Neurological manifestations of chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease

Abstract

A major obstacle of allogeneic haematopoietic stem cell transplantation is graft-versus-host disease, an immune-mediated disorder that affects multiple tissues and organs with varying severity. Neurological complications of acute and chronic graft-versus-host disease are rare but can produce severe clinical problems with significant morbidity and mortality. In this article, we review neurological manifestations of chronic graft-versus-host disease that comprise immune-mediated neuropathies, myasthenia gravis and myositis in the peripheral nervous system and various cerebrovascular complications, demyelination and immune-mediated encephalitis in the central nervous system. The National Institutes of Health consensus on criteria for clinical trials in chronic graft-versus-host disease recommended that the diagnosis of chronic graft-versus-host disease of the nervous system can be made only when other organs are affected by graft-versus-host disease and frequent neurological differential diagnoses such as drug-induced toxicities or opportunistic infections are excluded. The Consensus Conference on Clinical Practice in chronic graft-versus-host disease, held in autumn 2009 in Regensburg, aimed to summarize the literature and to provide guidelines for the diagnostic approach in children and adults with neurological manifestations of chronic graft-versus-host disease. Moreover, we present therapeutic recommendations and their level of evidence for the management of these complications. Overlapping symptoms and comorbidities after allogeneic haematopoietic stem cell transplantation and the limited knowledge about the underlying biological mechanisms of chronic graft-versus-host disease affecting the nervous system emphasize the need for further experimental and clinical investigations.

Clinical Reasoning: A 45-year-old man with acute onset of multifocal weakness and paresthesias

“…Neurologic manifestations of GVHD can result from involvement of the CNS (encephalitis, myelitis) or the PNS (acute or chronic demyelinating neuropathy, myositis). 1 Our patient's neurologic symptoms were thought to be due to an immune-mediated neuropathy, another complication of his GVHD. Other conditions like herpes zoster and vasculitic neuropathy were considered to be improbable based on the appearance of the rash and lack of pain.…”

Graft versus self (GvS) against T-cell autoantigens is a mechanism of graft–host interaction

“…Two patients (7,9) showed T-cell responses directed against self-peptides, whereas in samples of two other patients (12,23), T cells recognized both self-and non-self-peptides. In two patients (11,20), T-cell responses could not be further discriminated. Of note, none of the observed T-cell responses was associated with a defined genetic polymorphism.…”

“…Because GVHD of the CNS is difficult to distinguish from other complications such as relapse, infections, and toxicity related to therapy, a thorough characterization of CNS GVHD is challenging (7,11).…”

Erratum: Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection

“…25 There are also reports of central nervous system involvement of chronic graft versus host disease following allogenic hematopoietic stem cell transplantation, with manifestations including stroke-like episodes, seizures, encephalopathy, myelopathy, optic neuritis, and other focal neurologic deficits. 26 In the United States, the Food and Drug Administration (FDA) regulates stem cells to ensure that they are safe and effective for their intended use. Mesenchymal stem cells that come from bone marrow or blood are routinely used in transplant procedures to treat patients with cancer and other disorders of the blood and immune system.…”