PT - JOURNAL ARTICLE AU - Blair Westerly AU - Geoffrey Johnson AU - Fabien Maldonado AU - James Utz AU - Ulrich Specks AU - Tobias Peikert TI - B-lymphocyte targeted therapy for patients with progressive fibrosing mediastinitis DP - 2014 Sep 01 TA - European Respiratory Journal PG - 4636 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/4636.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/4636.full SO - Eur Respir J2014 Sep 01; 44 AB - Background: Fibrosing Mediastinitis (FM) is an idiosyncratic fibro-inflammatory syndrome characterized by the progressive proliferation of fibrous tissue in the mediastinum. In North America it is most commonly associated with Histoplasma infection. Clinical disease manifestations of FM are directly related to the compression and compromise of vital mediastinal structures. Patients with progressive bilateral FM face high morbidity and mortality. There are currently no effective medical treatment options. We previously demonstrated prominent B-lymphocyte infiltration in FM.Hypothesis:B-lymphocytes may promote the fibro-inflammatory response in FM and their depletion using rituximab may represent a novel therapeutic alternative.Methods: Prospective off label therapy of 3 patients with progressive and/or bilateral metabolically active (FDG-PET/CT positive) FM with rituximab. Patient 1 received 375 mg/m2 of rituximab for 4 weekly doses, and patients 2 and 3 were treated with 1000 mg of rituximab twice 15 days apart. All patients received a 2 months taper of Prednisone and Bactrim for pneumocystis pneumonia prophylaxis. Clinical, radiological and metabolic responses were recorded.Results: Circulating B-lymphocytes were depleted. There were no severe side effects. All patients had favorable therapeutic responses. The lesion resolved in patient 1 and steroids were tapered successfully. Patients 2 and 3 experienced a dramatic symptomatic improvement and resolution of pleural effusion (Patient 2). Patients 2 and 3 had significant metabolic responses by FDG-PET/CT and lesions size decreased in Patient 3 by CT.Conclusion:B-lymphocyte depletion with rituximab may be the first effective therapy for FM.