Central and peripheral nervous system immune-mediated demyelinating disease after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: We aimed to evaluate clinical and diagnostic features of central and peripheral immune-mediated demyelinating disease (CPID) in allogeneic hematopoietic stem cell transplantation (aHSCT) recipients.

BACKGROUND: CPID refers to the late-onset, immune-mediated neurological complications following aHSCT, when other frequent differential diagnoses have been ruled out, and when symptoms and signs of systemic GvHD manifestations are absent.

METHODS: Case records at the University of Tuebingen, between 2001 and 2015, were screened to identify patients with CPID after aHSCT.

RESULTS: Seven patients who developed CPID after aHSCT were identified. The average time interval from aHSCT until onset of CPID was 2.6 (±2.8) years (mean±SD). The most prevalent manifestations of CPID were optic neuritis and/or myelitis and polyneuropathy. Cerebrospinal fluid analyses involved elevated protein concentration and lymphocytic pleocytosis, while oligoclonal bands in CSF, but not in serum, were detected in 28% of cases. Aquaporin-4-antibodies were consistently absent. MRI studies showed features suggestive of demyelination processes, with cerebral and/or spinal cord white-matter involvement, and features compatible with cerebral vasculitis. Corticosteroids, Immunoglobulins, Cyclophosphamide, Rituximab and Interferon beta-1a showed marginal treatment responses, whereas plasma exchange resulted in marked clinical improvement in two treated patients. A chronic disease-course with persisting neurological deficits was prevalent.

CONCLUSIONS: CPID may comprise a rare complication of aHSCT, which manifests as optic neuritis and/or myelitis and is accompanied by sensorimotor polyneuropathy. A concomitant systemic manifestation of GvHD is not mandatory for CPID diagnosis. Usually, CPID exhibits a chronic, persisting disease course. Thus, clinical awareness is required, as early diagnosis and aggressive treatment may be prognostically advantageous.