Birgitta Versluijs

112 Methods patients with very high-risk malignancies (relapsed myeloid leukemia and early relapsed lymphoid leukemia) receiving a cord blood (CB) donor, we omitted antithymocyte globu- lin from December 2012 onward. Stool samples and nose/throat swabs were cultured weekly to monitor for bacterial co- lonization. Plasma was tested weekly for the presence of EBV, cytomegalovirus, human herpesvirus 6, and adenovirus DNA by using real-time PCR. Weekly galactomannan tes- ting (Platelia Aspergillus enzyme immunoassay; Bio-Rad Laboratories, Hercules, Calif ) was performed to screen for Aspergillus species infection. Antimicrobial prophylaxis involved daily ciprofloxacin and fluconazole during neutrope- nia, with additional prophylaxis against Streptococcus viridans with cefazolin in the mu- cositis phase. Pneumocystis jirovecii pneumonia prophylaxis was administered as co-trim- oxazole 3 times a week. In case of positive serologic results for herpes simplex virus (in all patients) and varicella zoster virus (in CB recipients), prophylaxis with acyclovir was given. No other antiviral prophylaxis was given. In high-risk patients for invasive fun- gal infection, Aspergillus species prophylaxis was done with daily voriconazole or twice- weekly amphotericin B. GVHD prophylaxis consisted of cyclosporine (through a level of 150-250 mg/L) in all patients. In CB recipients we added prednisolone (1 mg/kg/d for 28 days); in patients receiving an unrelated volunteer donor transplant, methotrexate (short course, 10 mg/m 2 on days 1, 3, and 6) was added to cyclosporine. From 2013, we also administered a short course of methotrexate to patients receiving bone marrow from an HLA-matched sibling. Treatment of allo-LSs consisted of 10mg/kg/d intravenous methylprednisolone for 3 days and 2 mg/kg/d thereafter, tapering by 25% per week to 0.5 mg/kg/d. Methylprednisolone pulses were repeated monthly until recovery up to a maximum of 6 pulses. Recovery was defined as normalization of PFTs, resolved symptoms, or both. In between subsequent pulses, 0.5 mg/kg/d prednisone was administered. Other immunosuppressive agents (usually cyclosporine) were continued. In addition, azithromycin was given because of its suggested immunomodulatory effect. Along with immunosuppressive therapy, sup- portive care was provided with extra oxygen and mechanical ventilation, when necessary. Outcomes The main outcome of interest was the occurrence of allo-LSs, which were defined as idiopathic pneumonia syndrome (IPS) or bronchiolitis obliterans syndrome (BOS). IPS is defined by the American Thoracic Society as evidence of widespread lung injury by clinical symptoms and radiologic abnormalities in the absence of active lower respiratory tract infection and other factors explaining pulmonary dysfunction (cardiac dysfunction, fluid overload, or renal failure). 9 BOS is defined according to the National Institutes of Health Consensus Criteria on Chronic GVHD 2014 as an FEV1/vital capacity ratio of less 7