Transplanting a patient’s own hematopoietic stem cells may defer the progression of disability longer in patients with secondary progressive multiple sclerosis (SPMS) than treatment with other anti-inflammatory disease-modifying therapies (DMT), reports a study published in the journal Neurology “Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis”.

“Hematopoietic stem cell transplants have been previously found to delay disability in people with relapsing-remitting MS, but less is known about whether such transplants could help delay disability during the more advanced stage of the disease,” said Matilde Inglese, MD, PhD, professor of neurology at the University of Genoa in Italy and senior author of the study. “Our results are encouraging because while current treatments for SPMS have modest or small benefits, our study found stem cell transplants may not only delay disability longer than many other MS medications, they may also provide a slight improvement in symptoms.”

Patients initially diagnosed with relapsing-remitting MS, where periods of active flare-up of symptoms alternate spans of remission, eventually develop SPMS where the disease worsens gradually but steadily. The exact mechanisms leading to increased neurodegeneration in SPMS are unclear, but evidence suggests a major role of innate and adaptive immune mechanisms that drive inflammation in the brain parenchyma, the leptomeninges, and the cerebrospinal fluid.

Earlier studies have suggested that the use of anti-inflammatory medications such as siponimod may be therapeutically beneficial in SPMS. However, DMTs reduce the overall risk of disability only modestly and the duration of their effects are unclear. On the other hand, AHSCT resets immune dysfunctions by removing abnormal immune cells that react against the body’s own cells. Earlier studies have suggested AHSCT can slow down neurological deterioration in SPMS, but controversies remain.

“In this study, we wanted to assess whether autologous hematopoietic stem cell transplants prolonged the time to confirmed disability progression compared to other disease-modifying therapies in SPMS,” the authors noted.

The current retrospective study was conducted on clinical data over a span of a decade from 79 SPMS patients who received autologous hematopoietic stem cells transplants (AHSCT) and 1,975 SPMS patients who received beta-interferons, azathioprine, methotrexate, cyclophosphamide, or other DMTs. Patients in the two groups were matched for age, sex, and level of disability.

The data was collected from the Italian Bone Marrow Transplantation Study Group and the Italian Multiple Sclerosis Register. The specific goal of the study was to compare the proportion of SPMS patients with confirmed disability progression (CDP) at six months who were treated with AHSCT versus other DMTs.

The degree of disability in patients was measured on the Expanded Disability Status Scale (EDSS), an established method to quantify disability with scores ranging from zero (no symptoms) to ten (death due to MS). At the outstart, all participants in both groups were given a median score of 6.5. Thereafter, participants were given a score of 6.0 when they occasionally needed to use a cane or brace to walk about 100 m with or without resting. When patients needed to use a cane or brace constantly on both sides to walk about 20 m without resting, they were given a score of 6.5.

The researchers found, after five years of treatment, 62% SPMS patients with AHSCT experienced no worsening of their disability compared to 46% of those who took other DMTs. Five years into the treatment, patients treated with AHSCT were also more likely to see sustained improvements over time, with 19% experiencing less disability than at the start of the study, compared to 4% of patients on medications. Over the span of a decade, the disability score for patients on AHSCT decreased by an average of 0.01 points annually while the average score for people on other DMTs increased by 0.16 points annually.

“Our study shows that hematopoietic stem cell transplants were associated with a slowing of disability progression and a higher likelihood of disability improvement compared to other therapies,” said Inglese. “While these results are encouraging, they are not applicable to patients with secondary progressive MS who do not have signs of inflammatory disease activity. More research is needed in larger groups of people to confirm our findings.”

Results of this retrospective and observational study suggest association but do not establish causal relation. Moreover, the study did not include all anti-inflammatory drugs prescribed to SPMS patients in the DMT group.

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