Progressive multifocal leukoencephalopathy and malignant lymphoma of the brain in a patient with immunosuppressive therapy

Ho, K C; Garancis, John C.; Paegle, Roland D.; Gerber, Michael A.; Borkowski, Winslow J.

doi:10.1007/bf00687233

Cited by 32 publications

(7 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Six were derived from the non‐English medical literature. A total of 32 patients were reported in detail, including 3 lung,28–30 4 heart,31–34 6 liver,35–40 and 19 kidney4, 41–57 recipients (Fig 2). Among kidney transplants, graft was from a deceased donor (n = 9), living donor (n = 7), combined living and dead donors (n = 1), and unstated (n = 2).…”

Section: Resultsmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy in transplant recipients

Mateen

Muralidharan

Carone

et al. 2011

Annals of Neurology

161

137

View full text Add to dashboard Cite

Objective Transplant recipients are at risk of developing progressive multifocal leukoencephalopathy (PML), a rare demyelinating disorder caused by oligodendrocyte destruction by JC virus. Methods Reports of PML following transplantation were found using PubMed Entrez (1958–July 2010). A multicenter, retrospective cohort study also identified all cases of PML among transplant recipients diagnosed at Mayo Clinic, Johns Hopkins University, Washington University, and Amsterdam Academic Medical Center. At 1 institution, the incidence of posttransplantation PML was calculated. Results A total of 69 cases (44 solid organ, 25 bone marrow) of posttransplantation PML were found including 15 from the 4 medical centers and another 54 from the literature. The median time to development of first symptoms of PML following transplantation was longer in solid organ vs bone marrow recipients (27 vs 11 months, p = 0.0005, range of <1 to >240). Median survival following symptom onset was 6.4 months in solid organ vs 19.5 months in bone marrow recipients (p = 0.068). Case fatality was 84% (95% confidence interval [CI], 70.3–92.4%) and survival beyond 1 year was 55.7% (95% CI, 41.2–67.2%). The incidence of PML among heart and/or lung transplant recipients at 1 institution was 1.24 per 1,000 posttransplantation person-years (95% CI, 0.25–3.61). No clear association was found with any 1 immunosuppressant agent. No treatment provided demonstrable therapeutic benefit. Interpretation The risk of PML exists throughout the posttransplantation period. Bone marrow recipients survive longer than solid organ recipients but may have a lower median time to first symptoms of PML. Posttransplantation PML has a higher case fatality and may have a higher incidence than reported in human immunodeficiency virus (HIV) patients on highly-active antiretroviral therapy (HAART) or multiple sclerosis patients treated with natalizumab.

show abstract

Section: Resultsmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy in transplant recipients

Mateen

Muralidharan

Carone

et al. 2011

Annals of Neurology

161

137

View full text Add to dashboard Cite

show abstract

“…While viral DNA can be detected in these astrocytes by in situ hybridization (2), they rarely express late viral proteins (3). Although the morphology of the astrocytes suggests a neoplastic process, few cases of intracranial tumors have been associated with PML (32,55,74,88,172). Reactive astrocytosis, a nonspecific finding in many neuropathological processes, is also seen with PML.…”

Section: Pathology Of Pmlmentioning

confidence: 99%

Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.

Major

Amemiya

Tornatore

et al. 1992

Clinical Microbiology Reviews

104

View full text Add to dashboard Cite

ease are graphically presented in Fig. 1: (A) JC virions as they assemble in the nucleus of an infected cell in the brain; (B) glial cells, cultured from human brain, which are the targets of virus infection; (C) histopathological plaque lesion of white matter, stained for myelin, that results from that infection; (D) hematoxylin and eosin stain of cells in the lesion identified as macrophages (m) and astrocytes (a); and (E) plaques of demyelinated white matter which represent the neurological impairments characteristic of PML, shown here by magnetic resonance imaging (MRI). The term PML was originally used in 1958 to describe extensive demyelination associated with chronic lymphocytic leukemia (CLL) and Hogdkin's lymphoma (14). However, accounts of similar pathology in patients with dementia were detailed as early as 1930 by Hallervorden (85). A 49 on September 7, 2020 by guest http://cmr.asm.org/ Downloaded from Host Range Studies of JCV in Non-Brain-Derived Cells By using laboratory measurements of JCV growth such as hemagglutination activity, other cells from human and other species were tested for JCV susceptibility. At first, human embryonic kidney, lung, amnion, liver, and intestine were

show abstract

“…PML is an opportunistic disease that aects patients with an impaired immune system due to various illnesses, immunosuppressive therapeutic treatments, and genetic disorders (Astrom et al, 1958;Berger and Concha, 1995). In addition to its causative role in PML, several studies have reported detection of JCV PML variants such as Mad-1, Mad-4, etc., from a variety of human brain tumors (Castaigne et al, 1974;Egan et al, 1980;Ho et al, 1980;Liberski et al, 1982;Rencic et al, 1996;Sima et al, 1983). Although there is no direct evidence for tumorigenesis of JCV in the human CNS, the oncogenic potential of JCV(Mad) in several experimental models has been well established.…”

Section: Introductionmentioning

confidence: 99%

Human ubiquitous JCV(CY) T-antigen gene induces brain tumors in experimental animals

et al. 1999

View full text Add to dashboard Cite

JCV is a papovavirus which is widespread in the human population. The prototype Mad-1 variant of JCV induces a fatal demyelinating disease of the central nervous system (CNS) called Progressive Multifocal Leukoencephalopathy (PML) in immunosuppressed individuals. The unique tropism of JCV (Mad-1) to the CNS is attributed to the tissue-speci®c regulation of the viral early promoter which is responsible for the production of the viral regulatory protein, T-antigen. The archetype form of this virus, JCV(CY), which has been repeatedly isolated from the urine of PML and non-PML individuals, is distinct from JCV(Mad-1) in the structural organization of the regulatory sequence. To characterize the tissue speci®c expression of JCV(CY) and to investigate its potential in inducing disease, transgenic mice containing the early region of JCV(CY) were generated. Some of these mice between 9 ± 13 months of age exhibited signs of illness as manifested by paralysis of rear limbs, hunched posture, and poor grooming. Neuropathological examination indicated no sign of hypomyelination of the brain, but surprisingly, revealed the presence of primitive tumors originating from the cerebellum and the surrounding brain stem. The tumor masses also in®ltrated the surrounding tissue. Results from RNA and protein studies revealed a high level of Tantigen mRNA expression in hindbrains of clinically normal and aected transgenic mice. However, higher levels of T-antigen RNA and protein were detected in brains of the animals exhibiting severe illness. The close resemblance of JCV(CY) induced tumor in transgenic mice to the human medulloblastoma/primitive neuroectodermal tumor (PNETs) in location, histologic appearance, and expression of marker proteins strongly suggests the utility of this novel animal model for the study of human brain tumors.

show abstract

Progressive multifocal leukoencephalopathy and malignant lymphoma of the brain in a patient with immunosuppressive therapy

Cited by 32 publications

References 11 publications

Progressive multifocal leukoencephalopathy in transplant recipients

Progressive multifocal leukoencephalopathy in transplant recipients

Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.

Human ubiquitous JCV(CY) T-antigen gene induces brain tumors in experimental animals

Contact Info

Product

Resources

About