What Is HSCT Treatment for Multiple Sclerosis?
Actress Selma Blair revealed on Instagram that she was undergoing HSCT treatment for multiple sclerosis, leaving many people wondering how the procedure works.
In July 2019, actress Selma Blair revealed on Instagram that she was undergoing hematopoietic stem cell transplantation (HSCT) to slow the progression of her multiple sclerosis (MS). The Cruel Intentions and Legally Blonde star first went public with her MS diagnosis in October 2018, after years of thinking she was experiencing minor ailments or a pinched nerve.
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Posing in her hospital room with a shaved head, next to an exercise bike, Blair wrote, “I am immunocompromised for the next three months at least, so no kisses please.” In later posts, she described the swelling, joint pain, and other side effects she was experiencing, saying “Chemo and other high dose drugs come at a price,” but “I am improving due to #HSCT.”
Blair’s candidness has many people asking, “What is HSCT?” Our experts answer that question and others.
How Does HSCT Work?
The “hematopoietic” in hematopoietic stem cell transplantation refers to blood cell–producing stem cells, which are extracted from the person’s own bone marrow or blood. To do the procedure, the doctors collect and store the stem cells to be transplanted after the rest of the patient’s immune cells are destroyed. That process is known as immuno-ablation. “The idea is to delete the malfunctioning immune system that produces the abnormal inflammation of MS and allow it to redevelop with the hope that it will no longer produce the autoimmune disease,” explains neurologist Jeffrey A. Cohen, MD, director of experimental therapeutics at the Mellen MS Center at the Cleveland Clinic.
While in the hospital the patient receives a powerful mix of chemotherapy drugs intravenously to wipe out the immune system. Once the cells are destroyed, the previously stored stem cells are re-infused intravenously to help rebuild a new immune system. Patients remain hospitalized for a minimum of 10 days—sometimes significantly longer. During this time, they are most at risk of bacterial, fungal, and viral infections as well as hemorrhage and other side effects. Over the next three to six months, the immune system gradually rebuilds itself.
How Effective Is It?
So far, results are promising, but the studies have been relatively small. In the first randomized controlled clinical trial, published in JAMA in January 2019, 110 patients, ages 18 to 55, with aggressive relapsing-remitting MS (RRMS)—at least two relapses while on disease-modifying therapy (DMT) in the prior year—were randomly assigned either to undergo HSCT or to receive a different type or stronger DMT than one they had taken the year before.
After one year, 103 people remained in the trial; only three of 52 people in the HSCT group experienced disease progression, compared with 34 of 51 people in the DMT group. Although progression did increase over time, significantly fewer progressed in the HSCT group compared to the DMT group. Patients in the drug therapy group had worsening scores on the Expanded Disability Status Scale (EDSS)—a measure of disability in patients with MS—while those in the HSCT group had improved scores. No deaths occurred in either group, and no one experienced disabling or potentially life-threatening events immediately following HSCT.
“All the damage from the disease may not go away, depending on the extent and how long people have had it,” says Richard Burt, MD, chief of immunotherapy and autoimmune diseases at Northwestern University Feinberg School of Medicine, the study’s lead author. “But I have patients now who have gone nearly 15 years without a relapse after this treatment.”
Which Chemotherapy Regimen Is Best?
The protocols for HSCT treatment, which use chemotherapy drugs approved by the US Food and Drug Administration, vary in intensity. The most common form used in the United States for HSCT is a combination of four chemotherapy drugs called BEAM, says Dr. Cohen. “BEAM is considered intermediate intensity compared to more aggressive myeloablative regimens—meaning they destroy bone marrow cells—that use either total body irradiation or high doses of busulfan, a chemotherapy drug. These more aggressive regimens are thought to be more effective, but they have more side effects so they are used less commonly, adds Dr. Cohen.
Dr. Burt uses a nonmyeloablative regimen that uses a less intense, lower-dose chemotherapy drug cyclophosphamide and doesn’t completely destroy bone marrow. “Our goal is to make the treatment effective while still as safe as possible. In theory, the more aggressive regimen is more effective, but I believe that more may not be better.”
Dr. Burt cautions, however, that no randomized trial has been done to compare non-myeloablative with more aggressive regimens.
Who Is Eligible?
The ideal patient for HSCT has highly active relapsing disease that has not responded adequately to the best available therapies, says Dr. Cohen. “HSCT is a major undertaking and has some safety issues. Even in the best of hands, current estimates of transplant-related mortality range between 0.2 percent and 0.3 percent.”
And unfortunately, it does not appear to be effective against the progressive form of MS. “When we first started studying HSCT in patients, the NIH advisory panel said that we had to start with patients who had progressive disease,” says Dr. Burt. “We did, and while it was fine safety-wise, it didn’t really help those people. We put ‘failure’ in the title of the publication, because we wanted everyone to understand not to do this in progressive MS. There is a tendency among some neurologists to give a patient all the available DMTs, and when they have progressive disease, offer a transplant—but it won’t help at that point.”
In addition to the risk of infection, patients who undergo HSCT also have an increased risk of developing cancer or other autoimmune conditions, such as thyroiditis. Early menopause and fertility problems are also a possibility, so Dr. Burt advises his patients who may still want to bear children to undergo egg preservation before starting treatment.
What’s in the Pipeline?
Two additional randomized clinical trials are about to begin. BEAT-MS, led by Dr. Cohen, will compare a transplant using one chemotherapy regimen to the best currently available disease-modifying therapies. RAM-MS, led by Haukeland Hospital in Norway, will compare Dr. Burt’s chemotherapy regimen with disease-modifying therapy using alemtuzumab.
“I do not use the word ‘cure’ because only time can answer that question for MS. And while this treatment could be considered for RRMS with frequent relapses, it is not for all patients with MS,” Dr. Burt says. “But many people who undergo this treatment have very durable results and can go off all their other drugs. It can fundamentally change the natural history of this disease.”
Where Should Patients Undergo HSCT?
Like HSCT for cancer, HSCT for MS does not require approval by the US Food and Drug Administration because the stem cells are not a drug but instead a supportive blood product. “However, this procedure should be performed in clinical trials, either at experienced centers or new centers willing to invest the time and dedication to establish expertise.” Dr. Burt, who is taking a planned research sabbatical, is still treating patients who were previously evaluated and approved for the procedure, but he’s not accepting new patients, and the clinic at Northwestern will close in his absence.
