammatory Agents; D008776:Methylprednisolone Hemisuccinate