Successful outcome of progressive multifocal leukoencephalopathy with cytarabine and interferon

Steiger, M. J.; Tarnesby, Georgia; Gabe, S.M.; McLaughlin, James E.; Schapira, Anthony H.V.

doi:10.1002/ana.410330415

Cited by 64 publications

(21 citation statements)

References 13 publications

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“…Ara-C and, to a lesser extent, AZT have been shown to limit JCV replication in a tissue culture model (196) but to vary in their ability to inhibit JCV in PML patients in vivo. Ara-C monotherapy (7,59,109,159,274,313,364,376,393) or in combination with CDV (81,184,492,520), methotrexate (162), or interferon (159,189,471) has been reported with positive prognosis in some cases and death in other cases (18,89,180,195,204,346,404,462,502). The ACTG 243 clinical trial showed no benefit in survival rates for PML patients treated with either intrathecal or intravenous administration of Ara-C.…”

Section: Treatment Of Pml and Pml-irismentioning

confidence: 99%

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

et al. 2012

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SUMMARY Progressive multifocal leukoencephalopathy (PML) is a debilitating and frequently fatal central nervous system (CNS) demyelinating disease caused by JC virus (JCV), for which there is currently no effective treatment. Lytic infection of oligodendrocytes in the brain leads to their eventual destruction and progressive demyelination, resulting in multiple foci of lesions in the white matter of the brain. Before the mid-1980s, PML was a relatively rare disease, reported to occur primarily in those with underlying neoplastic conditions affecting immune function and, more rarely, in allograft recipients receiving immunosuppressive drugs. However, with the onset of the AIDS pandemic, the incidence of PML has increased dramatically. Approximately 3 to 5% of HIV-infected individuals will develop PML, which is classified as an AIDS-defining illness. In addition, the recent advent of humanized monoclonal antibody therapy for the treatment of autoimmune inflammatory diseases such as multiple sclerosis (MS) and Crohn's disease has also led to an increased risk of PML as a side effect of immunotherapy. Thus, the study of JCV and the elucidation of the underlying causes of PML are important and active areas of research that may lead to new insights into immune function and host antiviral defense, as well as to potential new therapies.

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Section: Treatment Of Pml and Pml-irismentioning

confidence: 99%

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

et al. 2012

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“…Although highly active antiretroviral therapy (HAART) has significantly reduced PML-associated mortality, its complications include the development of immune reconstitution inflammatory syndrome [5] and no clear survival benefit in patients with high baseline JCV loads in cerebrospinal fluid (CSF) [6,7]. Type I interferons (IFN-a and -b), best known for their antiviral and immunomodulatory properties, have been administered during both the pre-and post-HAART eras to patients with PML [8][9][10][11]. However, the outcomes have been controversial [8,9,11].…”

mentioning

confidence: 99%

“…Type I interferons (IFN-a and -b), best known for their antiviral and immunomodulatory properties, have been administered during both the pre-and post-HAART eras to patients with PML [8][9][10][11]. However, the outcomes have been controversial [8,9,11]. At present, there are no in vitro studies evaluating the direct antiviral effect of IFN-a or -b on JCV in infected target cells, and such studies are warranted [12].…”

mentioning

confidence: 99%

Interferon‐α and ‐β Restrict Polyomavirus JC Replication in Primary Human Fetal Glial Cells: Implications for Progressive Multifocal Leukoencephalopathy Therapy

Co¹,

Verma²,

Gurjav

et al. 2007

J INFECT DIS

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One of the major limitations of highly active antiretroviral therapy is its inability to inhibit the replication of polyomavirus JC (JCV), the etiologic agent of progressive multifocal leukoencephalopathy (PML), an acquired immunodeficiency syndrome-defining illness. We previously demonstrated the induction of interferon (IFN)-stimulated genes (ISGs) by JCV. In the present study, we characterize the specific viral events required to induce ISGs and the potential antiviral effects of type I IFN on JCV replication in human fetal glial cells in the presence and absence of type I IFNs. Productive JCV replication was essential for the induction of the antiviral host response. JCV replication at all steps was significantly inhibited in the presence of IFN, and neutralizing anti-IFN antibody rescued the inhibitory effect of IFN. These results support the use of IFN as an adjunct therapy for patients with PML. Because IFN cannot cross the blood-brain barrier to achieve its direct antiviral effect, intrathecal administration of IFN is warranted.

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“…In accordance with previous reports, thrombocytopenia was also interpreted as an adverse reaction to interferon. That interferon a is also beneficial in leukoencephalopathy has been shown in a case with progressive, multifocal leukoencephalopathy associated with sarcoidosis [17]. However, the effect has only been demonstrated in a single patient and may depend on the underlying cause of leukoencephalopathy.…”

Section: Discussionmentioning

confidence: 96%

Multifocal leukoencephalopathy and polyneuropathy after 18 years on interferon a

Finsterer¹,

Sommer

Stiskal

2005

Leukemia & Lymphoma

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Multifocal leukoencephalopathy and sensory-motor polyneuropathy have not been reported as side-effects of long-lasting interferon alpha therapy in a single patient. In a 77-year-old man interferon alpha2b and interferon alpha2a were administered subsequently but continuously since 1984 for hairy cell leukemia. Since early 2000, left-sided hemi-hypesthesia occurred and the patient developed gait disturbance, proximal weakness of the lower limbs, bilateral stocking-type sensory disturbances, and restless leg syndrome. Repeated cerebral magnetic resonance images showed multifocal T2-hyperintense white matter lesions supratentorially. The nerve conduction velocity of the peroneal and sural nerve was reduced. After exclusion of various differential diagnoses of leukoencephalopathy and application of a screening program for polyneuropathy, central and peripheral nervous system abnormalities were attributed to the long-lasting interferon alpha therapy. In single patients abnormally long-lasting interferon alpha therapy may cause multifocal white matter lesions supratentorially and sensory-motor polyneuropathy.

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Successful outcome of progressive multifocal leukoencephalopathy with cytarabine and interferon

Cited by 64 publications

References 13 publications

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

Interferon‐α and ‐β Restrict Polyomavirus JC Replication in Primary Human Fetal Glial Cells: Implications for Progressive Multifocal Leukoencephalopathy Therapy

Multifocal leukoencephalopathy and polyneuropathy after 18 years on interferon a

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