Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Neil, Elizabeth; DeAngelis, Lisa M.

doi:10.1182/bloodadvances.2017008201

Cited by 37 publications

(45 citation statements)

References 23 publications

(46 reference statements)

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“…This perception needs to change; however, the advances in antiretroviral therapy have reduced the risk of HIV-associated PML to <1%. The incidence of PML in haematological malignancies is 0.07%–0.52% per year and in 4–11 per 1000 patients with MS who are treated with natalizumab 1 4 5…”

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy following five lines of therapy and three autologous bone marrow transplants for multiple myeloma

et al. 2020

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A 59-year-old man, with a background of multiply relapsed myeloma, presented with a 3-week history of confusion, short-term memory impairment and behavioural changes. CT head showed bilateral white matter changes and numerous, large lytic lesions of the skull vault. MRI brain revealed multiple areas of hyperintensity on T2-weighted sequences which did not enhance (many of which showed diffusion restriction) unexpectedly bringing progressive multifocal leukoencephalopathy (PML) into the differential. Initial cerebrospinal fluid studies were largely unremarkable, aside from a mildly elevated protein; cultures were negative. PCR for the John Cunningham (JC) virus was positive. Considering the patient’s medical history and rapidily progressive symptoms, a palliative approach was adopted, with the patient dying 14 days later. We present this case as an example of PML in a patient with multiple myeloma, highlighting the need to consider this diagnosis in an enlarging population of heavily treated, severely immunocompromised, patients.

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Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy following five lines of therapy and three autologous bone marrow transplants for multiple myeloma

et al. 2020

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“…For diagnosis, cerebrospinal fluid (CSF) examination for presence of the JCV is advised (ultrasensitive PCR techniques have a sensitivity > 95%), with several authorities accepting positive CSF JCV, clinical and radiological findings as confirmatory of PML [27]. Notably, a potential exists for both false-negative and false-positive CSF JCV DNA results (even with ultrasensitive PCR) [28]. In these instances, clinical assessment is paramount; proceeding to brain biopsy in high-suspicion patients with negative CSF tests is appropriate, while low CSF JCV titres in patients lacking clinical and imaging evidence of PML should be followed up with repeat testing and consideration of other pathology.…”

Section: Discussionmentioning

confidence: 99%

Rapid cognitive decline in a patient with chronic lymphocytic leukaemia: a case report

Forryan

Yong

2020

J Med Case Reports

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Background: The use of monoclonal antibodies in various settings has been linked to the development of progressive multifocal leukoencephalopathy (PML). Whilst this association is well-described with agents such as rituximab and natalizumab, the literature describing the occurrence of PML with ofatumumab therapy (especially in a haematology setting) is sparse. This case aims to draw attention to the above association with a particular focus on the mechanisms by which B-cell-depleting therapy can precipitate PML during the treatment of haematological malignancy. Case presentation: A 68-year-old Caucasian man presented with acute-on-subacute confusion and reduced mobility. He had a history of chronic lymphocytic leukaemia for which he had completed six cycles of ofatumumab and chlorambucil 2 months prior to presentation. Biochemistry, physical examination and imaging were unremarkable on admission. Subsequent neurological examination demonstrated diminished reflexes and an extensor right plantar, while magnetic resonance imaging (MRI) assessment revealed white matter hyperintensities in the frontal lobes with restricted diffusion surrounding these areas. Cerebrospinal fluid (CSF) analysis demonstrated normal cell counts and chemistry but detected John Cunningham virus (JCV) via polymerase chain reaction (PCR), with a quantitative value of 41,850 gEg/ml. CSF immunophenotyping excluded malignant processes. A diagnosis of PML was confirmed, and with the support of palliative care, the patient was discharged to a hospice for ongoing care with the family's agreement. Conclusion: PML remains a rare complication of ofatumumab treatment. Nevertheless, clinicians should maintain a certain level of suspicion for this risk, especially in the context of patients presenting with clinical syndromes of encephalopathy and focal neurologic deficits. Furthermore, research to better our understanding of the manifold links between B-cell function and JCV regulation could provide valuable information for use in the future prevention and treatment of PML.

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“…Rituximab is also used off-label as an immunomodulatory therapy for renal transplant and other autoimmune disorders [22][23][24]. After more than 20 years of use, rituximab is considered a safe and effective immunomodulatory therapy; nevertheless, adverse events have been documented, most notably an increased risk of progressive multifocal leukoencephalopathy (PML) particularly for patients with haematological malignancies [25][26][27]. In contrast, reports of adenovirus disease in patients treated with rituximab are uncommon.…”

Section: Impact Statementmentioning

confidence: 99%

Epidemiological and molecular characterization of a novel adenovirus of squirrel monkeys after fatal infection during immunosuppression

et al. 2020

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Adenoviruses are a frequent cause of acute upper respiratory tract infections that can also cause disseminated disease in immunosuppressed patients. We identified a novel adenovirus, squirrel monkey adenovirus 1 (SqMAdV-1), as the cause of fatal infection in an immunocompromised squirrel monkey (Saimiri boliviensis) at the Keeling Center for Comparative Medicine and Research (KCCMR). Sequencing of SqMAdV-1 revealed that it is most closely related (80.4 % pairwise nucleotide identity) to the titi monkey (Plecturocebus cupreus) adenovirus (TMAdV). Although identified in the titi monkey, TMAdV is highly lethal in these monkeys, and they are not thought to be the natural host. While SqMAdV-1 is similar to other primate adenoviruses in size and genomic characteristics, a nucleotide polymorphism at the expected stop codon of the DNA polymerase gene results in a 126 amino acid extension at the carboxy terminus, a feature not previously observed among other primate adenoviruses. PCR testing and partial sequencing of 95 archived faecal samples from other squirrel monkeys (Saimiri boliviensis and Saimiri sciureus) housed at the KCCMR revealed the presence of three distinct, and apparently endemic species of adenoviruses. A grouping of ten squirrel monkey adenovirus variants has high similarity to SqMAdV-1. A single adenovirus variant (designated SqMAdV-3), detected in five monkeys, has similarity to tufted capuchin (Sapajus apella) adenoviruses. The largest group of adenovirus variants detected (designated SqMAdV-2.0–2.16) has very high similarity (93–99 %) to the TMAdV, suggesting that squirrel monkeys may be the natural host of the TMAdV.

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Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Abstract: Key Points Immunotherapy for treatment of hematological malignancies is immunosuppressive, and chronic immunosuppression is a risk factor for PML. Early diagnosis is vital for instituting prompt immune reconstitution as treatment; brain biopsy is necessary in suspicious cases.

Cited by 37 publications

References 23 publications

Progressive multifocal leukoencephalopathy following five lines of therapy and three autologous bone marrow transplants for multiple myeloma

Progressive multifocal leukoencephalopathy following five lines of therapy and three autologous bone marrow transplants for multiple myeloma

Rapid cognitive decline in a patient with chronic lymphocytic leukaemia: a case report

Epidemiological and molecular characterization of a novel adenovirus of squirrel monkeys after fatal infection during immunosuppression

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