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Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation.
Eur Respir J 2014; 43(1):221-32ER

Abstract

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 [(3)H]-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.

Authors+Show Affiliations

University Hospital Basel, Basel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23645405

Citation

Hostettler, Katrin E., et al. "Calcineurin Inhibitors in Bronchiolitis Obliterans Syndrome Following Stem Cell Transplantation." The European Respiratory Journal, vol. 43, no. 1, 2014, pp. 221-32.
Hostettler KE, Halter JP, Gerull S, et al. Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation. Eur Respir J. 2014;43(1):221-32.
Hostettler, K. E., Halter, J. P., Gerull, S., Lardinois, D., Savic, S., Roth, M., & Tamm, M. (2014). Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation. The European Respiratory Journal, 43(1), pp. 221-32. doi:10.1183/09031936.00199312.
Hostettler KE, et al. Calcineurin Inhibitors in Bronchiolitis Obliterans Syndrome Following Stem Cell Transplantation. Eur Respir J. 2014;43(1):221-32. PubMed PMID: 23645405.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation. AU - Hostettler,Katrin E, AU - Halter,Jörg P, AU - Gerull,Sabine, AU - Lardinois,Didier, AU - Savic,Spasenija, AU - Roth,Michael, AU - Tamm,Michael, Y1 - 2013/05/03/ PY - 2013/5/7/entrez PY - 2013/5/7/pubmed PY - 2014/9/2/medline SP - 221 EP - 32 JF - The European respiratory journal JO - Eur. Respir. J. VL - 43 IS - 1 N2 - 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 [(3)H]-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. SN - 1399-3003 UR - https://www.unboundmedicine.com/medline/citation/23645405/Calcineurin_inhibitors_in_bronchiolitis_obliterans_syndrome_following_stem_cell_transplantation_ L2 - http://erj.ersjournals.com/cgi/pmidlookup?view=long&pmid=23645405 DB - PRIME DP - Unbound Medicine ER -