New, high risk stem cell transplant method might provide long-term MS relief
A new clinical trial shows how an intensive procedure that completely wipes out the immune system and regenerates a new one with the help of blood stem cells can significantly reduce inflammation in patients with early, aggressive multiple sclerosis (MS) and lead to lasting recovery. The trial involved 24 participants who were followed for up to 13 years and is the first to show a complete, long-term suppression of inflammation in patients with MS.
However, treatment-related risks limit its widespread use.
MS is among the most common chronic inflammatory diseases of the central nervous system, with around 2 million people affected worldwide. It is caused when the immune system attacks the body, known as autoimmunity. Some specialist centers offer autologous hematopoietic stem cell transplantation (aHSCT) for MS, which involves harvesting bone marrow stem cells from the patient, using chemotherapy to suppress the patient’s immune system and reintroducing the stem cells into the blood stream to “reset” the immune system to stop it attacking the body. However, many patients relapse after these treatments, so more reliable and effective methods are needed.
Harold L. Atkins, M.D., and Mark S. Freedman, M.D., from Ottawa Hospital and the University of Ottawa, Ottawa, Canada, and colleagues tested whether complete destruction, rather than suppression, of the immune system during aHSCT would reduce the relapse rate in patients and increase long-term disease remission. They enrolled 24 patients aged 18-50 who had all previously undergone standard immunosuppressive therapy that did not control the MS. All patients had poor prognosis and their disability ranged from moderate to requiring a walking aid to walk 100 meters, according to their Expanded Disability Status Scale (EDSS) scores.
The researchers used a method of aHSCT similar to what is currently used, but instead of only suppressing the immune system before transplantation, they destroyed it completely using a chemotherapy regimen. Dr. Atkins explained that this treatment is “similar to that used in other trials, except our protocol uses stronger chemotherapy and removes immune cells from the stem cell graft product. The chemotherapy we use is very effective at crossing the blood-brain barrier and this could help eliminate the damaging immune cells from the central nervous system.”
The primary outcome of the study, published in The Lancet, was MS activity-free survival at three years, which occurred in 69.6% of patients after transplantation.
Out of the 24 patients, one died from hepatic necrosis and sepsis caused by the chemotherapy. Prior to the treatment, patients experienced 1.2 relapses per year on average. After treatment, no relapses occurred during the follow-up period (between four and 13 years) in the surviving 23 patients. These clinical outcomes were mirrored by freedom from detectable new disease activity on MRI images taken after the treatment. The initial 24 MRI scans revealed 93 brain lesions, and after the treatment only one of the 327 scans showed a new lesion.
Furthermore, progressive brain deterioration typical of MS slowed to a rate associated with normal aging in nine patients with the longest follow-up, and eight of 23 patients had a sustained improvement in their EDSS score at 7.5 years after treatment. At three years, six patients were able to reduce or stop receiving disability insurance and return to work or school. Eight of the 24 patients had a moderate toxic effect and 14 patients had only a mild toxic effect related to transplantation.
Dr. Freedman said the results should be interpreted with caution. “The sample size of 24 patients is very small, and no control group was used for comparison with the treatment group,” he explained. “Larger clinical trials will be important to confirm these results. Since this is an aggressive treatment, the potential benefits should be weighed against the risks of serious complications associated with aHSCT, and this treatment should only be offered in specialist centers experienced both in multiple sclerosis treatment and stem cell therapy, or as part of a clinical trial. Future research will be directed at reducing the risks of this treatment as well as understanding which patients would best benefit from the treatment.”