title: Progressive multifocal leukoencephalopathy following oral fludarabine treatment of chronic lymphocytic leukemia.
abstract: Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disorder of the central nervous system usually affecting immunocompromised individuals and is due to infection of the oligodendrocytes by the JC virus. A case of PML in a chronic lymphocytic leukemia (CLL) patient treated with fludarabine is reported, representing the second such instance in which the diagnosis of the neurological disorder was established by brain biopsy. A 61-year-old man with a 14-year history of B-cell type CLL, for which he had received chlorambucil therapy 10 years earlier, developed progressive paresis of both left extremities at 7 months of receiving low doses of oral fludarabine, when his CD4 count has decreased to 0.08 x 10(9)/l. Cranial magnetic resonance imaging revealed a subcortical focal lesion at the right precentral gyrus and a focal lesion at the right thalamus, and a stereotactic brain biopsy showed pathological findings consistent with PML, namely severe myelin breakdown, reactive astrocytosis, and abnormal, huge glial cells with large bizarre nuclei showing granular basophilic inclusions, whereas the presence of the JC virus was demonstrated by in situ hybridization. The present case, in addition to a few previously reported, calls attention to the possibility that severe neurological side effects can be associated with the immunosuppression provoked by the use of fludarabine in CLL patients.
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Cid
authors.forename: M
authors.initials: M
authors.lastname: Revilla
authors.forename: A
authors.initials: A
authors.lastname: Cervera
authors.forename: F
authors.initials: F
authors.lastname: Cervantes
authors.forename: E
authors.initials: E
authors.lastname: Muñoz
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.forename: E
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001706:Biopsy / Q000379:methods; D001921:Brain / Q000473:pathology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D013238:Stereotaxic Techniques; D014740:Vidarabine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine