Neurol Neuroimmunol Neuroinflamm 2021 07 17;8(4). Epub 2021 May 17.
From the Department of Neurology (F.H., N. Möhn, M.S., G.H., T.S.), Hannover Medical School; Institute of Transfusion Medicine and Transplant Engineering (B.E.-V., R.B.), Hannover Medical School; Department of Pediatric Hematology and Oncology (B.M.-K.), Hannover Medical School; Hannover Medical School (B.M.-K.), Institute for Transfusion Medicine; Department of Respiratory Medicine (J.G.), Hannover Medical School; Department of Diagnostic and Interventional Neuroradiology (N. Mahmoudi, M.P.W.), Hannover Medical School, Hannover; Department of Neurology (N. Mahmoudi, K.P., M.P.W.), Carl Von Ossietzky University, Oldenburg; and Institute of Virology (O.A.), Medical Faculty, Heinrich-Heine University Düsseldorf, Germany.
Objective: Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating opportunistic infection of the brain caused by the ubiquitously distributed JC polyomavirus. There are no established treatment options to stop or slow down disease progression. In 2018, a case series of 3 patients suggested the efficacy of allogeneic BK virus-specific T-cell (BKV-CTL) transplantation.
Methods: Two patients, a bilaterally lung transplanted patient on continuous immunosuppressive medication since 17 years and a patient with dermatomyositis treated with glucocorticosteroids, developed definite PML according to AAN diagnostic criteria. We transplanted both patients with allogeneic BKV-CTL from partially human leukocyte antigen (HLA) compatible donors. Donor T cells had directly been produced from leukapheresis by the CliniMACS IFN-γ cytokine capture system. In contrast to the previous series, we identified suitable donors by HLA typing in a preexamined registry and administered 1 log level less cells.
Results: Both patients' symptoms improved significantly within weeks. During the follow-up, a decrease in viral load in the CSF and a regression of the brain MRI changes occurred. The transfer seemed to induce endogenous BK and JC virus-specific T cells in the host.
Conclusions: We demonstrate that this optimized allogeneic BKV-CTL treatment paradigm represents a promising, innovative therapeutic option for PML and should be investigated in larger, controlled clinical trials.
Classification Of Evidence: This study provides Class IV evidence that for patients with PML, allogeneic transplant of BKV-CTL improved symptoms, reduced MRI changes, and decreased viral load.