Long-term remission of neuromyelitis optica with allogeneic hematopoietic stem cell transplant

Neuromyelitis optica (NMO) is a rare, aggressive, neurological autoimmune disorder. Despite several immunosuppressive drugs having been recently approved, some patients still experience frequent relapses, leading to disability accrual.

We report the long-term follow-up of the two patients treated with allogeneic hematopoietic cell transplantation (alloHCT) for treatment-refractory anti-aquaporin-4 immunoglobulin G (AQP4-IgG)-positive NMO 16 and 15 years ago, respectively. Patients were followed with serial clinical, imaging, and immunological assessments.

Both patients showed sustained clinical and radiological remission without ongoing immunosuppressive therapy. AQP4-IgG antibodies became undetectable after transplantation and remained so throughout follow-up. No graft-versus-host disease occurred, and full donor chimerism was maintained. Longitudinal immune profiling revealed robust reconstitution of naive and memory T and B cell compartments, a resting phenotype in polyclonal T cells, and dynamic remodeling of regulatory T cells.

AlloHCT induced durable, treatment-free remission over more than 15 years in two patients with highly refractory NMO spectrum disorder (NMOSD), accompanied by sustained clearance of pathogenic AQP4-IgG antibodies. This long-term disease control paralleled stable donor-derived immune reconstitution, notably with expansion and remodeling of regulatory T cells, providing a rationale for hypothesizing a mechanistic link to immune tolerance. These findings provide proof of concept that alloHCT can achieve deep, potentially curative disease modification in selected NMO cases, warranting further studies to better define patient selection, safety, and long-term benefit.

No funding was received for this work.