Outcomes of High Dose Steroid Treatment with or without Aminocaproic Acid in Critically Ill Stem Cell Transplant Recipients with Diffuse Alveolar Hemorrhage

Diffuse alveolar hemorrhage (DAH) complicates Hematopoietic Stem Cell Transplantation (HSCT) at a rate of 2–14%, and carries a mortality of 70 to 100%. For transplant patients that require intensive care unit (ICU) admission, the prevalence of DAH may be as high as 40%. Patients present with diffuse alveolar infiltrates with or without hemoptysis, and are diagnosed based on bronchoscopic and clinical findings. Retrospective studies have shown that high dose steroid therapy may improve outcomes and has thus been the traditional modality of treatment. A recent small retrospective study, however, cited improved mortality using high dose intravenous methylprednisolone (MP) combined with the anti-fibrinolytic agent aminocaproic acid (ACA) (Wanko et al. Biol Blood Marrow Transplant 2006.12: 949–953). We performed a larger study on the use of ACA and MP versus MP alone to evaluate outcomes on survival.

We retrospectively analyzed all HSCT patients greater than 18 years of age admitted to the ICU that were diagnosed with DAH and treated with either high dose MP and ACA, or high dose MP alone in a consecutive 13 month period. Diagnosis of DAH was based on available bronchoscopic findings showing progressively bloody fluid and hemosiderin-laden macrophages, or a clinical presentation consistent with DAH. Mortality was measured from the time of DAH diagnosis to the time of death.

A total of 28 HSCT patients were included in the analysis. Of the transplants, 24 were allogeneic and 4 were autologous. The median patient age was 51 years, and the cancer categories included acute myelogenous leukemia (n=13), acute lymphoblastic leukemia (n=4), chronic myeloid leukemia (n=2), chronic lymphocytic leukemia (n=1), multiple myeloma (n=5), and lymphoma (2 Non-Hodgkins, 1 Hodgkins). Eleven of the transplants were from related donors, 14 were unrelated, and two were cord blood. Thirty-six percent of the patients were diagnosed with DAH within 30 days of transplantation, with a mean of 245 days post-transplant amongst the entire group. Overall, 82% of the patients required intubation and mechanical ventilation with an average of 14 ventilator days. A total of 57% (n=16) received high dose MP along with continuous ACA (4 gms IV load, followed by 1 gm/hr) vs. 43% (n=12) who received high dose MP alone. ICU severity of illness scores, coagulation parameters, and duration of steroid treatment were equivalent between the two groups. The incidence of GVHD was equivalent (25%) in each group, and there were no differences in mean absolute neutrophil count (5.6 +/− 4.8 vs. 4.2 +/−4.6, p=0.44) or mean platelet count (53.3 +/− 45.3 vs. 48.3 +/− 68.9, p=0.41) on ICU admission in the MP with ACA vs. MP groups respectively. The group receiving MP alone received a lower average daily dose of steroids (mean 300 mg/day, range 80–1000) as compared to the group receiving MP and ACA (mean 560 mg/day, range 100–1000) (p=0.03). There were no differences in 30, 60, 100 day mortality or overall survival between the two groups, with a 100-day mortality of 94% in the ACA with MP group vs. 92% in the MP alone group. The overall mortality was 100% in the ACA with MP group, and 92% in the MP alone group (p=0.68). Additionally, the average number of ventilator days, ICU length of stay (LOS), and hospital LOS did not differ between the two groups. There was no increase in thrombotic events including deep vein thrombosis, myocardial infarction, and ischemic stroke associated with ACA treatment.

Combination therapy with high dose methylprednisolone and aminocaproic acid versus high dose methylprednisolone alone did not improve survival, decrease ventilator days, ICU length of stay or hospital length of stay in critically ill transplant patients with diffuse alveolar hemorrhage.

Popat:Otsuka: Research Funding.