Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Hostettler, K. E. and Halter, J. P. and Gerull, S. and Lardinois, D. and Savic, S. and Roth, M. and Tamm, M.. (2014) Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation. The European respiratory journal, Vol. 43, H. 1. pp. 221-232.

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Official URL: http://edoc.unibas.ch/dok/A6338067

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Bronchiolitis obliterans (BO) is a complication after allogeneic hematopoietic stem cell transplantation (HSCT). BO-management 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).Methods: Cells were isolated from surgical lung biopsies of 8 HSCT-patients with BOS. Proliferation was assessed by [3H]-thymidine-incorporation.Results: Biopsies revealed constrictive BO in 3 and lymphocytic bronchiolitis (LB) in 5 patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Co-stimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under the triple-therapy demonstrated that patients with LB had a significant improvement of their FEV1, whereas FEV1 of patients with BO was unchanged.Conclusion: Our data demonstrate a pro-poliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed anti-proliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with BO after HSCT.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
UniBasel Contributors:Tamm, Michael and Roth-Chiarello, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:59
Deposited On:06 Feb 2015 09:59

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