Highlights of the 29th Congress of the European Committee for Treatment and Research in MS (ECTRIMS), Copenhagen, DK, October 2-5, 2013 – The Canadian MS HSCT Study is a phase II trial in which patients with aggressive MS receive ablative chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). The procedure appears to stabilize disease progression in a majority of patients, according to the results now presented (Freedman et al. ECTRIMS 2013; abstract P 543).
The regimen includes cyclophosphamide, anti-thymocyte globulin and busulphan as immunoablation prior to infusion of the immune cell-depleted graft. A total of 24 transplantations were performed in the period 2001-2009. Patients have been followed every three months for three years, then semi-annually for up to 10 years (median follow-up of 68 months). No patient received a disease-modifying therapy post-HSCT.
There was one death (4.1%) due to liver necrosis. In addition, one patient (4.1%) developed a serious toxicity (transient capillary leak syndrome). Late complications included premature ovarian failure (58.3%),varicella zoster reactivation (29.2%) and hypothyroidism (20.8%).
HSCT appeared efficacious in a majority of subjects. There have been no signs of inflammatory disease activity among any of the HSCT recipients. EDSS scores have stabilized or improved in 15 of 24 patients (62.5%). Eight patients (33.3%) experienced sustained EDSS progression. The rate of brain atrophy increased during chemotherapy, then normalized thereafter to the rate seen in healthy controls.
The group concluded that HSCT can re-establish a tolerant immune response and stop CNS inflammatory activity, although some patients will continue to demonstrate disease progression.
The Canadian MS/BMT Study Group recently reported that the reconstituted T cells demonstrate the same Th1/Th2 responses with similar autoreactivity to myelin as pre-transplantation, however, there is a diminished Th17 response post-transplantation (Darlington et al. Ann Neurol 2013;73:341-354).
Guest Reviewer: Dr. Paul S. Giacomini, Associate Director, MS Clinic, Montreal Neurological Hospital and Institute, Assistant Professor, Department of Neurology and Neurosurgery, McGill University, Montréal, Québec.