When it comes to treating secondary-progressive multiple sclerosis (SPMS), a more advanced stage of the disease, little research has focused on autologous hematopoietic stem cell transplants (HSCT), which use healthy blood stem cells from a person’s own body (autologous) to replace diseased cells. New research published online in Neurology, the medical journal of the American Academy of Neurology, has found that people with active SPMS — meaning they continue to experience MS relapses or develop new lesions, as seen on their MRIs — who received stem-cell transplantation were slower in accumulating disability than those taking anti-inflammatory disease-modifying therapies (DMT). Most people with MS are first diagnosed with relapsing-remitting MS, marked by symptom flare-ups followed by periods of remission, but many people with relapsing-remitting MS eventually transition to secondary-progressive MS, which does not have wide swings in symptoms but rather a steady and slow worsening of the illness.
Study Shows Encouraging Results
“Our results are encouraging, because while current treatments for secondary-progressive MS have modest or small benefits, our study found stem cell transplants may not only delay disability longer than many other MS medications, but they may also provide a slight improvement in symptoms,” said study author Matilde Inglese, MD, PhD, of the University of Genoa in Italy and a professor of neurology, radiology, and neuroscience at Icahn School of Medicine at Mount Sinai in New York City, in a statement. The retrospective analysis involved 79 people with active secondary-progressive MS who received stem cell transplants and 1,975 people from the MS registry in Italy who were treated with MS drugs. Those in the medication group received anti-inflammatory disease-modifying therapies (DMT), such as beta-interferons (Avonex, Betaseron), azathioprine (Azason), glatiramer acetate (Copaxone, Glatopa), mitoxantrone (Novantrone), fingolimod (Gilenya), natalizumab (Tysabri), methotrexate (Rheumatrex), teriflunomide (Aubagio), cyclophosphamide (Cytoxan), dimethyl fumarate (Tecfidera), and alemtuzumab (Lemtrada).
Not Just Slowed Disability, but Improvement in EDSS Score
Disability in the study was measured with the Expanded Disability Status Scale (EDSS), which is a 10-point scale. A score of 6, for example, means a person needs to use a cane or brace intermittently or on one side to walk about 100 meters with or without resting. Scores of 6.5 are defined as needing to use a cane or brace constantly on both sides to walk about 20 meters without resting. Five years into the study, researchers discovered that 62 percent of those who had stem cell transplants experienced no worsening of their MS disability compared with 46 percent of those who took medications. At the five-year mark, people who received stem cell transplants were more likely to see sustained improvements over time, with 19 percent experiencing less disability than at study start compared with just 4 percent of people taking medications. At 10 years, the disability score for those who had received stem cell transplants decreased by an average of 0.01 points per year — meaning their disability improved. On the other hand, the average score for people taking medications increased by 0.16 points per year — meaning their disability worsened.
More, Larger Studies Needed to Confirm Benefits
“A proportion of patients with AHSCT [autologous hematopoietic stem cell transplants] had improvement in their disability scores, which further strengthens the argument that AHSCT is effective in secondary-progressive multiple sclerosis,” says Daniel Ontaneda, MD, of Cleveland Clinic’s Mellen Center for Multiple Sclerosis in Ohio. “However, all this data has to be taken with caution, as it is observational, and not produced in the gold standard context of a randomized clinical trial. Although the authors made attempts to ensure the groups were comparable, some residual confounding factors may still be present.” While the findings so far are encouraging, more research is needed in larger groups of people to confirm the findings, according to Dr. Inglese, who is also a member of the American Academy of Neurology. She added, “Results are not applicable to patients with secondary-progressive MS who do not have signs of inflammatory disease activity.” The study also did not include people taking the MS drugs siponimod (Mayzent), cladribine (Mavenclad), ocrelizumab (Ocrevus), ofatumumab (Kesimpta), or rituximab (Rituxan).
HSCT an Aggressive Form of MS Treatment
Christopher Lock, MD, a clinical associate professor of neurology and neurological sciences at Stanford University Medical Center in California, said that stem cell transplantation is an aggressive form of MS treatment and is not without risk, and is therefore usually considered only if other treatments are not working. “Stem cells are harvested by passing the blood through a machine which separates it into various components, and then the stem cells are collected,” says Dr. Lock, who was not involved in the research. “After the stem cells have been saved, the patient is then given strong chemotherapy medications which ‘ablate,’ or ‘knock out,’ the remaining bone marrow cells, including the autoreactive cells, which are thought to cause the damage to the myelin [insulating layer around nerves] in MS.” “The immune system is restored by giving the stem cells back — sort of like hitting the reset button,” adds Lock. The MS Society UK warns that chemotherapy can have some serious side effects, including hair loss, fever, nausea, and infertility. Risk of infections in the future also increases. If a person has already had a lot of nerve damage because of MS, the chemotherapy may do more harm than good. During recovery from the transplant treatment, patients may be vulnerable to infections and fevers.
HSCT Expensive and Time-Consuming, but Sometimes Very Effective
The transplant process is also expensive and takes time. The National MS Society estimates that the average total cost of care for inpatient AHSCT is $150,000, but costs vary across the United States. For insured patients, out-of-pocket spending for the procedure is generally far less. The Society also says that initial stem cell preparation and harvest takes 5 to 15 days, followed by a three-week hospital stay to prepare your immune system for the transplant, perform the stem cell transplant, and to allow recovery time. One of the major benefits of AHSCT is long-term control of MS. “It is clear that this is a long-acting therapy and may result in a decreased need for the more traditional immunomodulating medications used in MS,” says Dr. Ontaneda, who was not a study contributor. “However there are some patients who may have disease activity despite AHSCT. “Knowing in which patients AHSCT is only partially effective and how long the control of inflammation lasts is an ongoing area of research.”
