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Progressive multifocal leukoencephalopathy after durvalumab treatment for acute myeloid leukemia: A consequence of an immune reconstitution inflammatory syndrome?

ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system resulting from the reactivation of the John Cunningham virus (JCV). PML occurs almost exclusively during profound immune suppression but it can also be observed in immunocompromised subjects as part of an inflammatory immune reconstitution syndrome (IRIS) in patients receiving antiviral therapy. We report a case of PML in a 61-year-old patient with acute myeloid leukemia who had developed after discontinuation of durvalumab (anti-PD-L1) therapy initiated after multiple treatments. Results suggest that PML may result from two nonexclusive mechanisms: (i) an inhibition of the protective response of JCV-specific T cells as a consequence of the blockade of the PD1-PDL1 pathway, associated with a lack of compensatory expression of other inhibitory receptors by T cells and (ii) a neuroinflammatory response (PML-IRIS) that may have contributed to virus reactivation.

SUBMITTER: Vinatier E

PROVIDER: S-EPMC9422031 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Progressive multifocal leukoencephalopathy after durvalumab treatment for acute myeloid leukemia: A consequence of an immune reconstitution inflammatory syndrome?

Vinatier Emeline E Poli Caroline C Giltat Aurélien A Nunes-Gomes Christopher C Orvain Corentin C Hunault-Berger Mathilde M Jeannin Pascale P Thépot Sylvain S

EJHaem 20220529 3

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system resulting from the reactivation of the John Cunningham virus (JCV). PML occurs almost exclusively during profound immune suppression but it can also be observed in immunocompromised subjects as part of an inflammatory immune reconstitution syndrome (IRIS) in patients receiving antiviral therapy. We report a case of PML in a 61-year-old patient with acute myeloid leukemia who had develo ...[more]

PMID: 36051020

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Project description:Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly progressive spastic hemi- or limb pareses as well as disturbances of vision, speech, and orientation. Cerebral magnetic resonance imaging showed T2-hyperintense, confluent, mainly supratentorial lesions. Four patients developed punctate contrast enhancement as a radiological sign of an immune reconstitution inflammatory syndrome (IRIS), three of them having a fatal course. In the cerebrospinal fluid, the initial JC virus load (8-25,787 copies/ml) did not correlate with interindividual severity; however, virus load corresponded to clinical dynamics. Brain biopsies (n = 2), performed 2 months after symptom onset, showed spotted demyelination and microglial activation. All patients had lymphopenia in the range of 270-1150/µl. To control JC virus, three patients received a combination of mirtazapine and mefloquine, another two patients additionally took cidofovir. One patient was treated with cidofovir only, and one patient had a combined regimen with mirtazapine, mefloquine, cidofovir, intravenous interleukin 2, and JC capsid vaccination. To treat sarcoidosis, the four previously untreated patients received prednisolone. Three patients had taken immunosuppressants prior to PML onset, which were subsequently stopped as a potential accelerator of opportunistic infections. After 6-54 months of follow up, three patients reached an incomplete recovery, one patient progressed, but survived so far, and two patients died. One further patient was additionally diagnosed with lung cancer, which he died from after 24 months. We conclude that the combination of PML and sarcoidosis is a diagnostic and therapeutic challenge. PML can occur as the first sign of sarcoidosis without preceding immunosuppressive treatment. The development of IRIS might be an indicator of poor outcome.

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Progressive multifocal leukoencephalopathy after durvalumab treatment for acute myeloid leukemia: A consequence of an immune reconstitution inflammatory syndrome?

Publications

Progressive multifocal leukoencephalopathy after durvalumab treatment for acute myeloid leukemia: A consequence of an immune reconstitution inflammatory syndrome?

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