Mortality in People Diagnosed With Progressive Multifocal Leukoencephalopathy: A Systematic Literature Review

OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by reactivation of latent JC polyomavirus. Understanding of the clinical course and burden of PML, including survival estimates, is limited by its rarity. This systematic literature review (SLR) and synthesis of case report data aimed to better understand mortality occurrence among people diagnosed with PML.

METHODS: An SLR was conducted in PubMed® in October 2023. Case reports and series of individuals with diagnosed PML were included, if age at last visit or death was reported. For people reported in multiple publications, one combined summary was generated per unique patient. Demographics and clinical data of interest were extracted and quality controlled by two independent reviewers.

RESULTS: From the 213 studies that met the inclusion criteria, 323 individuals with PML were identified (36% female, 57% male, 7% sex not reported). Mean (range) age at diagnosis (n=319), and last follow-up (n=323) were 52.6 (6.0-87.0) and 53.9 (6.5-87.1) years, respectively. Mean follow up from symptom onset to diagnosis (n=224) was 2.6 (0-48.0) months. Mean follow up time from diagnosis to last follow up or death was 13.5 (0-156.0) months. Of the 323 cases reported, 53% were from Europe, 31% from the Americas, 12% from the Western Pacific, 3% from South East Asia and 1% from the Eastern Mediterranean region. In total, 143 deaths were reported, occurring at mean age 56.2 years (range, 13.1-87.1). Mean follow up time from diagnosis to death (n=143) was 5.1 (0-69.0) months. Of the 143 events, 90 (63%) occurred within 3 months from diagnosis.

CONCLUSIONS: To our knowledge, this is the most current SLR of mortality among individuals with PML. These findings underscore the pressing need for targeted treatments to improve outcomes and extend survival.