1. Results Conclusion Disclosures LimitationsMethods Purpose Background Etanercept for the treatment of pulmonary complications after hematopoietic stem cell transplantation Jeremy R. DeGrado PharmD BCPS 1, Kelly Babcock PharmD Candidate 2, Kevin E. Anger PharmD BCPS 1, Paul M. Szumita PharmD BCPS 1 1 Department of Pharmacy Brigham and Womens Hospital, Boston, MA 2 Northeastern University, Boston, MA Hematopoietic stem cell transplantation (HSCT) is an important therapy in the treatment of both malignant and non- malignant disorders Pulmonary complications following HSCT include various noninfectious conditions, such as idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), and cryptogenic organizing pneumonia (COP) The exact pathogenesis of many of these pulmonary complications is unknown, but may involve immunologic factors and cytokines, such as tumor necrosis factor-α 1 Pulmonary dysfunction occurs in up to 55% of transplant recipients and mortality remains high, ranging between 50 to 90% 1,2 Treatment often involves mechanical ventilation and high dose corticosteroids, although their efficacy has not been established 3 The use of etanercept in addition to corticosteroids has been encouraging in some smaller studies, but prospective studies are lacking 2,4 To evaluate the safety of etanercept in patients with pulmonary complications following HSCT The authors of this presentation have no disclosures concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation References Both hospital and long-term mortality were high and consistent with previous studies The incidence and severity of suspected adverse drug events following the initiation of etanercept is noteworthy Prospective, randomized data are needed to weigh the risks of etanercept against the possible benefits in patients with pulmonary complications following HSCT Single center, retrospective analysis Incomplete data to determine effects on pulmonary parameters Small sample size 1.Yen KT, Lee KS, Krowka MJ, Burger CD. Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment. Clin Chest Med. 2004;25:189-201 2.Yanik GA, Ho VT, Levine JE, et al. The impact of soluble tumor necrosis factor receptor etanercept on the treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Blood. 2008;112:3073-3081 3.Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest. 2010;137:1164-71 4.Yanik G, Hellerstedt B, Custer J, et al. Etanercept (Enbrel) administration for idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2002;8:395-400 Single center, retrospective cohort analysis at a tertiary academic medical center Approval obtained from institutional review board A hospital database was used to identify all adult patients who received etanercept from 2005 to 2010 Patient Enrollment 353 HARVARD MEDICAL SCHOOL TEACHING AFFILIATE 83 patients ordered for etanercept 17 patients included 66 cases excluded 62 had other indication 3 never received 1 enrolled in other etanercept study Outcomes assessed included baseline demographics, number of infections, type of infections, adverse drug events, ICU and hospital lengths of stay, and survival Diagnosis of infection required both documentation of proven or suspected infection as well as a positive culture, viral load, or fungal marker Inclusion criteria: Age 18 Suspected pulmonary complication s/p HSCT Included IPS, DAH, or COP Exclusion criteria: Etanercept for any other indication Patient involvement in any other study Baseline Characteristics Variable Patients (n = 17) Age, years*42.9 ± 12.2 Male 13 (76) Height, inches*68.4 ± 4.4 Actual Body Weight, kg*81.9 ± 18.6 Ideal Body Weight, kg*67.8 ± 11.7 BMI, kg/m 2 *27.1 ± 5.1 APACHE II* α 22.3 ± 8.9 Serum creatinine, mg/dL*1.2 ± 0.9 WBC, 10 3 /µL*8.7 ± 6.2 Platelets, 10 3 /µL*95.5 ± 82.6 Tbili, mg/dL*1.8 ± 2.5 PaO2/FiO2*96.7 ± 39.8 Mechanical ventilation 14 (82.3) Pulmonary complication IPS10 (58.9) DAH5 (29.4) COP2 (11.7) Hematologic diagnosis AML7 (53.8) MDS3 (17.6) ALL2 (11.8) Hodgkins lymphoma2 (11.8) Other β 3 (17.6) Donor type URD11 (64.7) MRD5 (29.4) Autologous1 (5.9) Medications Tacrolimus11 (64.7) Sirolimus7 (53.8) Mycophenolate10 (58.9) Cyclosporine2 (11.8) Steroids16 (94.1) Vasoactive agents10 (58.9) * Mean ± SD; n (%); α n=13 patients; β progressive multifocal leukencephelopathy (n=1), common variable immunodeficiency (n=1), polycythemia vera (n=1) IPS = idiopathic pneumonia syndrome; DAH = diffuse alveolar hemorrhage; COP = cryptogenic organizing pneumonia; AML = acute myeloid leukemia; MDS = myelodysplastic syndrome; ALL = acute lymphoblastic leukemia; URD = unrelated donor; MRD = matched related donor Drug Treatment Characteristics Patients (n = 17) Initiated etanercept in ICU 13 (76.4) Time from HSCT to etanercept, days * 249 ± 196 Number of doses * 3.4 ± 2.4 * Mean ± SD; n (%) Results Suspected Adverse Drug Events Patients (n = 17) Patients with documented infection 4 (23.6) Total number of infections5 Pathogen isolated Fungal2 Bacterial2 Viral1 Time from etanercept initiation to infection, days*23.8 ± 13.3 Patients with skin reaction 2 (11.7) TEN1 Rash1 Mean ± SD; n (%) TEN = Toxic Epidermal Necrosis Patient Outcomes Patients (n = 17) ICU length of stay, days*21 ± 20 Hospital length of stay, days*37 ± 24 ICU survival 4 (23.5) Hospital survival 4 (23.5) Survival at 100 days 3 (17.6) Survival at 1 year 3 (17.6) * Mean ± SD; n (%)