Abstract | BACKGROUND: METHODS: We recorded the clinical outcome of 60 patients with PML (73% HIV+) who were prospectively evaluated between 2000 and 2007 for the presence of JC virus (JCV)-specific CD8+ cytotoxic T-lymphocytes (CTL) in blood. RESULTS: Estimated probability of survival at 1 year was 52% for HIV+/PML and 58% for HIV- patients with PML. Patients with PML with detectable CTL within 3 months of diagnosis had a 1-year estimated survival of 73% compared to 46% for those without CTL (hazard ratio [HR] for death = 0.47, 95% confidence interval [CI] 0.13-1.75, p = 0.26). Patients with CTL response had an increased likelihood of having contrast enhancement of PML lesions and immune reconstitution inflammatory syndrome (odds ratio 3.7 and 7.8). Estimated 1-year survival was 48% in HIV+ patients with PML with CD4 count <200/microL at PML diagnosis compared to 67% in those with CD4 >200/microL (HR for death 1.41, 95% CI 0.27-7.38, p = 0.68). JCV DNA was detected in the urine of 48% and in the blood of 56% of patients with PML, but viruria and viremia were not associated with survival. CONCLUSIONS: The presence of JC virus (JCV)-specific cytotoxic T-lymphocytes (CTL) was associated with a trend toward longer survival in patients with progressive multifocal leukoencephalopathy (PML), which was more pronounced than the impact of CD4 count in HIV+ patients with PML early after diagnosis. Despite the association of contrast enhancement and immune reconstitution inflammatory syndrome with JCV-specific CTL, these cannot be considered as surrogate markers for the prognostic value of the CTL. Strategies aiming at improving the cellular immune response may improve the course of PML.
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Authors | A Marzocchetti, T Tompkins, D B Clifford, R T Gandhi, S Kesari, J R Berger, D M Simpson, M Prosperi, A De Luca, I J Koralnik |
Journal | Neurology
(Neurology)
Vol. 73
Issue 19
Pg. 1551-8
(Nov 10 2009)
ISSN: 1526-632X [Electronic] United States |
PMID | 19901246
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Biomarkers
(metabolism)
- Female
- Humans
- Immunity, Cellular
- JC Virus
(immunology)
- Leukoencephalopathy, Progressive Multifocal
(diagnosis, immunology, mortality, virology)
- Male
- Middle Aged
- Prospective Studies
- Survival Rate
(trends)
- T-Lymphocytes, Cytotoxic
(immunology, pathology, virology)
- Young Adult
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