{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T20:26:26Z","timestamp":1794255986394,"version":"4.9.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"Importance<\/jats:title>Progressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine whether restoring the compromised immune system of patients with PML with directly isolated allogeneic virus\u2013specific (DIAVIS) T cells is a promising therapeutic strategy, especially if other curative options are absent.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>A retrospective case series of patients with PML who were treated with DIAVIS T cells was conducted between March 2020 and February 2022. T cells were isolated from healthy donors within 24 hours and targeted against the BK polyomavirus. Patients with PML were treated monocentrically. Eligibility for treatment with DIAVIS T cells was assessed for patients with confirmed PML, and exclusion criteria included stable PML disease and previous treatment with natalizumab.<\/jats:p><\/jats:sec>Exposure<\/jats:title>Fresh DIAVIS T cells were administered with a maximum dose of 2\u2009\u00d7\u2009104<\/jats:sup> CD3+ cells\/kg body weight. Remaining T cells were cryopreserved in divided doses and administered in additional treatments approximately 2 and 6 weeks later.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Primary outcome measures were clinical response and survival of patients, compared with the outcomes of a historical reference group of PML cases receiving best supportive treatment (BST) and with recently published real-world data of patients with PML who were treated with immune checkpoint inhibition.<\/jats:p><\/jats:sec>Results<\/jats:title>The study cohort consisted of 28 patients (median [IQR] age, 60 [51-72] years; 20 male [71.4%]). Twenty-two patients (79%) treated with DIAVIS T cells showed response, resulting in significant clinical stabilization or improvement and a reduction in viral load. Six individuals (21%) were classified as nonresponders, deteriorated rapidly, and died, as did 2 other patients during a 12-month follow-up. Older age was the only predictor of a poor treatment response. Survival analysis revealed better 12-month survival rates (hazard ratio, 0.42; 95% CI, 0.24-0.73; P<\/jats:italic> =.02) from diagnosis for patients treated with DIAVIS T cells (18 of 26 [69%]; 12-mo survival rate, 69%) compared with historical controls with BST (57 of 113 [50%]; 12-mo survival rate, including censored data, 45%).<\/jats:p><\/jats:sec>Conclusion and Relevance<\/jats:title>This case series of DIAVIS T-cell therapy in PML provides first class IV evidence suggesting efficacy to reduce mortality and improve functional outcome. Further prospective studies are required to confirm these results.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.3324","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T15:01:07Z","timestamp":1728313267000},"page":"1187","source":"Crossref","is-referenced-by-count":37,"title":["Directly Isolated Allogeneic Virus\u2013Specific T Cells in Progressive Multifocal Leukoencephalopathy"],"prefix":"10.1001","volume":"81","author":[{"given":"Nora","family":"M\u00f6hn","sequence":"first","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Grote-Levi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike P.","family":"Wattjes","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and 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