The Incidence and Predisposing Factors of John Cunningham Virus-Induced Progressive Multifocal Leukoencephalopathy in Southern Finland: A Population-Based Study

Abstract

Background The aim of this study was to assess the prevalence, incidence rate (IR), predisposing factors, survival rate, and diagnostic delay of progressive multifocal leukoencephalopathy (PML) across medical specialties. Another objective was to survey how PML diagnosis was made in the studied cases. Methods This is a cross-sectional retrospective observational study of PML cases across different medical specialties during 2004–2016 in the Finnish Capital Region and Southern Finland. Data were obtained from clinical records, clinical microbiology, pathology and radiology department records, and human immunodeficiency virus (HIV) quality register medical records. Results A total of 31 patients were diagnosed with PML. The prevalence of PML was 1.56 per 100 000 people and the IR was 0.12 per 100 000 individuals per year during 2004–2016. Hematologic malignancies (n = 19) and HIV/acquired immune deficiency syndrome (n = 5) were the most common underlying diseases, and all patients who had malignant diseases had received cancer treatment. Before PML diagnosis, 21 (67.7%) patients were treated with chemotherapy, 14 (45.2%) patients with rituximab, and 1 patient (3.2%) with natalizumab. Two patients (6.5%) had no obvious immunocompromising disease or treatment. Neither gender, age, first symptoms, previous medication, nor underlying disease influenced the survival of PML patients significantly. The 5-year survival rate was poor, at less than 10%. Conclusions The majority of PML patients in our study had a predisposing disease or had immunosuppressive or monoclonal antibody therapy. In the future, broader use of immunosuppressive and immunomodulatory medications may increase incidence of PML among patients with diseases unassociated with PML. Safety screening protocols for John Cunningham virus and PML are important to prevent new PML cases.

<p>Progressive Multifocal Leukoencephalopathy: Current Insights</p>

“…Finnish population-based registry study investigating the period 2004–2014 reported an overall lower PML incidence of 0.072/100,000 person-years with no temporal incidence trend despite the increasing use of mAbs at the national level 27. In the most recent study from southern Finland in 2004–2016, we reported a PML-incidence of 0.12/100,000 person-years with no sign of increase 28. In this study the data was obtained from clinical records and the HIV Quality Registry.…”

“…Increased use of mAbs and HSCT correlate with rising PML incidence among patients with hematologic malignancies 30. Hematologic conditions associated with PML include CLL, Hodgkin’s disease, non-Hodgkin’s lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, Waldeström macroglobulinemia, multiple myeloma, polycythemia vera, and mycosis fungoides 28,29,31. Major PML risk factors are uncontrolled Hodgkin’s disease, treatment with purine analogues, and treatments related to HSCT 32.…”

“…Some cases of PML have been reported with less overt immunodeficiency, such as chronic kidney and liver diseases, type 2 diabetes mellitus, dementia 28,49. There is one histologically proven PML case each concerning a pregnant woman, and a woman prior to pregnancy without any known underlying immunodeficiency 50,51.…”

Fifty Years of JC Polyomavirus: A Brief Overview and Remaining Questions

“…While the fatality rate of PML has been significantly reduced by restoration of immune function and most PML patients now survive, most experience significant morbidity [42][43][44][45]. HIV-associated PML still remains one of the most common types of PML, but no longer accounts for the overwhelming majority of new cases due to the availability of HAART and the emergence of new risk factors for PML [46,47]. Though it is one of the only treatments available for PML, restoration of immune function needs be carefully managed because it can lead to a fatal inflammatory reaction called immune reconstitution inflammatory syndrome or IRIS [48][49][50].…”

“…As such, other classifications of PML are exceedingly rare [58,59]. The prevalence of PML worldwide is often estimated to be about two cases per 100,000 individuals, though this number varies by population [47,60].…”