Late Relapse After Prolonged Remission Post-autologous Hematopoietic Stem Cell Transplantation in Two Patients with AQP4-IgG+ Neuromyelitis Optica Spectrum Disorder
Nisa Vorasoot1, Kyle Blackburn4, Jiraporn Jitprapaikulsan5, Melissa Bush2, James Fryer3, Sean Pittock1
1Neurology, 2Center of MS and Autoimmune Neurology, 3Laboratory Medicine and Pathology, Mayo Clinic, 4Neurology, University of Texas Southwestern Medical Center, 5Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
Objective:

To report the long-term outcomes of two NMOSD patients post-transplant from the previous report.

Background:

A previous study on non-myeloablative autologous hematopoietic stem cell transplantation (AHSCT) in patients with neuromyelitis optica spectrum disorder (NMOSD) reported seroreversion from AQP4-IgG + to - status and up to five years of remission [Neurology. 2019;93(18):e1732-e1741]. Longitudinal follow-up data beyond five years are lacking, and patients may become lost to follow-up.

 

Design/Methods:

We conducted clinical record reviews and measured AQP4-IgG status and cell-killing activity using live AQP4-transfected cells by flow cytometry.

Results:

The first patient, a 73-year-old woman diagnosed with NMOSD in January 2010 after presenting with longitudinal extensive transverse myelitis (LETM) and testing positive for AQP4-IgG (titer 100), experienced a LETM relapse in April 2010. After AHSCT in October 2010, her AQP4-IgG seroreverted to negative status, and she remained relapse-free for 12 years. However, she later relapsed with area postrema syndrome, and her AQP4-IgG seroconverted to positive (titer 1000). She made a good recovery following steroid treatment and commenced Eculizumab. The second patient, a 60-year-old woman, experienced multiple episodes of optic neuritis dating back to November 2002, with an AQP4-IgG titer of 1:100 in 2008. Despite receiving rituximab, she had relapses of LETM from 2010-2012. After AHSCT in February 2013, her AQP4-IgG seroreverted to negative status, and she remained relapse-free for 10 years. However, she later relapsed with LETM, and her AQP4-IgG seroconverted to positive (titer >100,000). Unfortunately, she developed pulmonary aspergillosis and passed away in September 2023.

Conclusions:

Patients undergoing AHSCT for AQP4+ NMOSD who experience seroreversion (+ to - AQP4-IgG status) and remain attack-free for 10 years or more may eventually seroconvert (- to +) and relapse. This study highlights the necessity for continued clinical and serological surveillance over the long term in NMOSD patients post-AHSCT.

10.1212/WNL.0000000000204806