
Contents
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Introduction Introduction
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Direct neurotoxicity Direct neurotoxicity
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General aspects General aspects
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Specific neurological syndromes Specific neurological syndromes
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Acute/subacute global encephalopathy Acute/subacute global encephalopathy
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Delayed leukoencephalopathy with stroke-like presentation Delayed leukoencephalopathy with stroke-like presentation
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Ifosfamide toxicity Ifosfamide toxicity
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Busulfan toxicity Busulfan toxicity
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Fludarabine toxicity Fludarabine toxicity
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Chronic encephalopathy Chronic encephalopathy
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Cerebellar toxicity Cerebellar toxicity
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Aseptic/chemical meningitis Aseptic/chemical meningitis
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Toxic peripheral neuropathies Toxic peripheral neuropathies
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Vinca alkaloids Vinca alkaloids
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Platinum compounds Platinum compounds
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Proteasome inhibitors Proteasome inhibitors
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Thalidomide and analogues Thalidomide and analogues
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Brentuximab vedotin Brentuximab vedotin
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Malnutrition/metabolic disorders Malnutrition/metabolic disorders
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Wernicke encephalopathy Wernicke encephalopathy
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Tumour lysis syndrome Tumour lysis syndrome
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Corticosteroid myopathy Corticosteroid myopathy
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Neurovascular complications Neurovascular complications
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Dural sinus thrombosis in asparaginase recipients Dural sinus thrombosis in asparaginase recipients
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Posterior reversible encephalopathy syndrome Posterior reversible encephalopathy syndrome
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Neuroimmunological complications Neuroimmunological complications
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Checkpoint inhibitors, antibodies targeting immune cells, and bispecific antibodies Checkpoint inhibitors, antibodies targeting immune cells, and bispecific antibodies
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Chimeric antigen receptor T cells Chimeric antigen receptor T cells
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Haemophagocytic lymphohistiocytosis Haemophagocytic lymphohistiocytosis
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Graft-versus-host disease Graft-versus-host disease
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Immune reconstitution inflammatory syndrome Immune reconstitution inflammatory syndrome
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Opportunistic infections Opportunistic infections
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Viral infections Viral infections
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Progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy
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Varicella-zoster infections Varicella-zoster infections
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Human herpesvirus 6 Human herpesvirus 6
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Fungal infections Fungal infections
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Parasitic infections Parasitic infections
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Toxoplasmosis Toxoplasmosis
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Neoplastic disorders Neoplastic disorders
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Post-transplant lymphoproliferative disorder Post-transplant lymphoproliferative disorder
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Disorders of CSF circulation Disorders of CSF circulation
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Pseudotumor cerebri in recipients of all-trans retinoic acid Pseudotumor cerebri in recipients of all-trans retinoic acid
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References References
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8 Neurological complications of medical therapies in haematological malignancies
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Published:July 2024
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Abstract
Medical therapies, including conventional chemotherapies and newer targeted and immunotherapies, used in haematological malignancies can give rise to a large spectrum of neurological complications either by direct neurotoxicity of the agents or by resulting from intricate effects on cell metabolism, coagulation, the innate and adaptive immune systems, and cerebrospinal fluid (CSF) homeostasis. Multiple drugs used for haematological malignancies can cause central neurotoxicity, manifested by acute or subacute global encephalopathy (busulfan, ifosfamide, intravenous methotrexate, fludarabine), chronic encephalopathy (intravenous methotrexate), a cerebellar syndrome (cytarabine), and aseptic meningitis (intrathecal methotrexate). Peripheral neuropathies are common with vinca alkaloids, proteasome inhibitors, platinum compounds, thalidomide and its analogues, and brentuximab vedotin. Tumour lysis syndrome can manifest with seizures and neuromuscular symptoms. Dural sinus thrombosis is a major risk specific to patients receiving asparaginase. An increasing number of agents have been associated with posterior reversible encephalopathy syndrome. Neuroimmunological complications, initially encountered mainly in the form of haemophagocytic lymphohistiocytosis and central nervous system involvement by graft-versus-host disease after allogeneic stem cell transplantation, are occurring more frequently with the use of immunotherapies, including checkpoint inhibitors, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies. The intrinsic risk of opportunistic infections encountered in haematological malignancies is further increased by specific therapeutic interventions, especially haematopoietic stem cell transplantation. Disorders of CSF circulation may occur in patients receiving all-trans retinoic acid. While many of the mechanisms underlying treatment-related neurotoxicities are unknown, haematologists must be aware of these disorders and be able to distinguish them from neurological involvement by the haematological disease itself. Prompt recognition enables the treating multidisciplinary medical team to interrupt the responsible treatment, initiate therapy, and reduce morbidity.
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