title: Progressive Multifocal Leukoencephalopathy after Ibrutinib Therapy for Chronic Lymphocytic Leukemia.
abstract: Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton's tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lutz
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.
authors.forename: Arik B
authors.initials: AB
authors.lastname: Schulze
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.|Department of Internal Medicine, Marienhospital Osnabrück, Osnabrück, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rebber
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wiebe
authors.affiliation: Department of Clinical Radiology, University Hospital of Münster, Münster, Germany.
authors.forename: Tarek
authors.initials: T
authors.lastname: Zoubi
authors.affiliation: Department of Neurology, University Hospital of Münster, Münster, Germany.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Grauer
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Keßler
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kerkhoff
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.|Department of Translational Oncology, University Hospital of Münster, Münster, Germany.|Cluster of Excellence EXC 1003, Cells in Motion, Münster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.affiliation: Department of Medicine A, University Hospital of Münster, Münster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D018450:Disease Progression; D017809:Fatal Outcome; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000078785:Mirtazapine; D064847:Multimodal Imaging / Q000379:methods; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D008803:Mianserin; D000078785:Mirtazapine; D000225:Adenine; D015767:Mefloquine
keywords: B-Cell chronic lymphocytic leukemia; Ibrutinib; JC virus; Progressive multifocal leukoencephalopathy; Rituximab