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10. Chapagain ML, Nerurkar VR. Humanpolyomavirus JC (JCV) infection of humanB lymphocytes: a possible mechanismfor JCV transmigration acrossthe blood-brain barrier. J Infect Dis.2010;202(2):184-191.11. Goldberg SL, Pecora AL, Alter RS, et al.Unusual viral infections (progressivemultifocal leukoencephalopathy and cytomegalovirusdisease) after high-dosechemotherapy with autologous bloodstem cell rescue and peritransplantationrituximab. Blood. 2002;99(4):1486-1488.12. Imperato AK, Bingham CO 3rd, AbramsonSB. Overview of benefit/risk of biologicalagents. Clin Exp Rheumatol. 2004;22(5Suppl 35):S108-S114.13. Kleinschmidt-DeMasters BK, Tyler KL.Progressive multifocal leukoencephalopathycomplicating treatment withnatalizumab and interferon beta-1afor multiple sclerosis. N Engl J Med.2005;353(4):369-374.14. Seminara NM, Gelfand JM. Assessinglong-term drug safety: lessons (re)learned from raptiva. Semin Cutan MedSurg. 2010;29(1):16-19.15. Data on file. Tysabri safety update.Weston, MA: Biogen Idec; June 2011.16. Sock E, Renner K, Feist D, et al. Functionalcomparison of PML-type andarchetype strains of JC virus. J Virol.1996;70(3):1512-1520.17. Tan CS, Dezube BJ, Bhargava P, et al. Detectionof JC virus DNA and proteins inthe bone marrow of HIV-positive andHIV-negative patients: implications forviral latency and neurotropic transformation.J Infect Dis. 2009;199(6):881-888.18. White FA 3rd, Ishaq M, Stoner GL, FrisqueRJ. JC virus DNA is present in many humanbrain samples from patients withoutprogressive multifocal leukoencephalopathy.J Virol. 1992;66(10):5726-5734.19. Sabath BF, Major EO. Traffic of JC virusfrom sites of initial infection to thebrain: the path to progressive multifocalleukoencephalopathy. J Infect Dis.2002;186(Suppl 2):S180-S186.20. Kamar N, Mengelle C, Rostaing L. Incidenceof JC-virus replication after rituximabtherapy in solid-organ transplantpatients. Am J Transplant. 2009;9(1):244-245.21. Wüthrich C, Kesari S, Kim WK, et al. Characterizationof lymphocytic infiltrates inprogressive multifocal leukoencephalopathy:co-localization of CD8(+) T cellswith JCV-infected glial cells. J Neurovirol.2006;12(2):116-128.22. Taoufik Y, Gasnault J, Karaterki A, et al.Prognostic value of JC virus load in cerebrospinalfluid of patients with progressivemultifocal leukoencephalopathy. JInfect Dis. 1998;178(6):1816-1820.23. De Luca A, Giancola ML, Ammassari A,et al. The effect of potent antiretroviraltherapy and JC virus load in cerebrospinalfluid on clinical outcome of patientswith AIDS-associated progressive multifocalleukoencephalopathy. J Infect Dis.2000;182(4):1077-1083.24. Marzocchetti A, Tompkins T, Clifford DB,et al. Determinants of survival in progressivemultifocal leukoencephalopathy.Neurology. 2009;73(19):1551-1558.25. Du Pasquier RA, Schmitz JE, Jean-JacquesJ, et al. Detection of JC virus-specific cytotoxicT lymphocytes in healthy individuals.J Virol. 2004;78(18):10206-10210.26. Garcia De Viedma D, Diaz Infantes M,Miralles P, et al. JC virus load in progressivemultifocal leukoencephalopathy:analysis of the correlation betweenthe viral burden in cerebrospinal fluid,patient survival, and the volume ofneurological lesions. Clin Infect Dis.2002;34(12):1568-1575.27. Delbue S, Branchetti E, Bertolacci S, etal. JC virus VP1 loop-specific polymorphismsare associated with favorableprognosis for progressive multifocalleukoencephalopathy. J Neurovirol. 2009;15(1):51-56.28. Gorelik L, Reid C, Testa M, et al. Progressivemultifocal leukoencephalopathy(PML) development is associated withmutations in JC virus capsid protein VP1that change its receptor specificity. J InfectDis. 2011;204(1):103-114.29. Bossolasco S, Calori G, Moretti F, et al.Prognostic significance of JC virus DNAlevels in cerebrospinal fluid of patientswith HIV-associated progressive multifocalleukoencephalopathy. Clin Infect Dis.2005;40(5):738-744.30. Gasnault J, Kousignian P, Kahraman M, etal. Cidofovir in AIDS-associated progressivemultifocal leukoencephalopathy: amonocenter observational study withclinical and JC virus load monitoring. JNeurovirol. 2001;7(4):375-381.31. Gorelik L, Lerner M, Bixler S, et al. Anti-JC virus antibodies: implications forPML risk stratification. Ann Neurol. 2010;68(3):295-303.S16 July 2011 • Clinical Reviews of JCV and PML
Progressive MultifocalLeukoencephalopathy:Survival StatisticsMoti L. Chapagain, PhDAssistant Researcher, Department ofTropical Medicine, Medical Microbiologyand Pharmacology, John A. Burns Schoolof Medicine, Honolulu, Hawaii.Dr. Chapagain has no conflicts of interest to disclose.IntroductionFrom a newly emergent, rare, and mysterious illnesspredominantly affecting patients with underlyinglymphoproliferative disorders or hematologicalmalignancies in the 1950s, 1,2 progressive multifocalleukoencephalopathy (PML) has evolved into oneof the most frequent conditions associated withacquired immunodeficiency syndrome (AIDS). 3,4Moreover, PML has recently emerged as a lifethreateningcomplication among individuals onimmunomodulatory monoclonal antibody therapyand dramatically impacted their utilization. 5-7While PML has been regarded by most observers asboth a rare and fatal disease, 8 recent occurances ofPML among individuals with monoclonal antibodytherapies expanded the epidemiological reach ofthe disease and widened concerns. However, thesemore recent manifestations of PML have also ledto important advances in detection and treatment.Since the introduction of highly active antiretroviraltherapy (HAART)/combination antiretroviraltherapy (cART) stemming from the AIDS epidemicthat began in the 1980s, HIV-positive patients withPML are living longer and enabling researchersand clinicians to better understand the disease. 8,9The development of an immune reconstitutioninflammatory syndrome (IRIS) as well as PML associatedwith monoclonal antibodies used in thetreatment of such disorders as multiple sclerosis(MS) has also contributed to improved descriptionof the characteristics of PML as well as advances inmanagement of the disease. 8 Indeed, survival ratesfrom recent series provide evidence in support ofreclassifying PML from a fatal disease to a chronicdisease. 9-11Clinical Reviews of JCV and PML • July 2011 S17
Page 1 and 2: A SUPPLEMENT TO NEUROLOGY REVIEWSCl
Page 3 and 4: An Overview of JC Virusand Progress
Page 5 and 6: cation. Although PML is generally c
Page 7 and 8: JCV exposure than those who are not
Page 9 and 10: 39. Weber F, Goldmann C, Krämer M,
Page 12 and 13: diseases, which represent an autoim
Page 14: tainment of JCV in the CNS as well
Page 19 and 20: TABLE 2 Different forms of PMLClass
Page 21 and 22: characteristic brain changes on mag
Page 23 and 24: with HIV-associated PML, recent stu
Page 25 and 26: Natalizumab, the first monoclonal a
Page 27: 22. Lebwohl M, Tyring SK, Hamilton

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