Central and peripheral nervous system immune mediated demyelinating disease after allogeneic hemopoietic stem cell transplantation for hematologic disease

Abstract

Immune mediated demyelinating disease (IMDD) after allogeneic hemopoietic stem cell transplant (HSCT) is rare and its etiology unclear. In this retrospective study, we identified patients who underwent HSCT between January 1992 and December 2010 and had IMDD post transplant. A total of 1,484 patients received HSCT and 7 (0.5 %) suffered from IMDD; five were men, and the median age was 54 years (range, 29-64 years). HSCT treated acute myeloid leukemia (n = 5), myelodysplastic syndrome (n = 1), and Waldenström macroglobulinemia (n = 1). All received an HLA matched donor graft, related (6), unrelated (1); from the bone marrow (1), peripheral blood stem cell (6); and T-cell depleted, ex vivo (6) or in vivo (1). The median time from transplant to neurologic symptoms was 120 days (range, 60-390 days). Three had acute demyelinating encephalomyelitis (ADEM), three acute inflammatory demyelinating polyradiculopathy (AIDP) and one autonomic neuropathy. Four of six patients tested had hemopoietic mixed chimerism prior to neurologic symptoms and low CD4(+) T-cell counts, median 76 (15-500 cells/μL). Two patients had simultaneous systemic graft versus host disease (GVHD). Two patients with ADEM had a spinal cord or brain biopsy which revealed demyelination. No patients had a viral etiology identified in the cerebrospinal fluid. Patients were treated with IV immunoglobulin, high dose steroids and/or rituximab. Five patients had a significant recovery. Response to immune modulators suggests an immune-based etiology. The incidence of de novo autoimmune disease after HSCT for hematological diseases is rare and may be difficult to differentiate from GVHD.

Bilateral Inflammatory Optic Neuropathy Related to Graft versus Host Disease Following Allogeneic Bone Marrow Transplantation for Hodgkin Disease

“…6,7 In these cases, treatment with steroids and immunosuppression led to neurological improvement and stabilisation in 3 of a series of 4 cases. 7 A recent study from Memorial Sloan Kettering 8 showed that of 1484 patients undergoing allogeneic stem cell transplants over an 18-year period, 7 developed neurological complications; 3 had ADEM and 4 had an inflammatory neuropathy. Those with ADEM each showed inflammation within the brain and spinal cord; biopsy in 2 cases showed demyelination with a heavy macrophage infiltration, although a less evident perivasculitis.…”

Late post-transplant anti-aquaporin-4 Ab-positive optic neuritis in a patient with AML

“…2 Allogeneic bone marrow transplantation (allo-BMT) after myeloablative conditioning is a current, effective treatment for many hematologic malignancies. In post-transplant patients, neurologic complications, which include posterior reversible encephalopathy, seizures, encephalopathy, polyneuropathy and central nervous system (CNS) infections, are described, but CNS immune-mediated demyelinating diseases (IMDD), either primary 4 or secondary to chronic GvHD, 5 are rare. We report on a patient who developed AQP-4-IgG-associated ON, after allo-BMT for AML.…”

“…The frequency of post-allo-BMT IMDD, which include ON, is rare, 0.5%, in the largest series of patients reported so far. 4 Six of the seven patients were transplanted from HLA-matched related donors, and the median time from transplant to the onset of neurologic symptoms was 4 months. 4 In another retrospective study on patients with severe autoimmune diseases, IMDD occurred up to 5 years after allo-BMT.…”

“…4 Six of the seven patients were transplanted from HLA-matched related donors, and the median time from transplant to the onset of neurologic symptoms was 4 months. 4 In another retrospective study on patients with severe autoimmune diseases, IMDD occurred up to 5 years after allo-BMT. 6 In our patient, the interval between allo-BMT and ON was 7 years.…”

“…This is the first case in the medical literature, as the previously reported allo-BMT cases with ON or NMOSD, which included longitudinally extensive transverse myelitis, were published in the pre-AQP-4-IgG era, or no information on such Ab testing was provided. 4,6 AQP-4-IgG positivity has prognostic meaning, as it predicts ON relapses, evolution to NMO and permanent neurological deficits.…”