Background: Cladribine tablets 3.5 mg/kg cumulative over 2 years (CT3.5) had significant clinical/imaging effects in patients with clinically isolated syndrome (CIS; ORACLE-MS) or relapsing-remitting MS (RRMS; CLARITY and CLARITY Extension). This analysis compared the effect of cladribine tablets on the dynamics of immune cell reduction and reconstitution in ORACLE-MS, CLARITY, and CLARITY Extension during the first year of treatment (i.e. the first course of CT1.75) in patients randomized to CT3.5. Methods: Lymphocyte subtypes were analyzed using multiparameter flow cytometry. Changes in cell counts and relative proportions of lymphocytes were evaluated at weeks 5, 13, 24, and 48. Results: Across studies, consistent and comparable selective kinetics of immune cell populations occurred following the first treatment year with CT. A rapid reduction in CD16+/CD56+ cells (week 5 nadir), a more marked reduction in CD19+ B cells (week 13 nadir), and a less-pronounced effect on CD4+ (week 13 nadir) and CD8+ T cells (week 24 nadir) was shown. There was little effect on neutrophils or monocytes. Lymphocyte recovery began after treatment with CT3.5. Regarding relative proportions of naïve and memory T-cell subtypes in ORACLE-MS, the proportion of naïve-like naturally occurring T-regulatory cells (nTregs) decreased, and the proportion of memory-like nTregs increased, relative to total CD4+ T cells. Conclusions: CT3.5 has comparable effects on the immune systems of patients with CIS or RRMS. The pronounced reduction and recovery dynamics of CD19+ B cells and relative changes in the proportion of some immune cell subtypes may underlie the clinical effects of CT3.5.
Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.
The clinical course of 106 patients with brain metastases from breast cancer was retrospectively studied. Median time of survival after detection of intracranial metastases (SAR(ICM] was 14 weeks (95% confidence limits: 10-19 weeks), and 25% of the patients survived for more than 37 weeks, while only 17% survived for one year. The occurrence of clinical, pathoanatomical and therapeutical variables in these patients were analyzed in a subgroup of 57 patients, who survived for less than 16 weeks, and compared with a subgroup of 49 patients, who survived for more than 16 weeks after detection brain metastases. None of the variables studied were associated with either of the two prognostic groups. Patients with short SAR(ICM) had, however, a greater number of extra-cranial metastases at recurrence in the brain compared to patients with SAR(ICM) more than 16 weeks (p = 0.07). Patients with SAR(ICM) less than 16 weeks had a somewhat shorter recurrence-free interval (p = 0.22) and a significantly shorter time from primary diagnosis until detection of brain metastases (p = 0.04). Probably as a consequence of this, these patients had a shorter survival from primary diagnosis as well as from first recurrence. The findings may indicate that the differences in survival of patients with brain metastases are mainly due to differences in the rate of disease progression.
Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines.
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