People with relapsing forms of multiple sclerosis (MS) are usually prescribed disease-modifying medications to reduce attacks and slow the disease course from worsening. While these medications have been proven effective, a new clinical trial has found that a blood stem cell transplant may produce better, longer-lasting outcomes.
“The simple way to say it is the transplant gave superior results to the drugs,” says lead study author Richard Burt, MD, chief of the division of immunotherapy and autoimmune diseases at Northwestern University’s Feinberg School of Medicine in Chicago.
As reported in the January 15 edition of The Journal of the American Medical Association, Dr. Burt and collaborators conducted the first randomized trial comparing disease-modifying drug therapy (DMT) with hematopoietic stem cell transplantation (HSCT). Hematopoietic stem cells develop into all different types of blood cells, including white blood cells, which are a part of the immune system.
The investigation included 110 patients with highly active relapsing-remitting MS. About 80 to 85 percent of MS patients are first diagnosed with relapsing-remitting MS, which is characterized by stable periods interrupted by flare-ups, or exacerbations, during which existing symptoms, such as problems with balance or vision problems, worsen and new symptoms sometimes appear.
Half the study participants were randomly selected for transplant (which is a one-time treatment), while the remainder received disease-modifying medications. Subjects, who had an average age of 36, had experienced at least two relapses while taking medication the year before starting the study.
Significant Improvements in Stem Cell Transplant Group
After a follow-up of up to five years, MS symptoms had worsened in three people who had received HSCT, compared with 34 who had disease-modifying drug therapy. The average time to disease progression was two years in the medication group, but the transplant group had too few events to calculate progression.
When it came to measures of disability (on the Expanded Disability Status Scale, or EDSS), transplant patients showed improvement, while medication patients declined.
Burt pointed out that the lesion burden in the brain (which indicates nerve cell damage) grew for those taking medications (increasing 33 percent) versus those who received the stem cell procedure (decreasing 33 percent).
He also remarked that transplant patients had a noticeable improvement in quality of life, whereas quality of life did not improve in the drug group.
“It makes sense that your quality of life goes up if you have a one-time stem cell treatment and you’re off all drugs and getting better,” says Burt. “Whereas on drugs, you just stay on drugs until you have too bad of a side effect or your disease progresses or you have too many relapses. Then doctors give you a new drug.”
‘Rebooting’ the Immune System With HSCT
Hematopoietic stem cell transplantation is most often performed in people with specific cancers, such as multiple myeloma and leukemia. When it comes to multiple sclerosis, the treatment is still in its infancy, according to the National Multiple Sclerosis Society (NMSS).
In addition to this recent study, other research has shown this blood stem cell procedure to be beneficial for individuals who have highly inflammatory relapsing-remitting MS, according to the NMSS. Clinical trials are still ongoing to determine the effectiveness and safety of HSCT, but some centers, such as the Fred Hutchinson Cancer Research Center in Seattle and Northwestern University in Chicago, provide the treatment for people with multiple sclerosis.
The NMSS says that the idea behind the HSCT is to “reboot” the immune system to stop its attack on the brain and nervous system. Doctors first collect stem cells from the blood. After treatment with immune-specific chemotherapy and an antibody to suppress or kill immune cells in the person with MS, the stored stem cells are infused into the bloodstream through a vein.
Burt estimates that the average time required in the hospital for the procedure is 15 days.
The transplantation can pose risks, such as infection and even death. Burt says that this trial used a “very light” immune-specific chemotherapy regimen that was less toxic than those used in some other investigations. The study authors reported few adverse effects and no deaths.
“This is very powerful therapy, but it can be very safe,” says Burt.
Limitations to the Study
The researchers recognized several study limitations, including the small number of participants and allowing patients in the DMT group who failed to respond to treatment to cross over to receive HSCT.
Asaff Harel, MD, a neurologist at Lenox Hill Hospital in New York City who was not involved in the study, noted that the rates of relapses and disability worsening in the DMT group seem high compared with other similar studies.
“The high number of relapses and disease worsening on Tysabri (natalizumab), a highly effective medication, raises some questions,” he says.
Study a First Step in Refining a Promising Treatment
As far as future research, Burt would like to follow more patients for a longer period to determine outcomes at 10 years, 15 years, and beyond.
“I do have some patients between 10 and 15 years, though, who have never relapsed and never had any new disease activity on MRI,” says Burt.
He adds that this type of long-lasting, one-time treatment could mean substantial cost savings for patients and insurance companies. Although the price for transplant can be high, it could be cost-effective in the long run compared with taking MS medications, which can cost tens of thousands of dollars a year.
“This study is a first step,” says Burt. “Just as the Wright brothers’ first airplane went 120 feet but now you have jets flying nonstop around the world, this treatment shows promise so far, but I think it can be refined and advanced over time.”