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NEUROLOGY 2009;73:1551-1558
© 2009 American Academy of Neurology

Determinants of survival in progressive multifocal leukoencephalopathy

A. Marzocchetti, PhD, T. Tompkins, BSc, D. B. Clifford, MD, R. T. Gandhi, MD, S. Kesari, MD, PhD, J. R. Berger, MD, D. M. Simpson, MD, M. Prosperi, PhD, A. De Luca, MD and I. J. Koralnik, MD

From the Division of Viral Pathogenesis (A.M., T.T., I.J.K.) and Department of Neurology (I.J.K.), BIDMC, Harvard Medical School, Boston, MA; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Department of Infectious Diseases (R.T.G.), MGH, Harvard Medical School, Boston, MA; Department of Neurology (S.K.), Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Department of Neurology (J.R.B.), University of Kentucky College of Medicine, Lexington; Department of Neurology (D.M.S.), Mount Sinai School of Medicine, New York, NY; Department of Virology (M.P.), National Institute of Infectious Diseases "L. Spallanzani," Rome; and Division of Infectious Diseases (A.D.L.), Catholic University, Rome, Italy.

Address correspondence and reprint requests to Dr. Igor J. Koralnik, Beth Israel Deaconess Medical Center, E/CLS-1005, 330 Brookline Ave., Boston, MA 02215 ikoralni{at}bidmc.harvard.edu

Background: We sought to characterize the role of immunologic, virologic, and radiologic determinants of survival in patients with progressive multifocal leukoencephalopathy (PML).

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/µL at PML diagnosis compared to 67% in those with CD4 >200/µL (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.

CE = contrast enhancement; CI = confidence interval; CTL = cytotoxic T-lymphocytes; HR = hazard ratio; IQR = interquartile range; IRIS = immune reconstitution inflammatory syndrome; JCV = JC virus; PBMC = peripheral blood mononuclear cells; PML = progressive multifocal leukoencephalopathy.

Supported in part by NIH grant R01 NS041198 and 047029, and K24 NS 060950 to I.J.K., and the Harvard Medical School Center for AIDS Research (CFAR), an NIH-funded program (P30 AI60354).

Disclosure: Author disclosures are provided at the end of the article.

Received March 31, 2009. Accepted in final form July 30, 2009.






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