A study of 21 adults with relapsing-remitting multiple sclerosis (MS) has found that a technique called autologous non-myeloablative haemopoietic stem cell transplantation1 can stabilise, and may reverse, neurological disability. The findings of this phase I/II study are reported in an Article that is due to be published Online First and in the March issue of The Lancet Neurology.
MS is an autoimmune disease that at first is characterised by intermittent symptoms that are commonly partly reversible (called the relapsing-remitting phase). Over 10 years after onset, most patients develop secondary-progressive MS, characterised by gradual but irreversible neurological impairment. The available treatments for MS are effective mainly in the relapsing-remitting phase; however, some patients do not respond to these treatments, meaning that more options are needed.
One option that has emerged over the past few years is to suppress the immune system and replenish it with new cells that develop from haemopoietic stem cells. This treatment uses a conditioning regimen2 to remove lymphocytes3 that are self-reactive against the immune system and damaging to the central nervous system in patients with MS, and is followed by reconstitution of the immune system with haemopoietic stem cells taken from the patient's bone marrow. The resulting new lymphocytes are self-tolerant (ie, they do not react against the immune system) and the patient's immune system is "reset".
Richard K Burt (Northwestern University Feinberg School of Medicine, Chicago, IL, USA) and colleagues assessed the safety and clinical outcome of this transplantation technique in 21 patients (11 women and 10 men) with relapsing-remitting MS who had not responded to at least 6 months' treatment with interferon beta.4 By contrast with previous studies of autologous haemopoietic stem cell transplantation in MS, the participants in this study were young (average age 33 years; range 20), were in the relapsing-remitting phase, and did not have severe disability. The participants had had MS for an average of 5 years.
After an average follow-up of 3 years, 17 patients (81%) improved by at least 1 point on a disability scale.5 No patient had a final score on the scale that was lower than their score before transplantation (ie, progression-free survival was 100% in the study).
In addition to the improvements in neurological function noted during the study, the procedure was well tolerated. One patient had diarrhoea due to a bacterial infection, two had viral infections, and two patients developed thrombocytopenic purpura related to the conditioning treatment they received.2 All of these events resolved with treatment. Five patients relapsed, but achieved remission after receiving other immunosuppressive therapy.
Although further studies are needed, "autologous non-myeloablative haemopoietic stem cell transplantation for patients with relapsing-remitting MS with active inflammatory disease and frequent exacerbations is a feasible procedure that not only seems to prevent neurological progression, but also appears to reverse neurological disability", the researchers conclude.
In an accompanying Reflection and Reaction Comment, Gianluigi Mancardi (San Martino Hospital, University of Genova, Italy) discusses the role of autologous non-myeloablative haemopoietic stem cell transplantation for patients with MS: "the results imply that this is a valuable alternative to the transplant conditioning therapies used so far", he says.
Dr Richard K Burt, Northwestern University Feinberg School of Medicine, Chicago, IL, USA T) +1 312 908 0059 E) rburt@northwestern.edu
Professor Gianluigi Mancardi, San Martino Hospital, University of Genova, Italy E) glmancardi@neurologia.unige.it (contact by e-mail only)
For full Article and Reflection and Reaction, see: http://press.thelancet.com/TLNMSfinal.pdf
Notes to Editors
1 Haemopoietic stem cells give rise to blood cells. Autologous indicates that the cells are obtained from the patient who subsequently receives the transplant, and non-myeloablative refers to the method (the conditioning regimen) used to remove potentially self-reactive cells.
2 In this study, the researchers used a low-intensity (non-myeloablative) conditioning regimen: the first 17 patients received cyclophosphamide and alemtuzumab; the other four patients received cyclophosphamide and rabbit antithymocyte globulin, after the US Food and Drug Administration reported that alemtuzumab was associated with a blood-clotting disorder called thrombocytopenic purpura. More intensive conditioning regimens (such as irradiation of the whole body) have been associated with high mortality.
3 Lymphocytes are white blood cells that are important in immune responses.
4 Interferon beta is an approved treatment for relapsing-remitting MS.
5 The researchers used the Kurtzke expanded disability status scale (EDSS)—a validated and widely used score to measure the outcome of patients with MS.
Journal
The Lancet Neurology