The black swan: a case of central nervous system graft-versus-host disease

Sara Butera; Rita Tavarozzi; Lucia Brunello; Paolo Rivela; Antonella Sofia; Lorenzo Viero; Michela Salvio; Marco Ladetto; Francesco Zallio

doi:10.1515/jbcpp-2023-0194

Article

The black swan: a case of central nervous system graft-versus-host disease

Sara Butera , Rita Tavarozzi , Lucia Brunello , Paolo Rivela , Antonella Sofia , Lorenzo Viero , Michela Salvio , Marco Ladetto and Francesco Zallio

Published/Copyright: October 17, 2023

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 34 Issue 6

Abstract

Objectives

Graft-versus-host disease (GVHD) of central nervous system is an atypical and rare manifestation of chronic GVHD, presenting with a heterogeneous spectrum of signs and symptoms. Diagnosis of neurological manifestations of GVHD can be highly challenging and remain associated with dismal prognosis, significant morbidity, and reduced quality of life.

Case presentation

In this report, we describe a 39-year-old woman developing neurological signs and symptoms 8 months after allogeneic HSCT magnetic resonance imaging showed multifocal hyperintense lesions involving the periventricular region and frontal subcortical white matter. There was no laboratory evidence of infective or malignant etiology, and the case was diagnosed as CNS-GVHD. The patient was treated with intravenous methylprednisolone pulse therapy and the clinical conditions gradually improved. After few months, patient symptoms progressed despite the addition of high-dose intravenous immunoglobulin, tacrolimus, and a new course of high dose steroids. To engage targeted therapy, the patient underwent brain biopsy that revealed a loss of myelin fibers, perivascular and diffuse infiltration of T cells, and macrophages associated with reactive gliosis, representing a demyelinating disease. We intensified treatment with cyclophosphamide and subsequently introduced ibrutinib as salvage strategy. Despite a magnetic resonance imaging showing great regression of the demyelinating lesions, patient’s conditions deteriorated and she died 16 months after HSCT.

Conclusions

CNS-GVHD is a rare complication of HSCT that is difficult to diagnose. Based on our experience, brain biopsy may represent a useful diagnostic tool when the clinical features of neurological symptoms are ambiguous or in patients without evidence of preceding chronic GVHD.

Keywords: allogeneic hematopoietic stem cell transplant (HSCT); steroid-refractory graft-versus-host disease (SR-GvHD); central nervous system (CNS); precision medicine; target therapy

Corresponding author: Sara Butera, Struttura Complessa di Ematologia a Direzione Universitaria, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy, E-mail: sara.butera@ospedale.al.it

Ethical approval: Not applicable.
Informed consent: Informed consent was obtained from all individuals included in this study.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.

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Received: 2023-08-16

Accepted: 2023-08-25

Published Online: 2023-10-17

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2023-0194

Keywords for this article

allogeneic hematopoietic stem cell transplant (HSCT); steroid-refractory graft-versus-host disease (SR-GvHD); central nervous system (CNS); precision medicine; target therapy