Summary:seriously disabling, running a relapsing/remitting course which eventually becomes progressive (secondary proSeveral experimental autoimmune diseases (AID), gressive MS). In about 10-20% of cases it has a continuincluding allergic encephalomyelitis, ie the multiple ously progressive course from onset (primary progressive sclerosis (MS) model, respond to TBI and chemotherapy MS), which is slow or rapid, or even fulminant with shortfollowed by BMT. Remissions of AID may also occur ened survival. 2 There is strong evidence supporting an in patients with concomitant malignancies treated with immunopathogenic basis for the disease which could, thereallogeneic or autologous BMT. These observations have fore, be regarded as an autoimmune process directed at one emphasized the possibility of treating AID with highor other of the structural components of myelin. 3 Treatment dose therapy and haematopoietic stem cell transplaninvolves anti-inflammatory, immunosuppressive, and tation (HSCT). In a phase I/II pilot study, 15 patients immunomodulating agents, 4,5 some of which are active in with progressive MS were treated with BEAM followed managing relapses or preventing them, but none is curative. by autologous blood SCT and antithymocyte globulinMoreover, for patients with the progressive form of the dis-(ATG). Patients were severely disabled, with median ease, therapies are either unable to halt deterioration or have EDSS and SNRS scores of 6 (5-7.5) and 42 (33-62), modest effects on clinical improvement. ) and G/GMThe rationale for using haematopoietic stem cell trans-CSF (5 g/kg/day) were used for stem cell mobilization, plantation (HSCT) to treat MS is based on the principle of which caused no neurotoxicity. On days +1 and +2, ATG complete ablation of an aberrant immune system followed (2.5-5 mg/kg) was given for in vivo T cell-depletion.by reconstitution of a new immune system deriving from Allergy (93%) and infections (87%) were the principal either an allogeneic donor or a T cell-depleted autologous toxic complications. Mild, transient, neurotoxicity was transplant, as has been proposed for other autoimmune disobserved in six patients in the immediate post-transeases (AID). 12-16 Recapitulation of lymphocyte ontogeny plant period. The median follow-up time is 6 months may result in immune tolerance, especially in the allogeneic (6-18). Durable neurologic improvements have been setting in which a graft-versus-host reaction could contribdetected on both the EDSS (7/15) and SNRS (15/15) sysute to complete elimination of the patient's residual myelintems. One patient worsened at 3 months and two have reactive cells. 17 In the autologous setting it seems practirelapsed. Autologous HSCT appears feasible in MS; it cally impossible to eliminate all autoreactive cells, but the does not aggravate disability and seems to offer a clinipatient may still benefit from a strong conditioning regimen cal benefit. However, these observations need confirfollowed by a graft containing very few lymphocytes. mation and long-term ...
This study provides Class IV evidence that HSCT results in PFS rates of 25%. PFS rate was significantly better in patients with active MRI lesions; HSCT also resulted in a significant reduction in the number and volume of gadolinium-enhancing lesions on MRI.
Twenty patients diagnosed as having multiple sclerosis (MS) were examined by MRI and 9 neuropsychological scales: MMSE, BCRS, RMB, SDMT, BNT, VM, FAS, Benton and Hamilton. The number and distribution of the lesions, and cerebral and corpus callosum atrophy were evaluated by MRI. MR images were generated by a 0.5 Tesla instrument utilizing T1WI, PD and T2WI imaging techniques. The results reveal (1) that patients with MS are impaired in a broad range of cognitive functions but mainly memory is affected; (2) number of lesions in the corona radiata, insula and hippocampus is correlated with cognitive impairment, and (3) enlargement of the IIIrd ventricle is an indicator of memory impairment in MS patients.
Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases, we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy (BEAM regimen) followed by autologous blood stem cell rescue and antithymocyte globulin. Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- (or GM-) CSF. In 9 cases, additional CD34+ cell-selection of the graft was performed. Here we update previously published results of this novel treatment, mainly with regard to clinical efficacy, as the median follow-up time has reached 40 months (range, 21-51). Infections were the principal toxicity early after the procedure, with death of a patient from aspergillosis 65 days post stem cell infusion. No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34+ cell-depleted graft. Mild and transient neurotoxicity was observed in 10 patients (42%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment, i.e., they were improved or stabilized, while five patients progressed, of which 4 had primary progressive disease. Of those improved or stabilised (18), 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression, although their disability scores have not gotten worse than they were before transplantation. The probability of progression-free survival (compared to entry status) at 3 years is 92% for patients with secondary progressive disease and 39% for the primary progressive type. CD34+ cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those achieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with this disease.
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