Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Abstract

Progressive multifocal leukoencephalopathy (PML) is an uncommon opportunistic infection with high morbidity and mortality. This is an institutional review board-approved retrospective review of medical records identified by diagnostic coding for PML or John Cunningham virus (JCV) from 2000 to 2015. Inclusion criteria were cerebrospinal fluid (CSF) positive for JCV by polymerase chain reaction or brain biopsy-proven PML in non-HIV patients. There were 16 patients, 12 of whom were men (75%); the median age was 56 years (range, 31-71 years). All had hematologic malignancies (5 [31%] had chronic lymphocytic leukemia, 3 [19%] had acute myeloid leukemia, 3 had [19%] mantle cell lymphoma, and 1 patient each had acute lymphoblastic leukemia, Hodgkin lymphoma, myeloma, or B-cell lymphoma). One patient received no cancer-directed therapy. Of the remaining 15 patients, all received conventional chemotherapy, and 9 (60%) underwent transplant. Thirteen patients (87%) received immunomodulating therapy (predominantly rituximab). The median time from cancer diagnosis to PML diagnosis was 48.5 months. PML was diagnosed a median of 2.1 months from symptom onset; however, the median time to PML diagnosis was 5.4 months for the 4 patients presenting with a cerebellar syndrome. PML was diagnosed by CSF in 12 patients and brain biopsy in 4 following negative CSF test results. Median survival from PML diagnosis was 4.3 months for the 11 patients on treatment and 0.87 months for the 5 without treatment. PML still occurs in patients with hematologic malignancies in the absence of treatment. Twenty-five percent of our patients required brain biopsy for diagnosis, and diagnosis was delayed when the clinical presentation was unusual, such as a cerebellar syndrome.

Graphical abstract

Figure 1.

Serial imaging of a patient diagnosed with CLL. Cancer-directed therapy included >6 months of rituximab and idelalisib. (A) Initial magnetic resonance imaging performed 2 months after the onset of headaches and balance disturbance (gait instability and repeated falls) depicting the asymmetric atrophy of the left cerebellum, which was not present in imaging performed 7 months earlier (not depicted). Fluid-attenuated inversion recovery (FLAIR) signal abnormalities are not present elsewhere. (B) Imaging repeated 3 months later (1 month prior to death) showing the continued atrophy of the left cerebellum with new confluent areas of FLAIR signal throughout the left cerebellum and left cerebellar peduncle without enhancement. Again, no FLAIR signal abnormalities are seen in the cerebrum.