Long-term outcomes of allogeneic stem cell transplant recipients after calcineurin inhibitor-induced neurotoxicity

Authors

  • Rizwana Chohan,

  • Ravi Vij,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • Douglas Adkins,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • William Blum,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • Randy Brown,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • Michael Tomasson,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • Steven Devine,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • Timothy Graubert,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • Lawrence T. Goodnough,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • John F. DiPersio,

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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  • Hanna Khoury

    1. Washington University School of Medicine, Department of Medicine, Division of Oncology, Section of Leukaemia & Bone Marrow Transplantation, St Louis, MO, USA
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Hanna Khoury, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8007, St Louis, MO 63110-1093, USA. E-mail: HKhoury@im.wustl.edu

Abstract

Summary. Calcineurin inhibitor-induced central nervous system toxicities are uncommon and often resolve after discontinuation of the offending drug. The long-term outcome of these patients is, however, unknown. Resolution of symptoms occurred in 70% of 30 allografted recipients who developed calcineurin inhibitor-induced neurotoxicity. When patients were rechallenged with the same or a different calcineurin inhibitor, symptoms recurred in 41%, leading to permanent discontinuation of the drug. De novo or progressive acute graft-versus-host disease (GVHD) was observed in 54% of patients at a median of 7 d (range 1–70 d) after initial onset of neurotoxicity. The prognosis was grim, with 24 (80%) of these patients dying a median 33 d after the onset of neurotoxicity (range 2–594 d). GVHD and/or infection occurred in 54% and were the most common primary causes of death. We conclude that calcineurin inhibitor-induced neurotoxicity is frequently reversible but associated with a poor prognosis.

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