SUMMARY
- An international team of researchers published results from a small study of immunosuppressant therapy followed by hematopoietic (blood cell-producing) stem cells in people with aggressive relapsing-remitting MS that was not controlled by available disease-modifying therapies.
- This procedure aims to “reboot” the immune system to slow down or prevent MS immune attacks against the brain and spinal cord.
- The study achieved its primary endpoint, with significantly fewer people experiencing MS progression in the group that underwent HSCT, compared with the group who were switched to a different MS disease-modifying therapy. There were no deaths or life-threatening adverse events in either group.
- This was the first randomized controlled clinical trial of HSCT for relapsing MS. The team (Richard K. Burt, MD, Northwestern University, Chicago, IL, and colleagues) published the results in JAMA Neurology (2019;321(2):165-174). The investigators consider this study to be preliminary and recommend that further research is needed to confirm these findings and to determine longer-term outcomes and safety.
- In an editorial published in the same issue of the journal, Dr. Harold Atkins (Ottawa Hospital Blood and Marrow Transplant Program, University of Ottawa) notes that HSCT for autoimmune diseases is a procedure that requires highly specialized medical expertise in multiple sclerosis management and cell-based therapies to minimize risks.
DETAILS
Background: HSCT (Hematopoietic Stem Cell Transplantation) attempts to “reboot” the immune system, which is involved in damaging the brain and spinal cord in MS. In HSCT for MS, hematopoietic (blood cell-producing) stem cells, which are derived from a person’s own “autologous” bone marrow, are collected and stored, and the rest of the individual’s immune cells are depleted by chemotherapy. Then the stored hematopoietic stem cells are reintroduced to the body. The new stem cells migrate to the bone marrow and over time reconstitute the immune system.
The Study: For this randomized, controlled clinical trial of HSCT in relapsing MS, investigators at Northwestern University (Chicago, Illinois), Sheffield Teaching Hospitals (Sheffield, England), University of Uppsala (Uppsala, Sweden), and University of São Paulo (Ribeirão Preto, Brazil) enrolled 110 people, 18 to 55 years of age, who had aggressive relapsing-remitting MS. To be enrolled participants had to have experienced at least 2 relapses (or 1 relapse and MRI evidence of disease activity at a separate time) despite treatment with disease-modifying therapies (DMT) in the previous year. Individuals with less aggressive MS and those with progressive forms of MS were excluded from the study.
Fifty-five were randomly assigned to undergo HSCT, and 55 were randomly assigned to receive a different type or stronger DMT than the therapy they had taken the year before. A provision of the study allowed participants in the DMT group to receive HSCT if they experienced progression of disability after one year in the study.
The primary endpoint of the trial was sustained disease progression after at least 1 year, defined as a worsening of EDSS score of 1 point. The EDSS is a standard scale that measures physical disability. The professionals who measured participants’ EDSS were not aware of (blinded) their treatment group. The team also tracked safety, relapses and other outcomes.
Key Results: The study met its primary endpoint, with significantly fewer people in the HSCT group experiencing disease progression after 1 year compared to those in the DMT group: progression occurred in 3 out of 52 people in the HSCT group and in 34 out of 51 people in the DMT group. Progression increased over time, but significantly fewer progressed over time in the HSCT group compared to the DMT group.
In the first year, 1 person out of 51 experienced an MS relapse in the HSCT group, compared to 36 out of 52 in the DMT group. Significantly fewer experienced relapse over time in the HSCT group compared to the DMT group.
The HSCT group also showed significantly less disease activity on MRI scans at 1 year and showed improvement in scores on a scale measuring quality of life (Short Form 36). Those who underwent HSCT after being in the DMT group for one year generally tended to do well.
Safety: There were no deaths in either group. There were no disabling or potentially life-threatening events immediately after HSCT. There were three cases of in-patient infections and 31 post-transplantation infections, mostly upper respiratory, urinary tract infections, and shingles. Idiopathic thrombocytopenic purpura, a serious bleeding disorder, occurred in two people in the HSCT group, and four in the HSCT group developed autoimmune thyroid disease.
The team (Richard K. Burt, MD, Northwestern University, Chicago, IL, and colleagues) has published results in
JAMA Neurology (
2019;321(2):165-174). In the paper, the investigators point out limitations of the study, including the small number of participants available to evaluate longer-term outcomes, and the fact that some of the more recently available, powerful disease-modifying therapies such as alemtuzumab and ocrelizumab were not among the therapies offered to those in the DMT group. The investigators consider this study preliminary, and recommend that further research is needed to confirm these findings and to determine longer-term outcomes and safety.
Comment: “This important trial adds to accumulating evidence of the possible benefits of bone marrow stem cell transplantation in people with aggressive relapsing MS who have not benefited from conventional disease-modifying therapy,” said Bruce Bebo, PhD, the National MS Society’s Executive Vice President, Research. “It is not yet clear who are the best candidates for this procedure, or which is the optimal regimen, and how the benefits and risks compare to those of powerful immune-modulating therapies. At least one larger, phase 3 controlled trial is now underway to help answer these important questions.”
In an editorial published in the same issue of the journal, Dr. Harold Atkins (Ottawa Hospital Blood and Marrow Transplant Program, University of Ottawa) notes that HSCT for autoimmune diseases is a procedure that requires highly specialized medical expertise in multiple sclerosis management and cell-based therapies to minimize risks.
Learn More
Read the scientific abstract in JAMA Neurology
Read more about HSCT, including the procedures involved and FAQs
Learn more about stem cells in MS