Intense immunosuppression followed by autologous hematopoietic stem cell transplantation is significantly superior to mitoxantrone therapy in reducing the severity of multiple sclerosis (MS), according to a new study.
“This process appears to reset the immune system. With these results, we can speculate that stem cell treatment may profoundly affect the course of the disease,” said lead author Giovanni Mancardi, MD, of the University of Genoa in Italy.
More than 800 patients with MS have been treated worldwide with this procedure in recent years, usually within small phase I/II studies. Dr Mancardi and colleagues from the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation conducted a multicenter, phase II, randomized trial, including 21 patients, average age 36 years, with secondary progressive or relapsing-remitting MS. The patients had a documented increase in MS disability in the last year, despite receiving conventional therapy, and the presence of 1 or more gadolinium-enhancing (Gd+) areas.
The patients were randomized to receive intense immunosuppression followed by stem cell transplantation (9 patients) or mitoxantrone 20 mg every month for 6 months (12 patients). Completed MRI assessments were available in 17 patients.
With up to 4 years follow-up, intense immunosupression followed by stem cell transplantation reduced disease activity significantly more than mitoxantrone treatment. Those who received stem cell transplants had 79% fewer new areas of brain damage (T2 lesions) than those who received mitoxantrone; there were an average of 2.5 new T2 lesions for those receiving stem cells compared with 8 new T2 lesions for those receiving mitoxantrone. “This effect was already evident in the first year and was sustained through the 4-year follow-up,” the researchers stated.
Stem cell transplantation also resulted in a complete suppression of active inflammatory lesions, as demonstrated by the absence of new Gd+ lesions in the stem cell transplantation arm; inflammatory activity was still present in 56% of patients treated with mitoxantrone.
No difference was found in the progression of disability.
Dr Mancardi said that serious adverse effects that occurred with stem cell transplantation were expected and resolved without permanent consequences.
The researchers noted that mitoxantrone was given at a dose commonly used in Europe in rapidly worsening MS cases with MRI signs of inflammation, not the standard dosage of 12 mg/m2 every 3 months.
“More research is needed with larger numbers of patients who are randomized to receive either the stem cell transplant or an approved therapy,” Dr Mancardi said. “But it’s very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that is not responding well to standard treatments.”
The researchers speculate that stem cell transplantation may have a profound clinical impact for patients with MS who are still in the relapsing-remitting phase of disease.
Several phase III clinical trials are ongoing, including 1 that compares stem cell transplantation with the best approved therapy in severe MS cases, poorly responding to approved drugs, still in the relapsing-remitting phase of the disease, and showing clinical and MRI activity.
The researchers published their results in the February 11, 2015, online issue of Neurology.