Does Reinfusion of Stem Cell Products on Multiple Days Affect Engraftment?

Objective: High-doses of melphalan treatment with autologous stem cell transplantation in multiple myeloma (MM) remains a major treatment modality in suitable patients. A minimal dose of 2x106/kg CD34+ cells is preferred to achieve engraftment. Some patients need multiple leukapheresis procedures to achieve the necessary number of CD34+ cells, but this can cause a high volume of stem cell product that cannot be given in a single day. Whether or not the number of infusion days affects engraftment has not been studied before. We aimed to evaluate the impact of reinfusion of stem cells on multiple days on engraftment results. Materials and Methods: Demographic features, CD34+ cell doses, neutrophil and platelet engraftment days, hospitalization days, and number of infusion days of 149 autologous transplantations of 143 MM patients were evaluated retrospectively. Results: The data of 143 MM patients who were transplanted were analyzed retrospectively. Median age was 55±8.5 (range: 26-70) years with a male/female ratio of 91/58. Hospitalization days for all patients were 24±6 (range: 14-50) days. Mean CD34+ cell number was (7.5±5.3) x106/kg (range: 1.5-31x106/kg). CD34+ cells were reinfused in 1 day in 80.5% (n=120) of the patients, 2 days in 18.2% of the patients (n=27), and 3 days in 1.3% of the patients (n=2). For 29 patients, reinfusion was applied in more than 1 day because of the high volume of stem cell product. We did not see any dimethyl sulfoxide toxicity, cardiac arrhythmia, or volume overload complications. Hypertensive attacks during infusion were easily controlled by furosemide treatment. In the group with multiple infusions, the infused CD34+ cell numbers had a mean of (4.8±2.8)x106/kg, and in the single infusion group the mean was (8.1±5.5)x106/kg. There were no statistical differences between the two groups regarding platelet and neutrophil engraftment days (p=0.850, r=0.820 and p=0.500, r=0.440). There was no statistical difference between the two groups for hospitalization days (p=0.060, r=0.050). Conclusion: In cases with a high volume of stem cell product to acquire adequate stem cells, reinfusion can be safely applied across multiple days without any delay in engraftment

Traditional and novel cardiovascular risk factors in non-functioning adrenal adenomas.

Background: The majority of the incidentally discovered adrenal masses are non-functioning adrenal adenomas; however data regarding traditional and novel cardiovascular risk predictors in these subjects is lacking. The objective of our study was to investigate the levels of PAI-1, IL-6 and Apelin along with several traditional cardiovascular risk markers in subjects with non-functioning adrenal adenomas

The alteration of serum soluble CD40 ligand levels in overt and subclinical hypothyroidism

OBJECTIVE: There is controversy as to whether hypothyroidism increases cardiovascular risk. The effect of levothyroxine on the cardiovascular risk profile is also unclear. Recent studies suggest that there is evidence of inflammation and endothelial dysfunction in hypothyroidism. Soluble CD40 ligand (sCD40L) is a protein expressed mainly by activated platelets which have been found to be associated with cardiovascular events. The aim of our study was to investigate serum sCD40L levels and the effect of levothyroxine replacement on sCD40L levels in overt and subclinical hypothyroidism. DESIGN: We assessed lipid profile, serum sCD40L and hsCRP levels in 21 overt and 22 subclinical hypothyroid age-matched female patients with chronic autoimmune thyroiditis at baseline and one month after achieving euthyroidism by levothyroxine replacement, and compared them with the data from 22, age-matched, healthy controls. RESULTS: Overt and subclinical hypothyroid patients had decreased sCD40L levels compared to age-matched controls. The patients with subclinical hypothyroidism had slightly increased hsCRP levels, but the result was not statistically significant. In multiple regression analysis, FT3 and FT4 were found to be independent predictors of sCD40L levels. After levothyroxine replacement, serum sCD40L levels increased significantly in the patients with overt hypothyroidism. Although an increase was also observed in the subclinical hypothyroid group, it was not statistically significant. Levothyroxine replacement had no significant effect on hsCRP levels in the patients with overt hypothyroidism. However, the subjects with subclinical hypothyroidism showed a significant reduction in hsCRP levels after levothyroxine. CONCLUSION: The values of sCD40L and hsCRP in our study suggest that inflammatory pathways are complex and may be affected by different factors in hypothyroidism

The alteration of serum soluble CD40 ligand levels in overt and subclinical hypothyroidism.

OBJECTIVE: There is controversy as to whether hypothyroidism increases cardiovascular risk. The effect of levothyroxine on the cardiovascular risk profile is also unclear. Recent studies suggest that there is evidence of inflammation and endothelial dysfunction in hypothyroidism. Soluble CD40 ligand (sCD40L) is a protein expressed mainly by activated platelets which have been found to be associated with cardiovascular events. The aim of our study was to investigate serum sCD40L levels and the effect of levothyroxine replacement on sCD40L levels in overt and subclinical hypothyroidism. DESIGN: We assessed lipid profile, serum sCD40L and hsCRP levels in 21 overt and 22 subclinical hypothyroid age-matched female patients with chronic autoimmune thyroiditis at baseline and one month after achieving euthyroidism by levothyroxine replacement, and compared them with the data from 22, age-matched, healthy controls. RESULTS: Overt and subclinical hypothyroid patients had decreased sCD40L levels compared to age-matched controls. The patients with subclinical hypothyroidism had slightly increased hsCRP levels, but the result was not statistically significant. In multiple regression analysis, FT3 and FT4 were found to be independent predictors of sCD40L levels. After levothyroxine replacement, serum sCD40L levels increased significantly in the patients with overt hypothyroidism. Although an increase was also observed in the subclinical hypothyroid group, it was not statistically significant. Levothyroxine replacement had no significant effect on hsCRP levels in the patients with overt hypothyroidism. However, the subjects with subclinical hypothyroidism showed a significant reduction in hsCRP levels after levothyroxine. CONCLUSION: The values of sCD40L and hsCRP in our study suggest that inflammatory pathways are complex and may be affected by different factors in hypothyroidism

The evaluation of protein Z levels of children with acute lymphoblastic leukaemia during induction therapy

The objective of this study was to evaluate the protein Z levels of children with acute lymphoblastic leukaemia (ALL) during induction therapy. Although several studies investigated the association between steroid and L-asparaginase (L-ASP) administration and levels of coagulation proteins such as protein C, protein S and antithrombin in children with ALL, protein Z levels have not been examined in any study yet. Peripheral blood was drawn from the study group before chemotherapy (PZ0) at diagnosis, at 12th day (PZ1), 15th day (PZ2), 18th day (PZ3) and 21st day (PZ4) of treatment wherein L-ASP treatment is given along with steroid administration according to ALL BFM-1995 chemotherapy protocol. Plasma protein Z levels were measured by enzyme immunoassay method. Mean protein Z level at PZ0 was 1.628 +/- 0.485 mu g/ml in the study group and 1.672 +/- 0.662 mu g/ml in the control group. No statistical difference was observed. In the study group, there was a slight increase in protein Z levels between the PZ0 and PZ1 periods in which only steroid therapy was administered. Statistically significant decrease was observed between protein Z levels in PZ0 - PZ4, PZ1 - PZ2, PZ1 - PZ3, PZ1 - PZ4 and PZ3 - PZ4 periods. During the induction treatment, symptomatic haemorrhage or thrombosis was not followed up in any patients. We demonstrated that children with ALL have similar protein Z values to those of the control group at diagnosis. A significant decrease occurs at the end of the induction treatment with steroid and L-ASP administration. However, this deficiency does not result in development of symptomatic thrombosis or bleeding in these patients. (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

B-cell-activating factor, a proliferation inducing ligand and co-stimulatory molecules in the pathogenesis of immune thrombocytopenia in childhood

The aim of this study was to measure the levels of B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and co-stimulatory molecules in immune thrombocytopenia (ITP) of childhood to investigate the interaction between T and B lymphocytes and the impact of proliferation of B lymphocytes in the pathogenesis. Twenty newly diagnosed ITPs, 20 chronic ITPs, and 20 healthy controls between 2 and 18 years were enrolled in this study. Hemogram, BAFF, APRIL, interleukin-4, and interferon (IFN)-gamma levels in sera and expressions of CD19, CD 3, CD21, CD40, and CD 154 on leukocytes were measured by ELISA and flow cytometry. Mean BAFF level in newly diagnosed ITP group was higher than the mean BAFF level in other groups. BAFF levels were significantly decreased after the treatment in newly diagnosed ITP group. APRIL, interleukin-4, and IFN-gamma in newly diagnosed ITP group and BAFF, APRIL, interleukin-4, and IFN-gamma in chronic ITP group were similar before and after treatment. There was no statistical difference for expressions of CD 19 and CD3 on lymphocytes, CD40 on leukocytes, CD154 on T cells, and for percentages of CD21(+)/CD40(+), CD21(-)/CD40(+), CD21(+)/CD40(-) B cells, and CD19(-)/CD3(-) lymphocytes for pretreatment and posttreatment levels in both ITP groups. In conclusion, our study strongly demonstrated that BAFF has an important role in the pathogenesis of newly diagnosed childhood ITP. It may be important in the follow-up and in novel therapy modalities of these patients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabctic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets. (C) 2010 Elsevier Inc. All rights reserved

The Effect of the Acute Submaximal Exercise on Thrombin Activatable Fibrinolysis Inhibitor Levels in Young Sedentary Males

Depending on type, duration, and intensity of the exercise, changes occur in hemostasis. In this study, we evaluated the changes in the parameters of coagulation and fibrinolytic systems that happened after the submaximal aerobic exercises by bicycle ergomater. Twelve healthy male participants whose ages were between 21 and 28 have been included. The venous samples have been drawn before the exercise as well as at the 0th, 15th, and 60th minutes after the submaximal exercise. The values of prothrombin time (PT), active partial thromboplastin time (aPTT), D-dimer, fibrinogen, plasminogen activator inhibitor 1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) have been measured. Plasminogen activator inhibitor 1 values have shown an insignificant increase after exercise (P = .328), whereas, it has decreased significantly during the resting period (P = .033) Postexercise 15th and 60th minutes TAFI values have decreased significantly comparing to basal and postexercise (0th minute) values (P = .001). Fibrinolytic system activation is observed after acute submaximal aerobic exercise of sedentary healthy participants

Intraperitoneal and subcutaneous pharmacokinetics of low molecular weight heparin in continuous ambulatory peritoneal dialysis patients.

Today, low molecular weight heparins (LMWHs) are more and more commonly used. They are about to replace standard heparin in certain circumstances. The pharmacokinetics of intraperitoneal standard heparin are well known in continuous ambulatory peritoneal dialysis (CAPD), but data concerning LMWHs are lacking. The present study investigated the pharmacokinetics of intraperitoneal LMWHs in a single dose and compared them with the subcutaneous route in CAPD patients. The study enrolled 8 CAPD patients with a mean age of 47 +/- 14.14 years. All patients had 40 mg enoxaparin added to their night exchange on one day. Blood samples were drawn just before instillation and at 2, 4, 8, 12, 18, and 24 hours after instillation for determination of plasma antifactor Xa activity. After two days of washout, the same patients were given enoxaparin 40 mg subcutaneously, and blood samples were drawn at the same time points. Although no plasma factor Xa activity was seen after intraperitoneal administration, subcutaneous administration resulted in increased plasma factor Xa activity. We conclude that a single dose of intraperitoneal enoxaparin did not cause any change in plasma anti-factor Xa activity. That finding may be due either to an insufficient dose or to nonabsorption