RT Journal Article
SR Electronic
T1 Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive Multifocal Leukoencephalopathy
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1020
DO 10.1212/NXI.0000000000001020
VO 8
IS 4
A1 Franziska Hopfner
A1 Nora Möhn
A1 Britta Eiz-Vesper
A1 Britta Maecker-Kolhoff
A1 Jens Gottlieb
A1 Rainer Blasczyk
A1 Nima Mahmoudi
A1 Kaweh Pars
A1 Ortwin Adams
A1 Martin Stangel
A1 Mike P. Wattjes
A1 Günter Höglinger
A1 Thomas Skripuletz
YR 2021
UL http://nn.neurology.org/content/8/4/e1020.abstract
AB 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.BKV-CTL=BK virus-specific T-cell; HLA=human leukocyte antigen; PML=progressive multifocal leukoencephalopathy; JCPyV=JC polyomavirus; JCVAI=anti-JC virus antibody index