Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

摘要: Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis comprises intensive immunosuppression, but treatment response poor. We investigated the effect cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on proliferation primary lung myofibroblasts from HSCT patients with syndrome (BOS). Cells were isolated surgical biopsies eight BOS. Proliferation was assessed by [(3)H]-thymidine incorporation. Biopsies revealed constrictive in three lymphocytic five patients. CsA FK506 significantly induced myofibroblasts. mPRED MMF caused significant inhibition proliferation, whereas had no effect. Costimulation FK506, inhibited proliferation. Serial pulmonary function tests over 12 months biopsy under triple therapy demonstrated that improvement forced expiratory volume 1 s (FEV1), FEV1 unchanged. Our data demonstrate pro-proliferative calcineurin inhibitors human obtained BOS HSCT. In contrast, based observed antiproliferative capacity vitro, MMF-based inhibitor-free strategies should be further evaluated