The number of CD34+ cells harvested in a single leukapheresis can be predicted by measurement of the preceding day peripheral-blood circulating CD34+ concentration, and on the basis of these data a table of probable CD34+ cell yield has been constructed. This correlation may facilitate the efficient organization of leukapheresis procedures.

Thirty‐six patients with multiple myeloma (23 PR1, nine PR2, four stable disease) were entered into a pilot study evaluating the use of CD34+‐selected peripheral blood progenitor cell transplantation (PBPCT) following high‐dose melphalan alone or high‐dose melphalan and total body irradiation. Peripheral blood progenitor cells (PBPCs) were mobilized with cyclophosphamide and granulocyte colony stimulating factor (G‐CSF). CD34+ selection using the Cellpro Ceprate‐SC system was performed in 22 cases with an adequate yield in 20. 10 patients failed to mobilize sufficient cells to permit selection and in four cases selection was not performed for other reasons. 16 patients therefore received unselected PBPC. Tumour cell contamination was evaluated by IgH gene fingerprinting (fpPCR). Harvested PBPC were fpPCR positive in 13/20 CD34+‐selected cases and remained positive after selection in seven. Harvested PBPC were studied in 9/16 patients receiving unselected cells; fpPCR was positive in five and negative in four. There was no difference in event‐free survival (EFS) between the CD34+‐selected group and the unselected group (median 21 and 26 months, respectively, P=ns). The CD34+‐selection process therefore reduced contamination but did not eliminate it completely, and in this small non‐randomized study there was no apparent clinical benefit of CD34+selection.

Summary High-dose etoposide (2.0-2.4 g m-2) with granulocyte colony-stimulating factor (G-CSF) is an effective strategy to mobilize perpheral blood progenitor cells (PBPCs), although in some patients this is associated with significant toxicity. Sixty-three patients with malignancy were enrolled into this non-randomized sequential study. The majority (55/63, 870,o) had received at least two prior regimens of chemotherapy. and seven patients had previously failed to mobilize following high-dose cyclophosphamide with G-CSF. Consecutive patient groups received etoposide at three dose levels [2.0 g m-2 (n = 22). 1.8 g m-2 (n = 20) and 1.6 g m-2 (n = 21)] followed by daily G-CSF. Subsequent leukaphereses were assayed for CD34-cell content, with a target total collection of 2.0 x 106 CD34-cells kg-'. Toxicity was assessed by the development of significant mucositis. the requirement for parenteral antibiotics or blood component support and rehospitalization incidence. Ten patients (169o) had less than the minimum target yield collected. Median collections in the three groups were 4.7 (2 g m-2). 5.7 (1.8 g m-2) and 6.5 (1.6 g m-2) x 106 CD34-cells kg-'. Five of the seven patients who had previously failed cyclophosphamide mobilization achieved more than the target yield. Rehospitalization incidence was significantly lower in patients receiving 1.6 g m-2 etoposide than in those receiving 2.0 g m-2 (P = 0.03). These data suggest that high-dose etoposide with G-CSF is an efficient mobilization regimen in the majority of heavily pretreated patients, including those who have previously failed on high-dose cyclophosphamide with G-CSF. An etoposide dose of 1.6 g m-2 appears to be as effective as higher doses but less toxic.

Background: Type 1 Diabetes Mellitus (T1DM) is partly driven by autoimmune destruction of the pancreatic beta cell, facilitated by the release of inflammatory cytokines, including IFN-γ, TNF-α and IL-1β by cells of the innate immune system. Mesenchymal Stem Cells (MSCs) have been used to counteract autoimmunity in a range of therapeutic settings due to their secretion of trophic and immunomodulatory factors that ameliorate disease independently of the cells themselves. Objective: The aim of this study was to assess the effect of the secretome of human bone-marrow derived MSCs on cytokine-driven beta cell apoptosis. Methods: All experiments were conducted in two insulin-secreting islet cell lines (BRIN-BD11 and βTC1.6) with selected experiments confirmed in primary islets. MSC secretome was generated by conditioning serum-free media (MSC-CM) for 24 hours on sub-confluent MSC populations. The media was then removed and filtered in readiness for use. Results: Exposure to IFN-γ, TNF-α and IL-1β induced apoptosis in cell lines and primary islets. The addition of MSC-CM to cell lines and primary islets partially reversed cytokine-driven apoptosis. MSC-CM also restored glucose-stimulated insulin secretion in cytokine-treated cell lines, which was linked to improved cell viability following from cytokine challenge. Characterization of MSC-CM revealed significant concentrations of IL-4, IL-10, PIGF and VEGF. Of these, IL-10 alone prevented cytokine-driven apoptosis. Furthermore, the inhibition of IL-10 through the addition of a blocking antibody reversed the anti-apoptotic effects of MSC-CM. Conclusion: Overall, the protective effects of MSC-CM on islet beta cell survival appear to be largely IL-10-dependent.

Introduction Cardiovascular disease (CVD) is the leading cause of mortality in people with Type 2 diabetes mellitus (T2DM). Statins reduce low‐density lipoproteins and positively affect CVD outcomes. Statin type and dose have differential effects on glycaemia and risk of incident T2DM; however, the impact of gender, and of individual drugs within the statin class, remains unclear. Aim To compare effects of simvastatin and atorvastatin on lipid and glycaemic control in men and women with and without T2DM, and their association with incident T2DM. Methods The effect of simvastatin and atorvastatin on lipid and glycaemic control was assessed in the T2DM DiaStrat cohort. Prescribed medications, gender, age, BMI, diabetes duration, blood lipid profile and HbA1c were extracted from Electronic Care Record, and compared in men and women prescribed simvastatin and atorvastatin. Analyses were replicated in the UKBiobank in those with and without T2DM. The association of simvastatin and atorvastatin with incident T2DM was also investigated in the UKBiobank. Cohorts where matched for age, BMI and diabetes duration in men and women, in the UKBioBank analysis, where possible. Results Simvastatin was associated with better LDL (1.6 ± 0.6 vs 2.1 ± 0.9 mmol/L, p < .01) and total cholesterol (3.6 ± 0.7 vs 4.2 ± 1.0 mmol/L, p < .05), and glycaemic control (62 ± 17 vs 67 ± 19 mmol/mol, p < .059) than atorvastatin specifically in women in the DiaStrat cohort. In the UKBiobank, both men and women prescribed simvastatin had better LDL (Women: 2.6 ± 0.6 vs 2.6 ± 0.7 mmol/L, p < .05; Men: 2.4 ± 0.6 vs 2.4 ± 0.6, p < .01) and glycaemic control (Women:54 ± 14 vs 56 ± 15mmol/mol, p < .05; Men, 54 ± 14 vs 55 ± 15 mmol/mol, p < .01) than those prescribed atorvastatin. Simvastatin was also associated with reduced risk of incident T2DM in both men and women (p < .0001) in the UKBiobank. Conclusions Simvastatin is associated with superior lipid and glycaemic control to atorvastatin in those with and without T2DM, and with fewer incident T2DM cases. Given the importance of lipid and glycaemic control in preventing secondary complications of T2DM, these findings may help inform prescribing practices.