Stem cell transplant reverses disabling MS-like disease

Summary: Hematopoietic stem cell transplantation reversed neuromyelitis optica. Five years following transplantation, only 2 of twelve patients had relapsed.

Source: Northwestern University

A stem cell transplant reversed a debilitating neurological disease that causes half of the patients to go blind and lose the ability to walk five years after diagnosis. Most of the patients stayed better five years after the transplant and were able to avoid drug treatment that cost up to $500,000 yearly, reports a new study from Northwestern Medicine and Mayo Clinic.

The disease is neuromyelitis optica, formerly classified as a rare subtype of multiple sclerosis (MS) but now considered a separate disease. Unlike MS and most other autoimmune disease, neuromyelitis optica has a biological marker, AQP4, that correlates with disease activity. After the stem cell transplant, patients no longer had discernable AQP4 in their blood.

“No prior therapy has caused AQP4 to consistently disappear or allowed patients to become treatment free,” said lead author Dr. Richard Burt, a professor of medicine and chief of immunotherapy and autoimmune disease at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician.

“There is marked difference between a transplant and the drug,” Burt said. “The transplant improved patients’ neurological disability and quality of life. They got better, and the disease maker disappeared for up to five years after transplant.”

The study was published Oct. 2 in Neurology.

Mayo Clinic in Rochester holds the patent for the biological marker AQP4 and did the biologic marker analysis in collaboration with Burt and Northwestern.

In the trial, 12 patients with neuromyelitis optica received the stem cell transplant.

“After five years, only two out of 12 relapsed and had to go back on drug therapy,” Burt said.

This is the fourth chronic disease hematopoietic stem cell transplantation (HSCT) has appeared to reverse.

The goal of HSCT is to reboot a faulty immune system. Hematopoietic stem cells are taken from the patient’s bone marrow or blood, then their immune stem is wiped out with chemotherapy. Next, their stem cells are reintroduced to the body where they migrate to the bone marrow, allowing their immune system to reset.

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This is the fourth chronic disease hematopoietic stem cell transplantation (HSCT) has appeared to reverse. The image is adapted from the Northwestern University news release.

Burt pioneered the field. He was the first to propose the approach of HSCT for MS in a medical publication, the first to do it in pre-clinical animal models and the first in America to treat MS patients with HSCT. Burt also conducted the first randomized HSCT trials for systemic sclerosis and multiple sclerosis, with strongly positive results.

In January 2019, Burt published a randomized study in JAMA showing HSCT reversed neurologic disability and then over 5 years slowed or in most patients prevented further progressive disability or evidence of new disease activity in relapsing-remitting multiple sclerosis. Other diseases HSCT has reversed, according to Burt’s published research, are systemic sclerosis and chronic inflammatory demyelinating polyneuropathy.

Additional Northwestern authors on the paper are Dr. Roumen Balabanov, Dr. Xiaoqiang Han, Carol Burns, Dr. Joseph Gastala, Borko Jovanovic and Irene Helenowski.

About this neuroscience research article

Northwestern University
Media Contacts:
Marla Paul – Northwestern University
Image Source:
The image is adapted from the Northwestern University news release.

Original Research: Closed access
“Autologous nonmyeloablative hematopoietic stem cell transplantation for neuromyelitis optica”. Richard K. Burt, Roumen Balabanov, Xiaoqiang Han, Carol Burns, Joseph Gastala, Borko Jovanovic, Irene Helenowski, Jiraporn Jitprapaikulsan, James P. Fryer, Sean J. Pittock.
Neurology doi:10.1212/WNL.0000000000008394.


Autologous nonmyeloablative hematopoietic stem cell transplantation for neuromyelitis optica

To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) could be a salvage therapy for neuromyelitis optica spectrum disorder (NMOSD).

Thirteen patients were enrolled in a prospective open-label cohort study (11 NMOSD aquaporin-4–immunoglobulin G [AQP4-IgG]–positive, 1 NMOSD without AQP4, and 1 NMOSD AQP4-IgG-positive with neuropsychiatric systemic lupus erythematosus [SLE]). Following stem cell mobilization with cyclophosphamide (2 g/m2) and filgrastim, patients were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day −5 to day −2, rATG (thymoglobulin) given IV at 0.5 mg/kg on day −5, 1 mg/kg on day −4, and 1.5 mg/kg on days −3, −2, and −1 (total dose 6 mg/kg), and rituximab 500 mg IV on days −6 and +1. Unselected peripheral blood stem cells were infused on day 0. AQP4-IgG antibody status was determined by Clinical Laboratory Improvement Amendments–validated ELISA or flow cytometry assays. Cell-killing activity was measured using a flow cytometry–based complement assay.

Median follow-up was 57 months. The patient with coexistent SLE died of complications of active lupus 10 months after HSCT. For the 12 patients with NMOSD without other active coexisting autoimmune diseases, 11 patients are more than 5 years post-transplant, and 80% are relapse-free off all immunosuppression (p < 0.001). At 1 and 5 years after HSCT, Expanded Disability Status Scale score improved from a baseline mean of 4.4 to 3.3 (p < 0.01) at 5 years. The Neurologic Rating Scale score improved after HSCT from a baseline mean of 69.5 to 85.7 at 5 years (p < 0.01). The Short Form–36 health survey for quality of life total score improved from mean 34.2 to 62.1 (p = 0.001) at 5 years. In the 11 patients whose baseline AQP4-IgG serostatus was positive, 9 patients became seronegative by the immunofluorescence or cell-binding assays available at the time; complement activating and cell-killing ability of patient serum was switched off in 6 of 7 patients with before and after HSCT testing. Two patients remained AQP4-IgG-seropositive (with persistent complement activating and cell-killing ability) and relapsed within 2 years of HSCT. No patient with seronegative conversion relapsed.

Prolonged drug-free remission with AQP4-IgG seroconversion to negative following nonmyeloablative autologous HSCT warrants further investigation.

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