Medicine & Research

Promising research still leaves open questions

By Dr. Ben Thrower
Stem Cell Therapy Compares Well Against DMTs
Promising research still leaves open questions
By Dr. Ben Thrower
Autologous hematopoietic stem cell transplantation (HSCT) is an aggressive treatment that may also be one of the most effective options for relapsing-remitting MS. A recently published study looked at how the HSCT compares to standard disease-modifying therapies for MS.
            As the number of treatment options for MS expand, much thought is being given about which therapy is best and for which individual. We still have more treatment options for relapsing forms of MS than for progressive ones. Ocrelizumab (Ocrevus) is the only FDA-approved option for primary progressive MS. For RRMS, research is showing that more effective therapies such natalizumab, ocrelizumab, and alemtuzumab may offer better chances of disease control when started as first-line treatments. Given this shift in thinking towards more effective therapies, where does HSCT fit in?
            HSCT can be either allogeneic or autologous. The former means that the stem cells come from someone other than yourself, typically a relative or other closely matched donor. Autologous means the stem cells come from you. The advantage of an autologous transplantation is the lack of potential for rejection and the lack of need for long term antirejection medications.
            HSCT can be myeloablative or nonmyelo-ablative. This refers to how aggressive the accompanying chemotherapy is and whether all the existing bone marrow is shut down or not. Nonmyeloablative spares some of the cells in the bone marrow, and may have fewer health risks.
            MS results from an immune attack on myelin and axons in the central nervous system. HSCT, in effect, reboots the immune system resulting in a fresh immune system that should not attack myelin. There are several steps to HSCT:
1. Stem cell expansion. Medications are given to encourage the bone marrow to make more stem cells and send them into the blood stream.
2. Stem cell collection. Autologous stem cells are collected from the blood stream. Some HSCT procedures then make more of these stem cells by cloning them. The stem cells are then saved.
3. Conditioning. A regimen of chemotherapy is given to shut down the existing immune system. This can be myeloablative or nonmyeloablative.
4. Transplantation. The saved autologous stem cells are given back via an infusion.
5. Engrafting. The stem cells generate a new immune system. Cell recovery tends to take about a month.


            One of the leading HSCT research groups in the U.S. recently published results of a study in which patients with RRMS treated with HSCT were compared to patients treated with standard MS disease-modifying therapies. This was a nonmyeloablative autologous HSCT procedure. Most patients on standard DMTs were on glatiramer acetate or an interferon therapy. There were a handful of natalizumab patients and no ocrelizumab or alemtuzumab patients. The median length of time at follow-up was two years. What did we learn?
            Nonmyeloablative autologous HSCT appeared safe in this study. There were no deaths or serious side effects during the time that people were followed. Ideally, we would like to see many years of follow-up to make sure there are no long-term effects, such as cancers or cardiopulmonary complications due to the chemotherapy used in the conditioning regimen. Safety does appear to be improving as we learn more about HSCT. In years past, HSCT was associated with death rates as high as 3 percent.
            The procedure appeared to be effective. MS progression was much less common in the patients treated with HSCT versus standard DMTs. What we really need to know now is how HSCT compares in a large study to natalizumab, ocrelizumab, or alemtuzumab. These drugs are increasingly being used as first-line treatments in RRMS because of their effectiveness. Will HSCT be looked at as a similar first-line option in the future?
            HSCT researchers have learned from prior studies that the procedure works best in certain people. Who is an ideal HSCT candidate?
1. A person with active RRMS. Ideally, this person has active clinical relapses and/or active inflammation on MRI.
2. The person does not have a progressive form of MS. This is especially disappointing because we have limited treatment options for progressive MS patients.
3. The person is under the age of 50.
4. For now, most HSCT candidates have had ongoing MS activity despite trying a standard DMT or two. Again, as we learn more about HSCT, this may change.
            Currently, there are more people interested in the procedure than there are places performing it. This has led many in the U.S. who have MS to seek treatment in other places like Mexico or Russia. Be a smart consumer! Do your research and speak with others who have gone this route.
            HSCT may offer more and more people with MS an effective way of stopping MS in its tracks, but we need to know more. Hopefully, HSCT research will continue and give us another effective tool in the fight against MS.