Managing central nervous system manifestations of chronic graft versus host disease following hematopoietic stem cell transplantation: a case report.

Abstract Central nervous system (CNS) manifestation of chronic graft versus host disease (cGVHD) is a rare, difficult to diagnose phenomenon that can follow allogeneic hematopoietic stem cell transplantation (HSCT). CNS-cGVHD typically onsets 2-31 months post-transplant, involves diffuse infiltration of inflammatory cells, demyelination, and cerebral vasculitis, and is associated with an extremely poor prognosis. We present a case of a 37-year-old man who developed seizures, myopathy, bilateral upper and lower extremity weakness, confusion, and irritability almost 2 years after HSCT for acute myeloid leukemia (AML). CNS-cGVHD diagnosis was confidently determined via magnetic resonance imaging (MRI) demonstrating enhanced focal white matter lesions, cerebrospinal fluid (CSF) studies demonstrating elevated globulin (12.7 mg/dL; normal range: 0-6 mg/dL) and elevated immunoglobulin G (IgG) synthesis rate (13.9 mg/d; normal range: ≤ 8 mg/d), and a right brain biopsy demonstrating encephalitis, perivascular inflammation, microglial activation, and gliosis with predominately intramural and perivascular CD3+ T-cells, CD4+ and CD8+ cells. Complete resolution of neurological symptoms, including seizures, was achieved with a combination of steroids, ibrutinib, intravenous immunoglobulin (IVIG), and anti-seizure medications. Improvements to CNS-cGVHD was further indicated by normalized MRI studies without abnormal enhancements and improved CSF studies with reduction in globulin levels (11.3 mg/dL) and complete normalization of IgG synthesis rate (≤ 0 mg/d). It is imperative that CNS-cGVHD be considered in patients that present with neurological signs post-transplant. An early, confident diagnosis generates prompt intervention and as demonstrated, can lead to complete resolution of neurological symptoms.