Background: HSCT (Hematopoietic Stem Cell Transplantation)
- A nationwide team of researchers published results from a small, five-year study of transplantation of individuals’ own hematopoietic (blood cell-producing) stem cells combined with high-dose immunotherapy in 24 people with aggressive relapsing-remitting MS that was not controlled by available disease-modifying therapies.
- This procedure aims at “rebooting” the immune system to prevent MS immune attacks against the brain and spinal cord.
- At five years, 69.2% of participants experienced remission, with no new disease activity.
- All participants experienced severe and/or life threatening adverse events. Most of these occurred within the first 30 days after transplant and were related to low white blood cell counts and infections. Three participants experienced disease progression and died during the study, the deaths were not thought to be related to the procedure.
- This study, known as High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS), was a phase II clinical trial funded by the National Institutes of Health. The team (Richard A. Nash, MD, Colorado Blood Cancer Institute, Denver, and colleagues) has published results in Neurology (2017;88:1–11).
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, and then 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.
This study, known as High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS), was a phase II clinical trial. Results at three years have been published
, and the five-year results were previously reported
at the Annual Meeting of the Consortium of MS Centers in 2016. This study was funded by the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, and conducted by the Immune Tolerance Network.
Investigators enrolled 25 people with relapsing-remitting MS who had experienced 2 or more relapses and disease progression during the previous 18 months while taking disease-modifying therapies. Participants underwent the HSCT procedure, and were followed for five years. The primary endpoint of this study was whether participants experienced “event-free survival,” meaning that they did not have an increase in disease activity or die. Disease activity was defined as confirmed loss of neurologic function (progression of disability), clinical relapse, or new lesions observed on MRI scans.
After five years, 69.2% of the participants were still in remission and free of disease activity (compared with 95.8% after one year). Treatment failed in seven individuals. Among survivors, scores on clinical scales measuring disease activity and quality of life, including the EDSS, improved significantly at five years after HSCT. Immune system analysis at three years had shown prolonged depletion of the immune cells that drive the immune attack, indicating that the immune system was indeed “rebooted.”
One individual experienced a pulmonary embolism induced by heparin (administered as part of stem cell collection), and withdrew from the study. Three deaths occurred (from cardiorespiratory arrest, complications due to MS progression, and asthma), which were not thought to be related to the procedure. Severe adverse events occurred in 23 participants, and life-threatening adverse events occurred in all participants. Most of these occurred within the first 30 days after transplant and were related to low white blood cell counts and infections. “Although there were no treatment-related deaths in the HALT-MS study, there is a significant risk associated with transplant and patients require counseling regarding this,” write the authors.
The team (Richard A. Nash, MD, Colorado Blood Cancer Institute, Denver, and colleagues) has published results in Neurology
“This important study contributes to the accumulating knowledge of the possible benefits and risks of bone marrow stem cell transplantation in relapsing MS,” says Bruce Bebo, PhD, the National MS Society’s Executive Vice President, Research. “Larger, well-controlled trials are needed to better understand who might benefit from this procedure and how it compares to the benefits of powerful immune-modulating therapies now available.” A phase III trial of HSCT is now in planning stages.
Read the open-access paper in Neurology
Read more about HSCT, including the procedures involved and FAQs
Read more about stem cells in MS