ORIGINAL ARTICLE Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage NK Rathi 1 , AR Tanner 2 , A Dinh 1 , W Dong 3 , L Feng 3 , J Ensor 3 , SK Wallace 4 , SA Haque 1 , G Rondon 5 , KJ Price 1 , U Popat 5 and JL Nates 1 Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n = 119) on day 100 was high at 85%. In the steroids and ACA cohort (n = 82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n = 37), the low-dose steroid group had a lower ICU and hospital mortality (P = 0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P = 0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies. Bone Marrow Transplantation (2015) 50, 420–426; doi:10.1038/bmt.2014.287; published online 22 December 2014 INTRODUCTION Pulmonary complications occur in up to 60% of hematopoietic SCT (HSCT) recipients and are a leading cause of morbidity and mortality. 1–4 Diffuse alveolar hemorrhage (DAH) is a syndrome consisting of hypoxia, multilobar pulmonary infiltrates and progressively bloody bronchoalveolar lavage (BAL) fluid. 5 It has been reported to affect ~ 5–12% of HSCT patients yearly; however, more recent studies indicate the incidence to be closer to 5%. 6–8 BAL fluid, however, lacks sensitivity and specificity when compared with autopsy findings, which hinders early and accurate diagnoses. 9 Despite prompt therapy and supportive care, the mortality rate for DAH remains high at 60–100%. Patients commonly require intensive care unit (ICU) admission and invasive mechanical ventilation; therefore, there is an imminent need to better clarify optimal treatment strategies. All previous studies to date specifically on DAH have been retrospective in nature. High-dose steroids have historically been suggested as the primary therapy for noninfectious DAH to neutralize the inflammatory insult theorized to be an underlying cause of hemorrhage. 8,10–15 Post-HSCT DAH patients have an increased number of bronchial neutrophils and eosinophils on pre-transplant bronchoscopy as compared with their counterparts without DAH. 16 The unwanted side effects, however, such as myopathy, glucose intolerance, psychiatric disturbances and an increased susceptibility of infections mandate the judicious use of steroids. 17–20 Furthermore, treatment strategies vary widely in many transplant centers 10,11 and the benefit of high-dose steroids in critically ill DAH patients remains undefined. Adjunctive therapies such as the antifibrinolytic agent aminocaproic acid (ACA) have also been proposed, 15 and over 60% of ICU patients with DAH in our institution receive intravenous ACA despite the uncertain efficacy. The limitation in available data, persistently poor outcomes and ambiguity surrounding optimal treatment prompted our institu- tion to analyze critically ill post-HSCT patients receiving various therapies for DAH. We describe the characteristics of critically ill patients with alveolar hemorrhage at a large HSCT center, and evaluate the differences in mortality when patients are treated with varying doses of steroids with or without ACA. MATERIALS AND METHODS The study was approved by The University of Texas MD Anderson Cancer Center Institutional Review Board before initiation. All consecutive adult patients admitted to the ICU between October 2007 and June 2011 who received intravenous steroid therapy on or after ICU admission were retrospectively screened via manual chart review. HSCT recipients who received steroid therapy ± ACA for DAH treatment were included. Exclusion criteria included age o18, or steroids ± ACA administration for non-DAH illnesses. Patients were initially stratified based on treatment with (A) steroids only or (B) steroids with ACA. Within each group, patients were categorized based on the initial dose of methylprednisolone: (1) low dose: o250 mg/day, (2) medium dose: 250–1000 mg/day and (3) high dose: ⩾ 1000 mg/day. Dosing for the first 5 days of therapy was measured. Steroid dose, tapering strategies and ACA treatment were determined by the oncologists and/or ICU-attending physicians. Diagnostic methods 1 Department of Critical Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2 Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4 Department of Clinical Analytics and Informatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA and 5 Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Correspondence: Dr NK Rathi, Department of Critical Care, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 112, Houston, TX 77030, USA. E-mail: nrathi@mdanderson.org Received 23 July 2014; revised 31 October 2014; accepted 7 November 2014; published online 22 December 2014 Bone Marrow Transplantation (2015) 50, 420 – 426 © 2015 Macmillan Publishers Limited All rights reserved 0268-3369/15 www.nature.com/bmt