Autologous hemopoietic stem cell transplantation for multiple sclerosis: is it worthwile?

High-dose immunosuppressive chemotherapy or total body irradiation followed by autologous transplantation of hemopoietic stem cells (ASCT) was introduced in the treatment of active, progressing, and therapy-resistant multiple sclerosis (MS) in 1995. Since then, more than 300 patients have undergone this sort of treatment worldwide and the European Group for Blood and Marrow Transplantation (EBMT) published on two occasions, in 2002 and in 2006, the results of collective analyses performed in 85 and in 183 cases, respectively. In most communications the results were reported favorable with some cases showing spectacular recoveries and also probabilities of long-lasting disease stability, between 60 and 80% at three years after transplant. Of great interest was the fact that magnetic resonance imaging studies invariably showed that the inflammation in the central nervous system resolved and gadolinium-enhancing lesions were completely abolished or markedly reduced. These results appear superior to those yielded by standard therapies but this superiority needs to be demonstrated by comparative studies, such as the EBMT-launched ASTIMS trial. Moreover, ASCT is a rather toxic procedure associated with a mortality risk of 2-3%. Therefore, it is not a treatment for the general population of MS patients but only for selected cases that do not respond to standard therapies and worsen rapidly, i.e. in situations where benefits are expected to counterbalance morbidity and mortality risks. Nevertheless, certain issues seem to have cleared up: ASCT should be used early, during the inflammatory phase of the disease; very high-intensity pre-transplant conditioning regimens increase toxicity but do not seem to increase efficacy compared to intermediate-intensity regimens; the results are dramatic and life-saving in resistant, so-called "malignant" cases; ASCT does not only cause debulking of autoreactive clones but it also brings about qualitative immunological changes that might eventually establish immunologic self-tolerance; the progression of brain atrophy appears to slow down with time; with the implementation of proper patient-selection criteria, the risks of morbidity and mortality can be minimized.