Summary:The cryoprotectant dimethyl sulfoxide (DMSO) is known to have toxic side effects, yet guidelines for its use in stem cell transplantation do not exist. To assess current practice in the use of DMSO and the incidence of DMSO-related complications, a single page questionnaire was mailed to 444 EBMT centres involved in autologous transplantation. The responses from 97 centres showed a wide variation in practice between transplant units regarding the concentration of DMSO used, daily DMSO dose restriction and the use of cell washing. The overall incidence of DMSO toxicity was approximately one in 70 transplants and most cases were cardiovascular and respiratory in nature. There was a trend to reduced complication rates in centres using lower concentrations of DMSO or washing cells prior to return. A large-scale prospective study of the strategies for reduction in exposure to DMSO and reduction in toxic effects is required before guidelines in the use of DMSO in stem cell cryopreservation can be promulgated. Bone Marrow Transplantation (2005) 36, 601-603.

No abstract

The 26S proteasome is a multicatalytic protease responsible for regulated intracellular protein degradation. Its function is mediated by three main catalytic activities: (a) chymotrypsinlike (CT-L), (b) trypsin-like, and (c) peptidylglutamyl peptide hydrolysing (PGPH). Proteasome inhibition is an emerging therapy for many cancers and is a novel treatment for multiple myeloma. Here, we profile the contributions of the three catalytic activities in multiple myeloma cell lines and compare the specificity and cytotoxicity of the novel proteasome inhibitor BzLLLCOCHO and inhibitors PS-341 (Velcade, bortezomib) and MG-132. Using fluorogenic substrates and an active site-directed probe specific for proteasome catalytic subunits, we show differential subunit specificity for each of the inhibitors. Addition of BzLLLCOCHO strongly inhibited all three catalytic activities, treatment with PS-341 completely inhibited CT-L and PGPH activities, and treatment with MG-132 resulted in weak inhibition of the CT-L and PGPH activities. Multiple myeloma cells were more sensitive to induction of apoptosis by PS-341 and MG-132 than BzLLLCO-CHO. This study emphasizes the need for further investigation of the effects of these compounds on gene and protein expression in the cell to allow for the development of more specific and targeted inhibitors. (Cancer Res 2006; 66(12): 6379-86)

Cancer Research UK, Janssen-Cilag, and Chugai Pharma UK.

Summary.A quantitative analysis of peripheral blood stem cell (PBSC) yield, measuring absolute numbers of CD34 þ cells × 10 6

No abstract

Lymphocytes have long been established to play an important role in the regulation of hematopoiesis and produce many cytokines that act on hematopoietic progenitor cells. Previous studies by our group have shown that normal, unstimulated lymphocytes produce a protein that inhibits normal bone marrow GM colony formation. Adiponectin is an adipokine that has been demonstrated to act as a negative regulator of hematopoiesis and immune function. This study aimed to determine if the inhibitory molecule that we described previously was adiponectin. Here, we show transcription, translation, and secretion of adiponectin from lymphocytes and demonstrate that its receptors, AdipoR1 and AdipoR2, are expressed by bone marrow MNCs. We show that although the adiponectin expression is low in lymphocytes, it is sufficient to induce a significant inhibitory effect on GM precursors (CFU-GM) and activate the AMPK pathway in these cells. The regulation of adiponectin production by lymphocytes and its detailed function in suppressing GM colony formation need to be elucidated now. Our findings suggest a functional role for adiponectin as a negative regulator of granulopoiesis.

Aims-To assess whether r-HuEPO (recombinant human erythropoietin) has any effect on thrombopoiesis in patients with chronic renal failure.Methods-This was a retrospective study of 78 patients with chronic renal failure undergoing either haemodialysis (n = 57) or intraperitoneal dialysis (n = 21). All patients had a full blood count (in EDTA) me before stling r-HuEPO and at monthly intervals thereafter up to six months. Variables studied were haematocrit, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW). Other groups of control patients were also studiedpatients with chronic renal failure receiving dialysis but not r-HuEPO (n = 40) and a group of patients with normal renal function who were receiving aspirin (n = 30). Results-There was a significant increase in mean haematocrit (p < 0.01) and in mean platelet volume (p < 0-001) over the six month period, but no change in either total platelet count or platelet distribution width in the patients with chronic renal fiilure receiving r-HuEPO. In contrast, both the control groups showed no significant change in MPV. Conclusions-The results suggest that r-HuEPO affects thrombopoiesis and may be part of a group of humoral factors contributing to megakaryocyte development and maturation. Larger platelets are more reactive and may contribute to the increased risk of thrombosis associated with r-HuEPO. The dose of r-HuEPO began at 50 IU/kg twice weekly (by subcutaneous injection), increasing to 75 IU/kg twice weekly after two to three months if there was an insufficient rise in haematocrit and haemoglobin. It is the policy of the renal unit to give aspirin to all patients starting r-HuEPO. Twelve out of the 78 patients did not receive aspirin during the six month period of study as they had been given r-HuEPO before the establishment of this policy.All the patients had a full blood count (in EDTA) measured on a Coulter STKS (Coulter Electronics, Northwell Drive, Luton, Beds) at monthly intervals from baseline (before starting r-HuEPO) up to six months. As a result of organisational procedure both within the renal wards and the haematology laboratory, most of the samples would have been analysed within 4 hours of venepuncture, but we cannot exclude a few samples having been analysed at a later time.The variables studied were haematocrit, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW).Changes in these variables were compared with baseline values and statistically analysed using Student's paired t test. A measure of the difference between the maximum value of a variable achieved over the six month period and baseline was calculated and used in the 159 on 7 May 2018 by guest. Protected by copyright.