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Stem cell therapy for MS: Which patients is it right for?

By Jim Kling

credit: Philippe Garo / Science Source

Autologous hematopoietic stem cell transplant (AHSCT) shows promise for the treatment of relapsing multiple sclerosis (MS), but prospective clinical trials need to be done to confirm findings. The treatment could best be applied to patients aged under 50 years with disease duration less than 10 years, who are ineligible for disease-modifying therapies, or who have breakthrough symptoms with these treatments, such as clinical relapses or new inflammatory central nervous system lesions.


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Those are the highlights of new recommendations from the National Multiple Sclerosis Society, published in the February issue of JAMA Neurology.

AHSCT is one of several cell-based therapies for MS, but it has the most evidence supporting its efficacy. In a treatment regimen, stem cells are first collected from the patient, who then undergoes depletion of his or her own immune cells, including the self-reactive cells that lead to disease. The previously extracted stem cells are then returned to replenish the immune system with the hope that it will be less self-reactive. Researchers are unsure how much of the efficacy comes from the initial reduction of the immune system, and how much from the reinfused stem cells, which may inhibit self-reacting immune cells.

The procedure is recommended for patients aged younger than 50 years in comparatively good health because “this is a rather heroic therapy. The reason it works is that you’re ablating the existing immune response, kind of resetting the thermostat. You’re at significant risk of infections during that period when you’re immune system is basically out of function. When you are older and more debilitated, your risk of the procedure probably goes up,” said Aaron Miller, MD, who chaired the committee that created the recommendations. He is the medical director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Icahn School of Medicine at Mount Sinai, New York.

The good news is that mortality has improved over time, from 2.0% between 1995 and 2016 to 0.2% between 2012 and 2016. Serious adverse events, which typically occur during the initial ablation of the immune system, have also come down. Some of that improvement is likely attributable to better patient selection.

Dr. Aaron Miller

credit: Molecule Medical Arts / Science Source

The arduous procedure results in significant short-term risk of infection, but successfully treated patients can stop taking immunosuppressive drugs, which carry an ongoing risk of infection. “You’re taking an up-front risk for the sake of a long-term benefit,” said Dr. Miller.

AHSCT should be limited to patients who have had breakthrough symptoms (new inflammatory central nervous system lesions and/or clinical relapses) despite highly effective disease-modifying therapies. It should not be considered for patients who are experiencing gradually progressing disease, because that clinical course is likely caused by different biological mechanisms which are less likely to be helped by AHSCT, according to Dr. Miller.

Moreover, researchers haven’t yet determined if the approach is superior to effective disease-modifying drugs because the relative safety of transplant, compared with the risks of long-term medication use is not yet understood. There is a clinical trial in progress called Beat MS, which researchers hope will answer that question. Patients who have breakthrough activity on usually effective disease-modifying drugs are being randomized to another highly efficacious disease-modifying drug or AHSCT. However, results of this trial are likely years away.

Those considering the procedure should seek out a highly reputable transplant center, The National Multiple Sclerosis Society recommends that AHSCT should only occur at centers with experience and expertise in both MS care and stem cell transplant. Patients choosing to undergo the procedure should also consider joining a clinical trial, if possible. That will ensure quality of care and an acceptable protocol, as well as contributing to efforts to answer key clinical questions.

Further, the National Multiple Sclerosis Society believes that:

  • People with MStreated with AHSCT should be entered into a single database for long-term follow-up.
  • Research is needed to establish standards for cell mobilization and immune-conditioning regimens.
  • Continuing research on comparative effectiveness of AHSCT and high-efficacy DMT is needed.

Dr. Miller has no relevant financial disclosures.