PMID- 34001660
OWN - NLM
STAT- MEDLINE
DCOM- 20220121
LR  - 20220121
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 8
IP  - 4
DP  - 2021 Jul
TI  - Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive 
      Multifocal Leukoencephalopathy.
LID - 10.1212/NXI.0000000000001020 [doi]
LID - e1020
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-gamma 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.
CI  - Copyright (c) 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Hopfner, Franziska
AU  - Hopfner F
AUID- ORCID: 0000-0001-6524-0281
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany. Hopfner.Franziska@mh-hannover.de.
FAU - Mohn, Nora
AU  - Mohn N
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Eiz-Vesper, Britta
AU  - Eiz-Vesper B
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Maecker-Kolhoff, Britta
AU  - Maecker-Kolhoff B
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Gottlieb, Jens
AU  - Gottlieb J
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Blasczyk, Rainer
AU  - Blasczyk R
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Mahmoudi, Nima
AU  - Mahmoudi N
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Pars, Kaweh
AU  - Pars K
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Adams, Ortwin
AU  - Adams O
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Stangel, Martin
AU  - Stangel M
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Wattjes, Mike P
AU  - Wattjes MP
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Hoglinger, Gunter
AU  - Hoglinger G
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
FAU - Skripuletz, Thomas
AU  - Skripuletz T
AD  - From the Department of Neurology (F.H., N. Mohn, 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 Dusseldorf, Germany.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20210517
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
SB  - IM
MH  - Aged
MH  - BK Virus/*immunology
MH  - *Cell Transplantation
MH  - Female
MH  - Humans
MH  - Leukoencephalopathy, Progressive Multifocal/*therapy
MH  - Middle Aged
MH  - T-Lymphocytes/*transplantation
PMC - PMC8130010
EDAT- 2021/05/19 06:00
MHDA- 2022/01/22 06:00
PMCR- 2021/05/17
CRDT- 2021/05/18 06:29
PHST- 2021/01/10 00:00 [received]
PHST- 2021/03/29 00:00 [accepted]
PHST- 2021/05/18 06:29 [entrez]
PHST- 2021/05/19 06:00 [pubmed]
PHST- 2022/01/22 06:00 [medline]
PHST- 2021/05/17 00:00 [pmc-release]
AID - 8/4/e1020 [pii]
AID - NEURIMMINFL2021038606 [pii]
AID - 10.1212/NXI.0000000000001020 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2021 May 17;8(4):e1020. doi: 
      10.1212/NXI.0000000000001020. Print 2021 Jul.