Recommendations Published for Stem Cell Transplant in Multiple Sclerosis


The authors noted that research is still needed to establish standards for cell mobilization and immune-conditioning regimens.

Aaron Miller, MD

Aaron Miller, MD

The National Medical Advisory Committee of the National Multiple Sclerosis Society have published recommendations on the use of autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis (MS) based on current research, pointing out areas of continued controversy and issues requiring further research.

The committee concluded that AHSCT may be a useful treatment option for patients with relapsing MS who demonstrate substantial breakthrough disease activity despite treatment with high-efficacy disease-modifying therapy (DMT) or who have contraindications to high-efficacy DMTs. 

The authors, led by Aaron Miller, MD, medical director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis and professor of neurology, Icahn School of Medicine at Mount Sinai, concluded that the procedure is best suited for people younger than 50 years of age with shorter disease duration (<10 years). In addition, the procedure should only be performed at centers with substantial experience and expertise.

Appropriate Candidates for AHSCT

The recommendations note that previous research studies have concluded that the likelihood of benefit from AHSCT is much smaller for patients with progressive MS without recent disease activity. As well, patients who are older and have greater disability have a greater risk for serious complications or death associated with the procedure.

A report from the International Conference on Cell-Based Therapies for Multiple Sclerosis concluded that the benefit from immunoablation followed by AHSCT (I/AHSCT) is most significant in those who have accumulating disability but are still ambulatory and have ongoing disease activity despite DMT.

There are still questions regarding how long disease duration should be, how much disease activity an appropriate candidate should have, if clinical activity should be required, and whether a patient presenting with very active disease should turn to AHSCT as a first-line therapy, among others. Despite the lack of concrete data to answer these questions, Miller and colleagues concluded that guidance can be taken from the inclusion and exclusion criteria from the Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS; NCT04047628) randomized clinical trial that recently began and will compare AHSCT with highly efficacious DMT. 

Candidates for that trial are between 18 and 55 years of age, are ambulatory without aids, and have “highly active, treatment-resistant relapsing MS.” The last requirement is defined as 2 or more episodes of treatment failure in the 24 months prior to screening. The authors also noted that patients considering AHSCT should think about participating in a randomized clinical trial, if possible.

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Optimal Treatment Location

The authors noted that only few centers offer the adequate amount of expertise and quality assurance oversight to perform AHSCT. In addition to needing accreditation, centers performing AHSCT for MS should have transplant teams that include not only hematologist-oncologists with extensive experience in AHSCT, but also neurologists with expertise in MS diagnosis and treatment. 

AHSCT accrediting agencies such as the Foundation for the Accreditation of Cellular Therapies (FACT), Joint Accreditation Committee of the International Society for Cellular Therapy and Europe (JACIE) and the European Society for Blood and Marrow Transplantation recently embarked on a joint effort to improve this process. The results of the group’s work will help establish standardized outcome measures, increase accountability, and allow meaningful comparisons across centers performing AHSCT. 

Protocol for AHSCT in People With MS

While protocols differ significantly among centers, all protocols use a mobilization stage to stimulate release of precursor cells into the blood for harvesting and subsequent preservation. These mobilization protocols involve the use of granulocyte-colony stimulating factor to stimulate cell proliferation. Once sufficient cells have been separated from the blood and preserved, patients are given a conditioning regimen designed to kill current immune cells. 

“Proponents of higher-intensity regimens, such as those including busulfan, argue for increased efficacy with the more intensive regimens, with higher rates of effective MS disease activity suppression and longer durability of benefit, albeit at the cost of increased risk of infections and other complications, including potential mortality,” Miller and colleagues concluded. “Proponents of the nonmyeloablative, lower-intensity regimens maintain that their approach produces high efficacy with less risk of complications.”

They added that optimal conditioning regimen depends on balancing expected efficacy with the safety of the procedure in the population of patients with MS for whom it will be used. Notably, the concluded that it is possible that optimal regimens may differ in different patients with MS, although no basis for selecting among them based on individual patient characteristics currently exists. 

Treatment Course and Follow-up

The recommendations also covered the process of AHSCT mobilization and leukapheresis and harvest, which takes between 5 to 15 days and is followed by an ablation regiment and then transplant of the autologous stem cell graft. Patients are generally admitted to the hospital for 3 weeks for the ablation and transplantation regimen, as well as recovery. 

Miller and co. proposed that neurologic evaluations should take place within 2 weeks after discharge and every 2 to 4 months following. Cognitive evaluation should occur at baseline and within 1 year of AHSCT. Medical evaluation should be recommended immediately following transplant and every 2 to 3 months for 2 years by a hematologist or internist, per the committee.

A magnetic resonance imaging (MRI) of the brain or spine should be obtained within 6 months after discharge, and then at minimum annually, to evaluate for new lesion formulation and brain volume changes. Serum evaluations should be performed at discharge and then every 4 weeks for 1 year. Psychological and supportive care should be offered during hospitalization and/or at discharge, and patients should be followed every 1 to 2 months or as needed. 

The authors noted that it is appropriate to weigh the costs between AHSCT and pharmacotherapy when considering treatment options. The estimated cost for AHSCT is approximately $150,000 for one time treatment compared to treatment with DMTs which entails a mean annual price of $80,000 or more, continuing indefinitely. 

Miller AE. Chitnis T, Cohen BA, Costello K, Sicotte NL, Stacom R. Autologous hematopoietic stem cell transplant in multiple sclerosis. JAMA Neurol. Published online October 26, 2020. doi: 10.1001/jamaneurol.2020.4025
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