RT Journal Article SR Electronic T1 Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 221 OP 232 DO 10.1183/09031936.00199312 VO 43 IS 1 A1 Katrin E. Hostettler A1 Jörg P. Halter A1 Sabine Gerull A1 Didier Lardinois A1 Spasenija Savic A1 Michael Roth A1 Michael Tamm YR 2014 UL http://erj.ersjournals.com/content/43/1/221.abstract AB Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS). Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [3H]-thymidine incorporation. Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1 of patients with bronchiolitis obliterans was unchanged. Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT. Calcineurin inhibitor-free regimens need further evaluation in bronchiolitis obliterans after stem cell transplantation http://ow.ly/qeKha