Noninvasive tools based on immune biomarkers for the diagnosis of central nervous system graft-vs-host disease: Two case reports and a review of the literature

Abstract

BACKGROUND Central nervous system graft- vs -host disease (CNS-GVHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation. Currently, establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out. CASE SUMMARY Here, we present two patients with CNS-GVHD. Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes, and had abnormal cerebrospinal fluid (CSF) studies as determined by CSF and blood immune biomarker examinations, suggestive of suspected CNS-GVHD. Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients, we did not attempt to perform a brain biopsy, but prompted the initiation of empirical immunosuppressive therapy. In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings, a final diagnosis of CNS-GVHD was made. CONCLUSION CSF and blood immune biomarker examinations facilitated the diagnosis of CNS-GVHD, which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.

Monitoring Neurocognitive Functioning After Pediatric Cellular Therapy or Hematopoietic Cell Transplant: Guidelines From the COG Neurocognition in Cellular Therapies Task Force

“…Histology most frequently showed a lymphocytic vasculitis followed by microglial involvement [ 34 – 36 ]. Antibodies and immune biomarkers have been detected in a subset of patients [ 37 – 39 ]. Most responded to immunosuppressive treatment.…”

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System

“…Due to the rarity of CNS-GVHD and the difficulty to distinguish the disease from other mediators of CNS toxicity, biomarkers to identify CNS-GVHD would be highly desirable. IgG index in the CSF is an indicator of neurological disorders like multiple sclerosis, intrathecal inflammation ( 35 , 36 ). Another study indicated that Blood Brain Barrier (BBB) impermeability, IgG –Synthesis index are early indicators of CNS demyelination ( 37 ).…”

“…Another study indicated that Blood Brain Barrier (BBB) impermeability, IgG –Synthesis index are early indicators of CNS demyelination ( 37 ). In addition to this, increased BBB permeability, elevated myelin basic protein in blood and CSF are some of the immune markers that could be tested for their validity as biomarkers for CNS-GVHD ( 36 ). Identifying the immune biomarkers that predict damage to neurons, glial cells and myelin membranes may help diagnose CNS-GVHD.…”