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1.  Preventative Effects of Caffeic Acid Phenyl Ester on Cadmium Intoxication Induced Hematological and Blood Coagulation Disturbances and Hepatorenal Damage in Rats 
ISRN Hematology  2014;2014:764754.
The preventative effect of caffeic acid phenyl ester (CAPE) against hematological, blood coagulation, and hepatorenal disturbances in cadmium (Cd) intoxication was investigated in rats. Male Wistar rats were randomly assigned into control group, Cd-group, and Cd + CAPE group. Cd intoxication was induced by intraperitoneal injection (i.p.) of CdCl2 (1 mg/kg/day) for 21 days, and CAPE was daily given (10 micromol/kg; i.p.) for also 21 days. The results showed that Cd intoxication impaired hepatorenal function and significantly prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen level, red blood cells and platelets counts, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Interestingly, all these hematological, blood coagulation, and hepatorenal deteriorations of Cd toxicity were significantly prevented by CAPE. Additionally, CAPE significantly reversed the significant decreases in levels of total reduced glutathione and superoxide dismutase and increases in levels of thiobarbituric acid reactive substances that were observed in the sera and liver and kidney homogenates of Cd group. It is concluded that CAPE is a promising compound that can counteract the hematological and blood coagulation disturbances, oxidative stress, and hepatorenal damages in Cd intoxication. However, further studies are crucially needed to improve this treatment in patients.
doi:10.1155/2014/764754
PMCID: PMC4003892
2.  Relevant Aspects of Centrifugation Step in the Preparation of Platelet-Rich Plasma 
ISRN Hematology  2014;2014:176060.
Introduction. Platelet-Rich Plasma (PRP) is rich in growth factors, playing important role in tissue healing. The wide variation of reported protocols for preparation of PRP leads to variable compositions, which induce different biological responses and prevent results comparison. This study aims to highlight relevant aspects of the centrifugation step to obtain reproducible results and overall quality. Material and Methods. Samples of blood were collected from 20 healthy donors that have signed free informed consent. Two centrifugation steps (spins) were analyzed for the influence of centrifugal acceleration, time, processed volume, and platelet gradient. The Pure Platelet-Rich Plasma (P-PRP) was characterized as platelet concentration, integrity, and viability (sP-selectin measurement). Results. Lower centrifugal accelerations favour platelet separation. The processing of 3.5 mL of blood at 100 ×g for 10 min (1st spin), 400 ×g for 10 min (2nd spin), withdrawing 2/3 of remnant plasma, promoted high platelet recovery (70–80%) and concentration (5x) maintaining platelet integrity and viability. The recovery of platelets was reduced for a larger WB volume (8.5 mL) processed. Conclusion. Centrifugal acceleration, time, WB processed volume, and minimization of the platelet gradient before sampling are relevant aspects to ensure reproducible compositions within the autologous nature of PRP.
doi:10.1155/2014/176060
PMCID: PMC4005024
3.  Coexisting Iron Deficiency Anemia and Beta Thalassemia Trait: Effect of Iron Therapy on Red Cell Parameters and Hemoglobin Subtypes 
ISRN Hematology  2014;2014:293216.
Background. Coexistence of iron deficiency anemia (IDA) and beta thalassemia trait (BTT) has been the topic of few studies. However, no study from our country was found evaluating the effect of iron therapy in patients with concomitant IDA and BTT. Methods. Over a period of two years, 30 patients with concomitant IDA and BTT were included. All the patients had a complete blood count, serum iron studies, and thalassemia screening using BIORADTM hemoglobin testing system. The patients received oral iron therapy in appropriate dosages for a period of twenty weeks, after which all the investigations were repeated. Appropriate statistical methods were applied for comparison of pre- and posttherapy data. Results. All except two patients were adults with a marked female preponderance. Oral iron therapy led to statistically significant improvement in hemoglobin, red cell indices (P < 0.05), and marked change in serum iron, ferritin, and HbA2 levels (P < 0.001). There was a significant reduction in the total iron binding capacity levels. Conclusion. The present study shows the frequent occurrence of iron deficiency anemia in patients with beta thalassemia trait, which can potentially confound the diagnosis of the latter. Hence, iron deficiency should be identified and rectified in patients with suspicion of beta thalassemia trait.
doi:10.1155/2014/293216
PMCID: PMC3972954
4.  Prevalence of Deletional Alpha Thalassemia and Sickle Gene in a Tribal Dominated Malaria Endemic Area of Eastern India 
ISRN Hematology  2014;2014:745245.
Inherited hemoglobin disorders like alpha thalassemia and sickle gene are common in the Indian subcontinent. These disorders in the heterozygous state act as malaria resistance genes and influence the susceptibility to Plasmodium falciparum malaria. There is inadequate knowledge about the epidemiology of these malaria resistance genes in the tribal dominated malaria endemic region of the state of Odisha in eastern India. A cross sectional prevalence study was undertaken in 594 subjects in five tribal populations in this region, namely, Sahara (42.4%), Kutia Kandha (30.0%), Kuda (15.8%), Gond (9.8%), and Oraon (2.0%). Sickling test, Hb electrophoresis, HPLC, and molecular studies were undertaken to diagnose the prevalence of sickle allele, β-thalassemia allele, and deletional alpha thalassemia. Sickle and β thalassemia alleles were found in 13.1% and 3.4% of subjects, respectively. Sickle allele was found both in heterozygous (10.1%) and homozygous state (3.03%). The prevalence of alpha thalassemia was 50.84% with an allelic frequency of 0.37. Both α−3.7 and α−4.2 alpha thalassemia were detected with an allele frequency of 0.33 and 0.04, respectively. The high prevalence of alpha thalassemia and sickle gene in this population is probably due to selection pressure of endemic malaria in this part of India.
doi:10.1155/2014/745245
PMCID: PMC3967634  PMID: 24808962
5.  Pretransplant Comorbidities Maintain Their Impact on Allogeneic Stem Cell Transplantation Outcome 5 Years Posttransplant: A Retrospective Study in a Single German Institution  
ISRN Hematology  2014;2014:853435.
The introduction of reduced-intensity conditioning regimens has allowed elderly patients with preexisting comorbidities access to the potentially curative allogeneic stem cell transplantation. Patient's comorbidities at the time of treatment consideration play a significant role in transplant outcome in terms of both overall survival (OS) and nonrelapse mortality (NRM). The hematopoietic stem cell transplantation comorbidity index (HCT-CI) quantifies these patient specific risks and has established itself as a major tool in the pretransplant assessment of patients. Many single center and multicenter studies have assessed the HCT-CI score and reported conflicting outcomes. The present study aimed to evaluate the HCT-CI in a single large European transplant centre. 245 patients were retrospectively analyzed and the predictive value of the score was assessed with respect to OS and NRM. We confirm that the HCT-CI predicts outcome for both OS and NRM. Moreover, we identified age of the patient as an independent prognostic parameter for OS. Incorporation of age in the HCT-CI would improve its ability to prognosticate and allow the transplant physician to assess the patient specific risks appropriately at the time of counseling for transplant.
doi:10.1155/2014/853435
PMCID: PMC3963108  PMID: 24729881
6.  Oral and Dental Considerations in Pediatric Leukemic Patient 
ISRN Hematology  2014;2014:895721.
Throughout the world, there have been drastic decline in mortality rate in pediatric leukemic population due to early diagnosis and improvements in oncology treatment. The pediatric dentist plays an important role in the prevention, stabilization, and treatment of oral and dental problems that can compromise the child's health and quality of life during, and follow up of the cancer treatment. This manuscript discusses recommendations and promotes dental care of the pediatric leukemic patients.
doi:10.1155/2014/895721
PMCID: PMC3960739  PMID: 24724033
7.  Evaluation of the Utility of Thromboelastography in a Tertiary Trauma Care Centre 
ISRN Hematology  2014;2014:849626.
Background. Thromboelastography (TEG) unlike conventional coagulation assays evaluates the dynamic interaction of clotting factors and platelets indicating an overall clot quality. Literature assessing the efficacy of TEG in identifying trauma associated bleeding is lacking. Aim. To compare TEG with conventional plasma based coagulation tests and assess whether TEG can serve as a screening test or replace the conventional routine test. Materials. Retrospective data was collected for 150 severe trauma patients. Patients with known evidence of severe comorbidities, which may influence the outcome, were excluded. Detailed evaluation of the patient's clinical and laboratory records was conducted. Diagnostic characteristics such as sensitivity, specificity, and accuracy were calculated. Results. Fifty-one patients were defined as coagulopathic by the conventional coagulation test, 30 by the laboratory established range for TEG indices and 105 by manufactures range. Specificity and sensitivity for the laboratory established range for TEG were 29.4% and 84.8%; for manufactures range sensitivity was 74.5%, specificity was 32.3%. Conclusion. We observed that conventional coagulation assays are the most sensitive tests for diagnosis of coagulopathy due to trauma. However in emergency trauma situations, where immediate corrective measures need to be taken, coagulation parameters and conventional coagulation tests may cause delay. TEG can give highly specific results depicting the underlying coagulopathy.
doi:10.1155/2014/849626
PMCID: PMC3947774  PMID: 24695847
8.  The Problem of Anaemia in Patients with Colorectal Cancer 
ISRN Hematology  2014;2014:547914.
Background. Surgical patients are often anaemic preoperatively subsequently requiring blood transfusion. The aim of this study was to assess the problem of anaemia and transfusion rates in patients undergoing surgery for colorectal cancer. Methods. Haemoglobin levels and transfusion requirements were assessed retrospectively in 199 sequential patients operated on for colorectal cancer. This was followed by prospective analysis of 147 patients to correlate preoperative anaemia, stage of bowel cancer, and operation performed with rates of blood transfusion and length of hospital stay. Results. Preoperatively 44% patients were anaemic retrospectively and 60% prospectively. Anaemia increased the risk of transfusion in both studies (69% anaemic versus 31% nonanaemic, P = 0.002 in retrospective series, and 83.7% versus 16.3%, P < 0.0001 in prospective series). Anaemia was proportionally higher in patients with Dukes B (65.2%) and Dukes C (66.6%) than in patients with Dukes A (28.5%). Length of stay was prolonged in transfused patients excluding those requiring major blood transfusion (median 13 versus 7 days, P < 0.0001). Transfusion was also associated with higher mortality (P = 0.05). Conclusion. Anaemia is common in patients with colorectal cancer. Anaemic patients were at high risk of receiving blood transfusion, which in turn increased length of stay and mortality.
doi:10.1155/2014/547914
PMCID: PMC3947861  PMID: 24696785
9.  Association of Body Mass Index with Hemoglobin Concentration and Iron Parameters in Iranian Population 
ISRN Hematology  2014;2014:525312.
Background. Studies have reported that obesity has an adverse effect on iron metabolism. Obesity is characterized by chronic, low-grade, systemic inflammation and anemia of chronic disease with elevated serum ferritin and decreased level of serum iron, transferrin saturation, and hemoglobin. Therefore, we examined the association of body mass index with hemoglobin concentration and iron parameters in this study. Methods. This cross-sectional study was conducted in Yazd to assess the relation of body mass index with hemoglobin and iron parameters among 406 adult patients 18–65 years old. Diabetes and conditions that could influence body iron stores were excluded. Results. There is no difference in hemoglobin concentrations, MCV, serum iron, TIBC, transferrin saturation index, and ferritin between normal weight, overweight, and obese persons. Conclusion. Nutritional status of persons and intake of high iron foods by obese persons should be considered. Also, other inflammatory markers should be evaluated in the future studies.
doi:10.1155/2014/525312
PMCID: PMC3934448  PMID: 24665367
10.  Clinicohematological Study of Thrombocytosis in Children 
ISRN Hematology  2014;2014:389257.
Introduction. Primary thrombocytosis is very rare in children; reactive thrombocytosis is frequently observed in children with infections, anemia, and many other causes. Aims and Objectives. To identify the etiology of thrombocytosis in children and to analyze platelet indices (MPV, PDW, and PCT) in children with thrombocytosis. Study Design. A prospective observational study. Material and Methods. A total of 1000 patients with thrombocytosis (platelet > 400 × 109/L) were studied over a period of 2 years. Platelet distribution width (PDW), mean platelet volume (MPV), and plateletcrit (PCT) were noted. Results. Of 1000 patients, 99.8% had secondary thrombocytosis and only two children had primary thrombocytosis (chronic myeloid leukemia and acute myelogenous leukemia, M7). The majority of the children belonged to the age group of 1month to 2 years (39.7%) and male to female ratio was 1.6 : 1. Infection with anemia (48.3%) was the most common cause of secondary thrombocytosis followed by iron deficiency alone (17.2%) and infection alone (16.2%). Respiratory infection (28.3%) was the predominant infectious cause observed. Thrombocytosis was commonly associated with IDA among all causes of anemia and severity of thrombocytosis increased with severity of anemia (P = 0.021). With increasing platelet count, there was a decrease in MPV (<0.001). Platelet count and mean PDW among children with infection and anemia were significantly higher than those among children with infection alone and anemia alone. None were observed to have thromboembolic manifestations. Conclusions. Primary thrombocytosis is extremely rare in children than secondary thrombocytosis. Infections in association with anemia are most commonly associated with reactive thrombocytosis and severity of thrombocytosis increases with severity of anemia.
doi:10.1155/2014/389257
PMCID: PMC4004071
11.  Two Cases and Review of the Literature: Primary Percutaneous Angiography and Antiplatelet Management in Patients with Immune Thrombocytopenic Purpura 
ISRN Hematology  2013;2013:174659.
We report two cases of immune thrombocytopenic purpura (ITP) associated with acute coronary artery syndrome highlighting the interventions done in every case along with the medications used during intervention and as outpatient. The first case is that of a woman with ITP exacerbation while on dual antiplatelet therapy and the second case is that of a male presenting with non-ST elevation myocardial infarction (NSTEMI) while in a thrombocytopenic crisis. In both cases antiplatelet therapy was held and thrombopoietic therapy was initiated before resuming full anticoagulation and coronary intervention. Given the paucity of data on ITP and antiplatelets treatment in the setting of acute coronary syndrome, no strict recommendations can be proposed, but antiplatelets appear to be safe acutely and in the long term in this category of patients as long as few measures are undertaken to minimize the risks of bleeding and thrombosis.
doi:10.1155/2013/174659
PMCID: PMC3888679  PMID: 24459590
12.  Addition of Multimodal Therapy to Standard Management of Steady State Sickle Cell Disease 
ISRN Hematology  2013;2013:236374.
Most people on folic acid to boost erythropoiesis and prophylactic antimicrobials, the standard management of steady state sickle cell disease (SCD), have unacceptable numbers of crises. The objective of this study was to evaluate the effects of adding multimodal therapy with potassium thiocyanate and omega-3 fatty acids to the standard management of steady state SCD. Pre- and post-treatment numbers of crises and other disease indices were compared in 16 HbSS individuals on folic acid and paludrine after 12 months of adding eicosapentaenoic acid 15 mg/kg/day, docosahexaenoic acid 10 mg/kg/day, and potassium thiocyanate 1-2 mL/day, each milliliter of which contained 250 mg of thiocyanate and 100 micrograms of iodine to prevent hypothyroidism: a possible side-effect due to competitive inhibition of the transport of iodide into the thyroid gland by thiocyanate. Median number of crises reduced from 3/yr to 1/yr (P < 0.0001). There was no evidence of impaired thyroid function. Plasma level of tri-iodothyronine improved (P < 0.0001). Steady state full blood count and bilirubin level did not change significantly. The findings suggest that addition of potassium thiocyanate and eicosapentaenoic and docosahexaenoic acids to standard management of steady state SCD reduces the number of crises. This observation needs to be evaluated in larger studies.
doi:10.1155/2013/236374
PMCID: PMC3872154  PMID: 24386573
13.  Assessment of Regulatory T Cells in Childhood Immune Thrombocytopenic Purpura 
ISRN Hematology  2013;2013:143687.
This study had the objective to assess the frequency of Tregs in children newly diagnosed with ITP and ascertain whether an association exists between Tregs and platelet counts, by means of a comparison with healthy controls. This case-control study included 19 patients newly diagnosed with ITP—whose blood samples were collected at four points in time: before any therapy and 1, 3, and 6 months after diagnosis—and 19 healthy controls. Tregs (CD4+ CD25+Foxp3 T cells) were evaluated by flow cytometry. There was a statistically significant difference in platelet count between the case and control groups. There were no significant differences in Treg counts between cases and controls at any point during the course of the study and no difference in Treg counts between the chronic and nonchronic groups and no significant correlation between Tregs and platelet counts in the case and control groups. The findings of this study did not show any statistically significant correlation between Tregs and number of platelets in the case and control groups. Treg cells did not play a role in the regulation of autoimmunity in children with ITP.
doi:10.1155/2013/143687
PMCID: PMC3835721  PMID: 24298390
14.  Survival and Prognostic Factors for AIDS and Non-AIDS Patients with Non-Hodgkin's Lymphoma in Bahia, Brazil: A Retrospective Cohort Study 
ISRN Hematology  2013;2013:904201.
Despite the benefits of HAART, HIV-infected patients are increasingly affected by different malignancies. We compared a 5-year-period survival time and prognostic factors for HIV-1-infected individuals diagnosed with non-Hodgkin lymphomas (NHL) in a nested case-control study, with non-HIV-infected individuals in Salvador, Brazil. Survival time and prognostic factors were compared to HIV-negative patients. 31 cases (versus 63 controls) had a significantly more advanced NHL at diagnosis and lower mean CD4 count (26 cells/mm3) than controls. Mean overall survival (OS) was 35.8 versus 75.4 months, for cases and controls, respectively (P < 0.001), while mean event-free survival time (EFS) was 34.5 months for cases, versus 68.8 for controls (P = 0.002). Higher IPI, increased LDH levels, bone marrow infiltration, lower absolute lymphocyte counts (<1,000 cells/mm3), and type B symptoms were associated with a shorter survival time for cases. Although patients without poorer prognostic factors at baseline had an OS comparable to controls, the mean CD4 cell count for cases was similar for patients with favorable and nonfavorable response to therapy. Our findings suggest that HIV-1 infection is significantly associated with a shorter survival time for patients with NHL, independently of other predictive factors and of disease stage.
doi:10.1155/2013/904201
PMCID: PMC3830808  PMID: 24288620
15.  Interaction of Normal and Sickle Hemoglobins for Sodium Dodecylsulphate and Hydrogen Peroxide at pH 5.0 and 7.2 
ISRN Hematology  2013;2013:629640.
Clinical manifestations of malaria primarily result from proliferation of the parasite within the hosts' erythrocytes. The malaria parasite digests hemoglobin within its digestive vacuole through a sequential metabolic process involving multiple proteases. The activities of these proteases could lead to the production of ROS which could lead to the death of the parasites due to the destruction of their membrane. The action of SDS on hemoglobins can be likened to the way malarial proteases destabilizes host hemoglobin. Hence, the study was designed to determine the binding parameters of SDS and H2O2 for normal, sickle trait carrier and sickle hemoglobins at pH 5.0 and 7.2 using UV-VIS Titration Spectrophotometry. Hb-SDS interactions were significantly different at pH 5.0 but were not at pH 7.2. Also, Hb-H2O2 interactions were statistically different at pH 5.0 and 7.2. The interactions suggest that HbA and HbS are easily destabilized than HbAS and that HbAS has more affinity for H2O2. These suggest a production of more ferryl intermediates or hydroxyl radicals. All these interactions may hinder the development of the malaria parasite at the intraerythrocytic stage and could likely account for a significant proportion of the mechanism that favours the resistance to malaria by individuals with HbAS.
doi:10.1155/2013/629640
PMCID: PMC3810493  PMID: 24224093
16.  The Modern Primitives: Applying New Technological Approaches to Explore the Biology of the Earliest Red Blood Cells 
ISRN Hematology  2013;2013:568928.
One of the most critical stages in mammalian embryogenesis is the independent production of the embryo's own circulating, functional red blood cells. Correspondingly, erythrocytes are the first cell type to become functionally mature during embryogenesis. Failure to achieve this invariably leads to in utero lethality. The recent application of technologies such as transcriptome analysis, flow cytometry, mutant embryo analysis, and transgenic fluorescent gene expression reporter systems has shed new light on the distinct erythroid lineages that arise early in development. Here, I will describe the similarities and differences between the distinct erythroid populations that must form for the embryo to survive. While much of the focus of this review will be the poorly understood primitive erythroid lineage, a discussion of other erythroid and hematopoietic lineages, as well as the cell types making up the different niches that give rise to these lineages, is essential for presenting an appropriate developmental context of these cells.
doi:10.1155/2013/568928
PMCID: PMC3814094  PMID: 24222861
17.  Portal Hypertension and Myeloproliferative Neoplasms: A Relationship Revealed 
ISRN Hematology  2013;2013:673781.
Background/Objectives. Patients with myeloproliferative neoplasms have a well-established increased risk of thrombosis. Many trials report identification of an underlying myeloproliferative neoplasm by investigation of the patients developing portal hypertensive esophagus and/or fundus variceal hemorrhage in the absence of any known etiology. This trial was designed to investigate the association between myeloproliferative neoplasms and portal hypertension and to detect the frequency of portal hypertension development in this subset of patients. Methodology. Twenty-nine patients previously diagnosed with polycythemia vera, essential thrombocytopenia, and primary myelofibrosis, who were under followup at the hematology outpatient clinic of our hospital, were included in the trial. Results. In our trial, we detected portal hypertension in 13.8% of the patients (n = 4), as a finding that was similar to those obtained in other studies performed to date. Conclusions. Considering the fact that diagnosis of myeloproliferative neoplasms usually takes a long time, treatment should be started (while, on the other hand, assessing the investigational and therapeutical choices for the complications) right after the bone marrow biopsy or cytogenetic studies required for establishing the final diagnosis have been performed.
doi:10.1155/2013/673781
PMCID: PMC3789477  PMID: 24159391
18.  Waldenström Macroglobulinemia: Clinical and Immunological Aspects, Natural History, Cell of Origin, and Emerging Mouse Models 
ISRN Hematology  2013;2013:815325.
Waldenström macroglobulinemia (WM) is a rare and currently incurable neoplasm of IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function mutation in the MYD88 adapter protein. This not only provides an intriguing link to new findings that natural effector IgM+IgD+ memory B-cells are dependent on MYD88 signaling, but also supports the hypothesis that WM derives from primitive, innate-like B-cells, such as marginal zone and B1 B-cells. Following a brief review of the clinical aspects and natural history of WM, this review discusses the thorny issue of WM's cell of origin in greater depth. Also included are emerging, genetically engineered mouse models of human WM that may enhance our understanding of the biologic and genetic underpinnings of the disease and facilitate the design and testing of new approaches to treat and prevent WM more effectively.
doi:10.1155/2013/815325
PMCID: PMC3782845  PMID: 24106612
19.  HBsAg Positive Patient Characteristics in Hospital and Blood Donation Camps 
ISRN Hematology  2013;2013:675191.
Background. Prevention of the residual risk of transfusion transmitted hepatitis B virus infection (HBV) is mostly dependant on serological screening of blood donors for HBsAg and antibody to hepatitis B core antigen (anti-HBc Ab). This study aimed to study the prevalence of HBsAg and anti-HBc Ab and to compare the profile of blood donors attending a blood donation camp and people attending a hospital based camp. Methods. In the blood donor camp, all the blood units were screened for HBV, (HBsAg and anti-HBc), and in the hospital based camp, screening was done for HBsAg alone. Baseline demographic characteristics were noted. Results. The number of blood bank donors was 363 (47.5%) and hospital camp attendees was 402 (52.5%). Prevalence of HBsAg positivity was similar in both the groups at 1.7% and 1.9%, respectively. Anti-HBc Ab positivity (Total) was 6% among the blood donors; Overall prevalence of HBV infection in this group was 3.2%. Conclusion. Policy for checking the collected blood unit by 3 tests for anti-HBc, anti-HBsAb, and HBsAg should be reconsidered to possibly achieve the zero risk goal of transfusion transmitted HBV infection. Blood obtained from a vaccinated donor may give an added protection to the recipient.
doi:10.1155/2013/675191
PMCID: PMC3777120  PMID: 24083029
20.  Detailed Analysis of Diffuse Large B Cell Lymphoma Patients: A Single-Center, Retrospective Study 
ISRN Hematology  2013;2013:908191.
The aim of this single-center, retrospective study was to investigate the impact of rituximab, reconsider the validity of International Prognostic Index (IPI), and evaluate the prognostic role of the cell of origin (CoO) in a relatively young cohort. Three hundred twelve diffuse large B cell lymphoma patients (median age: 52) were included. Rituximab significantly improved the 3- and 5-year progression free survival (PFS) (70% versus 65% and 41% versus 36%, resp.; P < 0.001) but led only to a slight, insignificant increase in 3- and 5-year overall survival (OS) (71% versus 77.3% and %67 versus 74.5%, resp.; P = 0.264). In the young, low risk patient subgroup (aaIPI = 0&1; n = 129), rituximab improved 3- and 5-year PFS and OS rates (P < 0.001 and P = 0.048, resp.). The efficacy of rituximab in young high risk patients was comparable to the literature. CoO data were available in 190 patients. The OS at 3 years was 79% for GC and 64% for non-GC subgroups (P = 0.014). To the best of our knowledge, this is the first study which investigated the impact of R-CHOP in the context of CoO and IPI in a relatively young cohort. CoO was not an independent risk factor for prognosis in the multivariate analysis although patients with GC showed a significant survival advantage in the univariate analysis. CoO was also found to be a significant determinant of response in refractory/relapsed patients. Our results confirm the efficacy of rituximab in low and high risk, young patients outside of a randomized clinical trial setting.
doi:10.1155/2013/908191
PMCID: PMC3747433  PMID: 23984080
21.  Frequency and Outcome of Graft versus Host Disease after Stem Cell Transplantation: A Six-Year Experience from a Tertiary Care Center in Pakistan 
ISRN Hematology  2013;2013:232519.
Objective. The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan. Materials and Methods. Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 μg twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15 mg/m2 on day +1 followed by 10 mg/m2 on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification. Results. A total of 153 transplants were done from April 2004 to December 2011. Out of these were allogeneic transplants. There were females and males. The overall frequency of any degree of graft versus host disease was 34%. Acute GvHD was present in patients while had chronic GvHD. Grade II GvHD was present in patients while grade III and IV GvHD was seen in patients each. Acute myeloid leukemia and chronic myeloid leukemia were most commonly associated with GvHD. The mortality in acute and chronic GvHD was 8.8% and 12% respectively. Conclusion. The frequency of graft versus host disease in this study was 34% which is lower compared to international literature. The decreased incidence can be attributed to reduced diversity of histocompatibility antigens in our population.
doi:10.1155/2013/232519
PMCID: PMC3712246  PMID: 23936661
22.  Bacteriological Safety of Blood Collected for Transfusion at University of Gondar Hospital Blood Bank, Northwest Ethiopia 
ISRN Hematology  2013;2013:308204.
Background. Transfusion associated bacterial infection has remained more frequent with a sever risk of morbidity and mortality. This study assessed the bacteriological safety of blood collected for transfusion. Method. A cross-sectional study was conducted at University of Gondar hospital blood bank from December 2011 to June 2012. Bacterial isolation, identification, and antimicrobial susceptibility tests were done as per the standard procedure. Chi-square test and P value were used to assess associations between risk factors and the bacterial isolation rate. Results. Twenty-one (15.33%) blood units were found contaminated with bacteria, and 95.24% contamination was due to external sources. The commonly isolated bacteria were Staphylococcus aureus, Coagulase negative Staphylococci, Escherichia coli, Klebsiella species, Streptococci species, Enterobacter species, and Citrobacter species. All of the bacteria isolated were 100% sensitive to Gentamicin, Chloramphenicol, Amoxicillin, and Doxycycline. Multiple antimicrobial resistances were observed in 66.7% of the isolates. Not using glove by phlebotomist, touching disinfected phlebotomy site and double puncture at the same hand or both hands of a donor were found to be risk factors for bacterial contamination. Conclusion. Bacterial contamination of blood to be transfused is a common problem in the hospital. So attention should be given to activities performed at the blood bank for safe transfusion practices.
doi:10.1155/2013/308204
PMCID: PMC3705748  PMID: 23864956
23.  Detection of Minimal Residual Disease by Flow Cytometry for Patients with Multiple Myeloma Submitted to Autologous Hematopoietic Stem Cell Transplantation 
ISRN Hematology  2013;2013:847672.
The treatment strategy in multiple myeloma (MM) is to get complete remission followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45−/dim, CD38+high, CD138+, CD19−, and  CD56+high in most cases. The description of this immunophenotype is of major importance as it leads to the correct identification of minimal residual disease (MRD). Samples from 44 Patients were analyzed prospectively in this study. We analyzed if the presence of MRD at three months after HSCT was predictive of relapse or death. There were 40 evaluable patients of whom 16/40 patients had MRD at three moths after HSCT and there were none in cytological relapse. The mean overall survival (OS) was 34 months and disease-free survival (RFS) was 28 months after HSCT. There was no significant difference in the log rank analysis comparing OS and the presence of MRD (P = 0,611) and RFS (P = 0,3106). Here, we demonstrate that three color flow cytometry (FCM) is more sensitive for MDR evaluation than cytological analyzes. However, based in our data we can not affirm that MRD is a good predictor of MM relapse or death. In conclusion, our results could be attributed to a short followup, small sample size, and over most to the inability of a three-color FCM to detect the NPC population.
doi:10.1155/2013/847672
PMCID: PMC3705753  PMID: 23864957
24.  Expression Level of IL-6 Secreted by Bone Marrow Stromal Cells in Mice with Aplastic Anemia 
ISRN Hematology  2013;2013:986219.
Parasecretion of the hematopoietic cytokines is considered as one of the mechanisms account for bone marrow hematopoiesis disorder. In this study, the level of IL-6 secreted by bone marrow stromal cells from a mouse model of aplastic anemia was analyzed. The aplastic anemia mouse model was established with cyclophosphamide in combination with chloramphenicol and 60Coγ radiation. The impairment of bone marrow hematopoiesis induced by irradiation and chemotherapeutic drugs was subsequently characterized by peripheral blood cell count, pathomorphological changes, and apoptosis rate. Furthermore, the in vitro proliferation of bone marrow stromal cells (BMSC) and the IL-6 secretion levels of BMSC were analyzed. In our model of aplastic anemia, the number of peripheral blood cells and bone marrow cells (BMC) were notably decreased, and the apoptosis rate of BMC increased. Furthermore, the proliferation of BMSC was obviously impeded while the IL-6 secretion levels of BMSC significantly increased. The findings of our study suggested that the IL-6 secretion level may be enhanced to some extent by the induction of aplastic anemia caused by irradiation and chemotherapeutic drugs and that the abnormal level of IL-6 might probably interfere with the stability of the bone marrow hematopoietic microenvironment.
doi:10.1155/2013/986219
PMCID: PMC3703356  PMID: 23853724
25.  Hematological and Genetic Predictors of Daytime Hemoglobin Saturation in Tanzanian Children with and without Sickle Cell Anemia 
ISRN Hematology  2013;2013:472909.
Low hemoglobin oxygen saturation (SpO2) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO2 in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO2 was 97% (IQ range 94–99%) in SCA (N = 458), lower (P < 0.0001) than non-SCA (median 99%, IQ range 98–100%; N = 394). Within SCA, associations with SpO2 were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (P < 0.001, Adj r2 = 0.09). In non-SCA only age correlated with SpO2. α-thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient −0.60, P < 0.0001). In multivariable models, lower SpO2 correlated with higher MCH (β-coefficient −0.32, P < 0.001) or with decreased copies of α-thalassemia 3.7 deletion (β-coefficient 1.1, P < 0.001), and independently in both models with lower HbF% (β-coefficient 0.15, P < 0.001) and Glucose-6-Phosphate Dehydrogenase genotype (β-coefficient −1.12, P = 0.012). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO2 in children with SCA. Potential mechanisms and implications are discussed.
doi:10.1155/2013/472909
PMCID: PMC3649307  PMID: 23691341

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