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Combined Analysis of Previously Published HSCT/Bone Marrow Transplantation Studies

May 4, 2017

  • Researchers in Italy combined and analyzed results from 15 previously published studies of HSCT (Hematopoietic Stem Cell Transplantation) involving 764 people with various forms of MS, and published results on April 28, 2017 in Neurology.
  • Overall, the procedure showed a significant benefit against disease activity and progression. Two years after transplantation, about 83% of all participants had not progressed; overall, studies involving more people with relapsing-remitting MS had lower progression rates.
  • The pooled results showed an overall transplant-related mortality rate of 2.1%. There were fewer deaths in later studies as researchers gained more experience with the procedure. Transplant-related mortality was lower in studies conducted after 2005 (1 death out of 349 patients, or 0.3%), compared to 3.6% in older studies.
  • Additional information and comments are below. 
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 then collected and stored, and the rest of the individual’s immune cells are depleted by chemotherapy. Then the stored hematopoietic stem cells are re-introduced to the body. The new stem cells migrate to the bone marrow and over time reconstitute the immune system. The goal is to reset the immune system and stop the inflammation that contributes to active relapsing MS.
The Study: Dr. Maria Pia Sormani, Gian Luigi Mancardi (University of Genoa, Italy) and collaborators combined and analyzed the results from 15 HSCT studies previously published from 1995 to 2016. This goal of this type of “meta-analysis” is meant to provide a big-picture view of multiple smaller studies. All but one of the studies were conducted “open label,” which means that there was no blinding or placebo controls and the doctors and participants were aware of the treatment they were receiving.  
  • The number of participants involved in the individual studies ranged from 7 to 178, with a total of 764 people with MS.
  • Participants varied in terms of age (9 to 64), levels of disability (1.5 to 9.0 EDSS), disease duration (0.2 to 28 years) and types of MS (relapsing, progressive or not indicated).  
  • Strength of the immune-suppressing regimens used before transplantation varied, and included low-intensity, intermediate intensity, and high intensity. 
Results: Key findings of this meta-analysis include:
  • Safety: The pooled results showed an overall transplant-related mortality rate of 2.1%. Transplant-related mortality was lower in studies conducted after 2005 (1 death out of 349 patients, or 0.3%), compared to 3.6% in older studies. Studies that included a higher proportion of people with relapsing-remitting MS had a lower mortality rate (1%), and studies that included people with higher levels of disability had a higher mortality rate. 
  • Progression: Overall, at two years after transplantation, 17.1% of all participants had progressed, and 82.9% had not. In studies that included a higher proportion of people with relapsing-remitting MS, 7.8% had progressed, compared to 24.8% in studies that included people with a lower proportion of people with relapsing-remitting MS.
  • Disease Activity: An evolving measure of treatment benefit is called “No Evidence of Disease Activity” or NEDA. NEDA is achieved if there were no relapses, no progression, and no new signs of disease activity on MRI scans. In five studies that reported NEDA at 2 years (involving 274 patients), 83.4% had NEDA. In four studies that reported NEDA at 5 years (involving 233 patients), 67% had NEDA.   
Most of the studies did not employ control groups to compare HSCT to a standard therapy or placebo, and, as noted by the authors of the study, “It is difficult to compare outcomes of aHSCT with those reported in clinical trials of drugs for MS, since the population eligible to receive aHSCT generally has much more aggressive or advanced forms/stages of MS than the ones enrolled in clinical trials.” 
The paper was published early online on April 28, 2017 in Neurology.
Comment: This paper compiles results from a number of small and larger studies of HSCT in MS, and shows results related to the procedure’s safety and effectiveness. “It’s becoming clear that improvements in the procedure and patient selection have made this safer when it is performed in centers with extensive experience,” says Bruce Bebo, PhD, the National MS Society’s Executive Vice President, Research. “We still need well-controlled trials to better understand who will benefit from this procedure and how it compares to the risks and benefits of the FDA-approved disease-modifying treatments. At least one phase 3 trial of HSCT is underway and another is in planning stages, so we should have a much better idea of how HSCT can best be used to treat MS in the near future.”
Next Steps:
  • The Society has formed a Work Group on HSCT in MS Management to discuss what is known and what we still need to know about HSCT, and provide guidance on information, resources and advice the Society should provide for people with MS, healthcare professionals and payers.
  • In addition, the Society is engaged with the team planning a phase 3 trial of HSCT and is encouraging quick action to design and launch the trial.
  • With research rapidly advancing, in November 2015 the Society co-sponsored the International Conference on Cell-Based Therapy for Multiple Sclerosis in Lisbon, Portugal. HSCT was among the topics covered, with participation from HSCT experts including Dr. Mark Freedman (University of Ottawa), Dr. Richard Burt (Northwestern University) and Dr. Gian Luigi Mancardi (University of Genoa) and 70 other leading researchers and clinicians. A review of the findings and consensus on next steps will be published by the conference organizers, with recommendations to help speed the development of new cell-based treatment solutions, including HSCT.
Read more about HSCT, including the procedures involved and FAQ (.pdf)
Read about another recent study of HSCT
Read more about stem cells in MS

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.