No abstract

Over the last decade, hematopoietic stem cells transplantation (HSCT) has been increasingly used in the treatment of severe progressive autoimmune diseases. We report a retrospective survey of 183 multiple sclerosis (MS) patients, recorded in the database of the European Blood and Marrow Transplantation Group (EBMT). Transplant data were available from 178 patients who received an autologous graft. Overall, transplant related mortality (TRM) was 5.3% and was restricted to the period 1995-2000, with no further TRM reported since then. Busulphan-based regimens were significantly associated with TRM. Clinical status at the time of transplant and transplant techniques showed some correlations with toxicity. No toxic deaths were reported among the 53 patients treated with the BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan)/antithymocyte globulin (ATG) regimen without graft manipulation, irrespective of their clinical condition at the time of the transplant. Improvement or stabilization of neurological conditions occurred in 63% of patients at a median follow-up of 41.7 months, and was not associated with the intensity of the conditioning regimen. In this large series, HSCT was shown as a promising procedure to slow down progression in a subset of patients affected by severe, progressive MS; the safety and feasibility of the procedure can be significantly improved by appropriate patient selection and choice of transplant regimen.

Aim ofthe study: To validate the MMSE in Greece. Materials and Methods: 151 subjects took part in the study-64 non-demented subjects (42 males and 22 females) and 87 demented patients (44 males and 43 females), sufferingfrom mild to severe dementia ofvarious types (Alzheimer's disease, vascular dementia, and dementia secondary to other causes). The dementedpatients' age was 68.05 ± 11.72 years (mean ± standard deviation), their education 5.71 ± 2.95 years. The normal subjects' age was 68.57 ± 10.32 years and education was 6.18 ± 3.20 years. The diagnosis was made according to the DSM-IV and the NINCDS-ADRDA diagnostic criteria. Results: MMSE appeared to be valid during test and retest with a Spearman 's coefficient p = 0.98 (p < 0.001). At the score level of23/24, sensitivity is 90.80, specificity 90.62 andpositive predictive value (PPV) of92.94. Conclusion: The present study confirms the MMSE score 23/24 as a valid cutoff levelfor the diagnosis of dementia in Greece.

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 ...