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@ARTICLE{Goereci:885839,
      author       = {Goereci, Y. and Schweitzer, F. and Wellstein, A. and
                      Silling, S. and Borchmann, S. and Tresckow, B. and Adams, O.
                      and Martin, R. and Schlamann, M. and Schroeter, M. and Fink,
                      G. R. and Wattjes, M. P. and Warnke, C.},
      title        = {{C}learance of {JC} polyomavirus from cerebrospinal fluid
                      following treatment with interleukin‐2 and pembrolizumab
                      in an individual with progressive multifocal
                      leukoencephalopathy and no underlying immune deficiency
                      syndrome},
      journal      = {European journal of neurology},
      volume       = {27},
      number       = {11},
      issn         = {1351-5101},
      address      = {Oxford},
      publisher    = {Blackwell Science91133},
      reportid     = {FZJ-2020-04125},
      pages        = {2375-2377},
      year         = {2020},
      abstract     = {A 71‐year‐old Caucasian man presented with dysarthria
                      and fluctuating hypoesthesia of the right upper limb in
                      early 2019. Brain magnetic resonance imaging (MRI)
                      demonstrated T2/fluid attenuated inversion recovery
                      hyperintense lesions in the left parietal cortical grey
                      matter and adjacent white matter compatible with embolic
                      stroke of undetermined source. Eight weeks later, symptoms
                      had further progressed with loss of adequate communication,
                      disturbance of fine motor skills, ataxia and
                      neuropsychiatric symptoms. Widespread disease on brain MRI
                      and the detection of JC polyomavirus (JCPyV) DNA from
                      cerebrospinal fluid (CSF) confirmed the diagnosis of
                      progressive multifocal leukoencephalopathy (PML) [1]. Bone
                      marrow biopsy revealed normal findings, and no underlying
                      cause of reduced immunocompetence was identified. Despite
                      rehabilitation, treatment with mirtazapine and two cycles of
                      interleukin‐2 (IL‐2) (1 mio IE/m² sc once per day for 7
                      days) administered 2 weeks apart [1, 2], symptoms and MRI
                      lesions further progressed, with complete immobility and
                      severe dysphagia. Nine weeks after definite PML diagnosis
                      and 4 weeks after the last IL‐2 dose, a total of three
                      cycles of monthly infusions of pembrolizumab were applied.
                      At the initiation of the third cycle of pembrolizumab,
                      cognitive performance and fine motor skills had temporarily
                      improved, and the patient had regained the ability to walk a
                      few steps with assistance. On MRI, no increase in lesion
                      load and no signs of an immune reconstitution inflammatory
                      syndrome were noted. JCPyV DNA, after a decline that started
                      already following the IL‐2 therapy, was no longer detected
                      in CSF, collectively suggesting PML remission (Fig. 1).
                      Enzyme‐linked immunosorbent assays revealed increasing
                      JCPyV‐specific antibody titers in blood and CSF (AIJCPyV >
                      1.5 [3]). A pembrolizumab effect was indicated by reduced
                      programmed cell death protein 1 (PD‐1) expression on
                      peripheral CD4+ and CD8+ T cells after the treatment. Also,
                      during the disease course of PML and following pembrolizumab
                      treatment, proportions of innate immune cells
                      (CD56dimCD16‐cytotoxic NK cells, CD14+ CD16 classical and
                      CD14dim CD16+ non‐classical monocytes and CD11+ dendritic
                      cells) and pro‐inflammatory cytokines and chemokine
                      increased (Appendix S1, Table S1). Four weeks following the
                      last infusion with pembrolizumab, aspiration pneumonia was
                      suspected, and the patient received intravenous
                      piperacillin/tazobactam 4/0.5 g three times per day for 7
                      days with temporary relief of symptoms. No causative
                      bacteria were detected from blood cultures. Six weeks
                      post‐pembrolizumab treatment, respiratory distress
                      occurred again, and the general clinical condition further
                      deteriorated. The patient and his legal custodians decided
                      not to receive further hospital care, upon considering the
                      severe and persistent disability, and the patient died
                      shortly thereafter. As an autopsy was not performed,
                      alternative causes of respiratory distress, such as
                      autoimmune pneumonitis that might occur as an adverse event
                      of pembrolizumab therapy, could not be ruled out.},
      cin          = {INM-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32644211},
      UT           = {WOS:000578714700048},
      doi          = {10.1111/ene.14435},
      url          = {https://juser.fz-juelich.de/record/885839},
}