Hematological effects of intermittent 2-hour infusions of cladribine in multiple sclerosis patients: a comparison of 2 dosage patterns.

Cladribine is a lymphocytotoxic purine nucleoside with potential for treatment of autoimmune diseases. However, optimal administration regimens remain to be established. Twenty multiple sclerosis patients enrolled into this study were given 30 intermittent 2-hour cladribine infusions (0.07 mg/kg per infusion) each. Ten patients received cycles of 5 consecutive daily infusions at 5-week intervals (clustered dosage) on an inpatient basis; the other 10 patients received 1 infusion weekly (nonclustered dosage) on an outpatient basis. Red blood cell (RBC), platelet, and total white blood cell (WBC) counts were assessed at 5-week intervals during the treatment and at 13-week intervals during a 26-week follow-up period. Major WBC and lymphocyte subsets were assessed cytometrically at 15-week intervals during the treatment and at 13-week intervals thereafter. The clustered dosage produced a lasting decline in granulocyte count, a delayed decrease in monocyte count, and a transient decrease in RBC count. The nonclustered dosage caused a larger and persistent decline in RBC count, a smaller (P = .051. compared over the study period) decrease in monocyte count, and no change in granulocyte count. Both regimens transiently reduced natural killer and B-cell subsets (by 40%-60% and >80%, respectively) and caused lasting declines in CD4+ T-cell subsets (by >50%). No significant change was found in CD8+ T-cell subsets. These results show similar potency of these regimens with respect to major lymphocyte subsets, while suggesting that the nonclustered dosage is less toxic to myeloid precursors and more toxic to erythroid lineage precursors.

CDP-choline, but not cytidine, protects hippocampal CA1 neurones in the gerbil following transient forebrain ischaemia.

The effects of CDP-choline (citicoline), cytidine monophosphate or cytidine on the number of CA1 hippocampal neurones surviving five-minute forebrain ischaemia have been evaluated in gerbils. The substances tested were given in daily doses equivalent on a molar basis to 500 mg/kg CDP-choline, starting immediately after ischaemia. On day five the brains were perfused, postfixed, cut into 10 microm slices and stained with cresyl violet, and the number of neurones in the CA1 sectors was counted manually under a light microscope at magnification x 400. The results indicate a significant degree of protection provided by citicoline, but no protection by cytidine monophosphate or cytidine. The choline moiety of CDP-choline appears to be essential for the neuroprotective properties of the drug.

Survival and maturation of heterotopic fetal brain stem xenografts after treatment with 2-chlorodeoxyadenosine and cyclosporine A.

Brain stem halves from fetal rabbits were transplanted to the caudate nucleus area of adult rats. The animals were treated postoperatively with cyclosporine A (CsA) and 2-chlorodeoxyadenosine (CdA) for three days, and with CdA alone for the next 13 days. The treatment started at the day of implantation, and in some animals it was repeated starting at day 36 after grafting (at the time when signs of a light inflammatory reaction appeared in some grafts). Grafts survived and matured histologically, and no signs of acute rejection were observed up to the 90th day. In some grafts we recorded phasic neuronal activities similar to the respiratory-related neural activities characteristic for the adult brain stem. Immunosuppressive with CdA and CsA deserves further evaluation in fetal brain grafting.