University of Calgary
Medicine

Author Of 1 Presentation

Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0691 - Autologous Hematopoietic Stem Cell Transplantation in Neuromyelitis Optica – Year 5 Update (ID 1042)

Speakers
Presentation Number
P0691
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis Optica Spectrum Disorder (NMO/NMOSD) is an immune astrocytopathy characterized by disabling attacks of optic nerves, spine, the area postrema, hypothalamus and other CNS regions. Although new, targeted therapies have recently been approved, they require indefinite use, with data limited essentially to positive aquaporin-4 (AQP4) patients. As well, many patients may not have access to such agents and still rely on older, harsher immunosuppressants. The immunological features of NMO/NMOSD, coupled with its severity, make it an ideal candidate for trials of autologous hematopoietic stem cell transplantation (AHSCT), with the goal of disease remission and freedom from long-term treatment. Several small studies, with a variety of transplant regimens, have been presented thus far, with mixed results.

Objectives

To determine if NMO/NMOSD patients who have failed standard immune maintenance therapy, experience a reduction in relapse and disability without need for immune therapy after AHSCT.

Methods

Starting in 2010, patients were eligible and enrolled if they met Wingerchuk 2006 criteria for NMO, aged 18-65, with => 1 relapse in 12 months or => 2 in 24 months despite immunotherapy and EDSS < 6.5. Patients underwent non-ablative stem cell mobilization and infusion using cyclophosphamide (200mg/kg - divided as 50mg/kg/day over days -5 to -2), ATG and rituximab. The primary endpoint was a 50% reduction in relapse rate at year 3 (secondary at year 5). Additional outcomes included annualized relapse rate (ARR), EDSS, MRI, AQP4 serostatus, and optical coherence tomography over 5 years. Ten subjects were to be enrolled to provide 80% power.

Results

Between 2010-2015, 3 patients were enrolled and underwent AHSCT. A 28F, AQP4-, was transplanted in 2011. Her ARR dropped from 5 to 0 at both year 3 and 5, with her EDSS dropping from 4.0 to 2.0. A 36F, AQP4+, transplanted in 2012, had a reduction in her ARR from 4 to 0.67 at year 3, and 0.5 at year 5, with her EDSS dropping from 4.5 to 3.0 throughout the trial. She was treated with MMF after her two mild post-transplant relapses. The final patient, a 39M, AQP4+ was transplanted in 2014. He had a precipitous decline with an ARR increasing from 1.3 to 2 at year 3 and 5, and an EDSS increasing from 3.5 to 7.5 at year 3, with death from NMO at year 3.5. As well, both seropositive patients remained seropositive after transplant. The trial was closed in 2016 due to challenges in recruitment.

Conclusions

While the small cohort size limits interpretation, two of three patients had a marked improvement in their NMO activity and disability after AHSCT. Regimen selection and patient features may speak to the success and failures in this trial and other published studies, but it appears that AHSCT in NMO/NMOSD is a viable option worthy of further study and refinement.

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