Stem-cell transplant keeps rare autoimmune disease in remission for 15 years

Two patients with neuromyelitis optica spectrum disorder stayed in remission for more than 15 years after an allogeneic hematopoietic stem-cell transplant, a result that pushes autoimmune medicine toward a harder question: how deep can an immune reset really go? The paper, published online June 15 in Med by investigators at IRCCS San Raffaele Scientific Institute in Milano, is striking precisely because it is so small. It is not a cure on the strength of two cases, but it is one of the longest remissions reported in a disease that can leave patients severely disabled after a relapse.

NMOSD is often driven by pathogenic antibodies against aquaporin-4, and attacks can target the optic nerves and spinal cord. Without treatment, up to one-half of patients may develop severe disability, including blindness or paralysis, within five years. That threat gives unusual weight to any treatment that can keep the disease quiet for years, especially when the procedure is as intense as hematopoietic stem-cell transplantation. The San Raffaele paper includes Giorgio Orofino, Angela Genchi, Paolo A. Muraro, Fabio Ciceri, Massimo Filippi, Lucia Moiola and Raffaella Greco among its authors.

The new report also lands in a field that has learned to be cautious. A 2025 case series in JAMA Network Open described two AQP4-IgG-positive patients who remained attack-free for at least five years after autologous hematopoietic stem-cell transplantation before relapsing more than 10 years later. That history matters: an early response can look like victory long before the immune system proves otherwise. Against that backdrop, 15-year remission is exceptional, but not proof that the approach will generalize.

Earlier experience points in the same direction, while still underscoring the limits. A 2019 Mayo Clinic cohort enrolled 13 patients and had a median follow-up of 57 months. Among the 12 NMOSD patients without other active coexisting autoimmune disease, 11 were more than five years past transplant and 80% were relapse-free off all immunosuppression. Disability improved, with Expanded Disability Status Scale scores falling from 4.4 at baseline to 3.3 at five years, and quality of life rose sharply, with SF-36 total scores increasing from 34.2 to 62.1.

The treatment landscape has also changed. Reviews describe older NMOSD care as depending on off-label azathioprine, mycophenolate mofetil and cyclophosphamide, while newer options now include satralizumab, inebilizumab, eculizumab and ravulizumab. An ECTRIMS-EBMT consensus statement says autologous hematopoietic stem-cell transplantation can be a treatment option for some patients, but its place in the therapeutic algorithm remains uncertain. That is the real takeaway from the San Raffaele cases: for selected patients with severe, relapse-prone disease, stem-cell transplant may point to a durable new frontier, but the field still needs larger studies, better markers and longer follow-up before anyone can call it finished.