Kadir Acar

Factors affecting stem cell mobilization for autologous hematopoietic stem cell transplantation.

High‐dose chemotherapy with autologous stem cell transplantation (ASCT) is curative treatment in various hematologic malignancies. Mobilization and collection of peripheral blood stem cell is the essential part of ASCT. The aim of this study was to evaluate the effectiveness of various mobilization regimens, determine the risk factors associated with mobilization failure (MF). We also investigated whether iron overload, which has an adverse impact on various aspects of HSCT including overall survival had any impact on mobilization kinetics. A total of 118 consecutive patients were included in this study. The rate of MF was 11.8 % with the first mobilization regimen. Frequency of MF was higher in lymphoma (P < 0.001) patients and in those receiving G‐CSF alone (P= 0.01). Peripheral CD34+ cell count (P < 0.001), bone marrow cellularity (P < 0.001), reticulin fibrosis (P < 0.05) were significantly lower whereas serum ferritin levels (P = 0.06) tended to be higher in patients with MF. CD34+ cell count of the first apheresis product was positively correlated with the white blood cell count (P < 0.05; r = 0.232), platelet count (P = 0.01; r = 0.233), peripheral CD34+ cell count (P < 0.001; r = 0.704) and the grade of bone marrow reticulin fibrosis (P < 0.001; r = 0.366). Serum ferritin levels were negatively correlated with maximum peripheral CD34+ cell count (P = 0.02; r = −0.216) and the CD34+ cell count in the first product (P = 0.05; r = −0.183). Platelet count (P = 0.03; β = 0.262), peripheral CD34+ cell count (P = 0.02; β=0.279) were the two variables which remained to be significant in multivariate analysis. Predicting the poor mobilizers with the platelet count for instance may reduce the risk of MF by using more effective regimens in advance. J. Clin. Apheresis, 2010.

Haemostatic role and histopathological effects of a new haemostatic agent in a rat bladder haemorrhage model: an experimental trial

To investigate the haemostatic efficacy and histopathological effects of a new haemostatic agent, Ankaferd BloodStopper® (ABS; Ankaferd Drug Cosmetic Co., Istanbul, Turkey) in a rat bladder haemorrhage model. ABS is a unique combination of five plant extracts that has been used in Turkish traditional medicine as a haemostatic agent for external traumatic bleeds.

Serum transforming growth factor-beta levels in patients with vitamin D deficiency

BACKGROUND Transforming growth factor-beta 1 (TGF-β1) contributes to tissue repair by promoting tissue fibrosis, and elevations have been reported in patients with bone marrow fibrosis. The aim of this study was to evaluate the relationship between TGF-β1 levels and vitamin D deficiency. METHODS All patients presenting to the outpatient Endocrinology and Metabolic Diseases clinic between June and September of 2008 were approached, and consenting patients who were deemed suitable candidates were enrolled. Hematological parameters were measured, along with serum levels of total and ionized calcium, phosphorus, parathyroid hormone, iron, folic acid vitamin B12 levels, 25 OH vitamin D3 (25OHD(3)) and TGF-β1. RESULTS A total of 132 patients were included in the study. Patients were divided into 4 groups based on levels of 25OHD(3) [group 1 (<5 ng/ml), 20 patients; group 2 (5-15 ng/ml), 38 patients; group 3 (16-30 ng/ml); and group 4 (>30 ng/ml), 28 patients]. TGF-β1 levels were higher in patients in group 1 compared to the other groups. Transforming growth factor-beta levels correlated negatively with vitamin D3 and positively with leukocyte count, platelet count, of MCV and MCH. Multiple regression analyses revealed TGF-β1 levels to be associated with 25OHD(3) as well as with platelet count. CONCLUSIONS Results of this study are suggestive of the presence of a significant relationship between TGF-β and vitamin D deficiency. Increased TGF-β1 and platelet count may be an early indicator of bone marrow fibrosis in patients with vitamin D deficiency.

Increased global fibrinolytic capacity as a clue for activated fibrinolysis in pre-eclampsia.

The aim of this study was to compare fibrinolysis in normal pregnancy and pre-eclampsia using individual markers of thrombosis and fibrinolysis with the contribution of a new parameter, global fibrinolytic capacity. Coagulation was determined with thrombin–antithrombin complex and prothrombin fragment 1+2 (F 1+2) and fibrinolysis markers. Tissue plasminogen activator, plasminogen activator inhibitor-1 and global fibrinolytic capacity were determined in 14 normal pregnancies and 29 women with pre-eclampsia. global fibrinolytic capacity was also determined in 14 age-matched healthy women. The Mann–Whitney U test and Pearson correlation test were used for statistical analysis. Thrombin–antithrombin complex, prothrombin fragment 1+2 levels, and global fibrinolytic capacity levels in pre-eclamptic women were significantly higher than in women with normal pregnancies (P < 0.05). Tissue plasminogen activator, plasminogen activator inhibitor-1 levels were also significantly higher in the pre-eclampsia group (P < 0.001 and P < 0.05 respectively). No significant correlation was found between global fibrinolytic capacity and thrombin–antithrombin complex, prothrombin fragment 1+2 levels, tissue plasminogen activator or plasminogen activator inhibitor-1 activity. Our results suggest that both thrombin formation and fibrinolysis are increased in pre-eclampsia compared with normal pregnancy. The increased global fibrinolytic capacity indicates that fibrinolysis remains preserved in pre-eclampsia. We suggest that global fibrinolytic capacity may be a useful parameter for accurately measuring in-vivo fibrinolysis globally, instead of with single parameters which may overlook the complex interactions between coagulation and fibrinolytic systems.

Renin-angiotensin system expression in the K562 human erythroleukaemic cell line:

Local renin-angiotensin system (RAS) may affect leukaemic cell production within the bone marrow microenvironment.Angiotensin-converting enzyme (ACE), renin, and angiotensin could influence leukaemogenesis. In this study, mRNA expressions of the major RAS components (ACE, renin, and angiotensinogen) in K562 human erythroleukaemia cell line have been searched by Real Time quantitative polymerase chain reaction. K562 blasts are multipotential, haematopoietic malignant cells that spontaneously differentiate into recognisable progenitors of the erythrocyte, granulocyte and monocytic series.We observed significant expressions of ACE, renin, and angiotensinogen in K562 leukaemic blast cells.Therefore, K562 human erythroleukaemia cell line may serve as an in vitro model to elucidate the role of RAS in leukaemia and to test the effects of RAS-affecting drugs on leukaemic cellular proliferation.

The intensive care management process in patients with hematopoietic stem cell transplantation and factors affecting their prognosis

Abstract Objectives Hematopoietic stem cell transplantation (HSCT) recipients may require further management in intensive care unit (ICU). The ICU outcome of the HSCT recipients is claimed to have improved significantly over the last two decades. Our aim was to investigate the ICU outcome of the HSCT recipients who required management in ICU, together with the factors that are likely to affect the results. Materials and methods We retrospectively investigated the ICU outcome of 48 adults (≥18 years of age) who received HSCT in the bone marrow transplant unit of our hospital and required admission to ICU between 01 January 2007 and 31 December 2010. The data were retrieved from the databases of the adult bone marrow transplantation unit and the ICU. Results Sixty-one percent of the patients were male with a median age of 39 years (28–46.75) in the study cohort. Leukemia (54%) and lymphoma (27%) were the leading underlying disorders. The type of HSCT was autologous in 14.6% and allogeneic in 85.4% of the patients. The reason for admission to ICU was acute respiratory failure in 85.5% of the HSCT recipients and 75% had sepsis/septic shock. The mean duration of ICU stay was 104.5 (48–168) hours. Sixty-nine percent of the patients died during their ICU stay while 31% survived. Besides the several statistically significant differences between the patients who survived or died in ICU in univariate analysis, baseline Acute Physiology and Chronic Health Evaluation (APACHE II) score (odds ratio 1.38, 95% confidence interval: 1.06–1.79) and requirement of vasopressors in the ICU (odds ratio 72.29, 95% confidence interval:4.47–1169.91) were found to be independent risk factors for mortality in multivariate analysis. Conclusion Baseline APACHE II score and requirement of vasopressors during ICU stay were the most significant independent risk factors for mortality in HSCT recipients who required ICU management in our center.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

The Association between Myocardial Iron Load and Ventricular Repolarization Parameters in Asymptomatic Beta-Thalassemia Patients

Previous studies have demonstrated impaired ventricular repolarization in patients with β-TM. However, the effect of iron overload with cardiac T2* magnetic resonance imaging (MRI) on cardiac repolarization remains unclear yet. We aimed to examine relationship between repolarization parameters and iron loading using cardiac T2* MRI in asymptomatic β-TM patients. Twenty-two β-TM patients and 22 age- and gender-matched healthy controls were enrolled to the study. From the 12-lead surface electrocardiography, regional and transmyocardial repolarization parameters were evaluated manually by two experienced cardiologists. All patients were also undergone MRI for cardiac T2* evaluation. Cardiac T2* score <20 msec was considered as iron overload status. Of the QT parameters, QT duration, corrected QT interval, and QT peak duration were significantly longer in the β-TM group compared to the healthy controls. T p − T e and T p − T e dispersions were also significantly prolonged in β-TM group compared to healthy controls. (T p − T e)/QT was similar between groups. There was no correlation between repolarization parameters and cardiac T2* MRI values. In conclusion, although repolarization parameters were prolonged in asymptomatic β-TM patients compared with control, we could not find any relation between ECG findings and cardiac iron load.

Pro-oxidative/antioxidative imbalance: a key indicator of adverse outcome in hematopoietic stem cell transplantation.

Introduction:  Pretransplantation iron overload (IO) is considered as a predictor of adverse outcome in hematopoietic stem cell transplantation (HSCT). Peroxidative tissue injury caused by IO leads to progressive organ dysfunction.

Outcome of pregnancies in women with thrombophilic disorders

Women with thrombophilic disorders may have pregnancy complications including fetal loss (FL); however, the impact of thromboprophylaxis with low molecular weight heparin (LMWH) and previous obstetric history remains to be clarified. Our aim was to compare the effects of LMWH in three groups of women with thrombophilia who had varying numbers of prior fetal losses. We prospectively investigated the live birth rates in 66 women with thrombophilic conditions, treated with a LMWH (enoxaparin, 40 mg daily). Groups 1, 2 and 3 included patients with 0–1, 2–3 and ≥4 pregnancy losses, respectively. Groups 1, 2 and 3 had 90.47%, 83.78% and 50.00% live birth frequencies, respectively. Group 3 had a significantly lower chance of a live birth compared with Group 1, regardless of type of thrombophilic disorder. FL aetiology in thrombophilic patients with multiple miscarriages appears multifactorial, and thromboprophylaxis alone may not be sufficient.