Advances in Hematology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Influence of Oxidative Stress on Stored Platelets Tue, 02 Feb 2016 07:27:19 +0000 Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS) is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platelets were stored for 12 days at 22°C. OS markers such as aggregation, superoxides, reactive oxygen species, glucose, pH, lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed. OS increased during storage as indicated by increments in aggregation, superoxides, pH, conjugate dienes, and superoxide dismutase and decrements in glucose and catalase. Thus, platelets could endure OS till 6 days during storage, due to the antioxidant defense system. An evident increase in OS was observed from day 8 of storage, which can diminish the platelet efficacy. The present study provides an insight into the gradual changes occurring during platelet storage. This lays the foundation towards new possibilities of employing various antioxidants as additives in storage solutions. K. Manasa and R. Vani Copyright © 2016 K. Manasa and R. Vani. All rights reserved. Haploidentical Hematopoietic Stem Cell Transplantation: Expanding the Horizon for Hematologic Disorders Tue, 02 Feb 2016 07:22:40 +0000 Despite the advent of targeted therapies and novel agents, allogeneic hematopoietic stem cell transplantation remains the only curative modality in the management of hematologic disorders. The necessity to find an HLA-matched related donor is a major obstacle that compromises the widespread application and development of this field. Matched unrelated donors and umbilical cord blood have emerged as alternative sources of donor stem cells; however, the cost of maintaining donor registries and cord blood banks is very high and even impractical in developing countries. Almost every patient has an HLA haploidentical relative in the family, meaning that haploidentical donors are potential sources of stem cells, especially in situations where cord blood or matched unrelated donors are not easily available. Due to the high rates of graft failure and graft-versus-host disease, haploidentical transplant was not considered a feasible option up until the late 20th century, when strategies such as “megadose stem cell infusions” and posttransplantation immunosuppression with cyclophosphamide showed the ability to overcome the HLA disparity barrier and significantly improve the rates of engraftment and reduce the incidence and severity of graft-versus-host disease. Newer technologies of graft manipulation have also yielded the same effects in addition to preserving the antileukemic cells in the donor graft. Mohammad Faizan Zahid and David Alan Rizzieri Copyright © 2016 Mohammad Faizan Zahid and David Alan Rizzieri. All rights reserved. Donor Specific Anti-HLA Antibody and Risk of Graft Failure in Haploidentical Stem Cell Transplantation Sun, 24 Jan 2016 14:12:51 +0000 Outcomes of allogeneic hematopoietic stem cell transplantation (AHSCT) using HLA-half matched related donors (haploidentical) have recently improved due to better control of alloreactive reactions in both graft-versus-host and host-versus-graft directions. The recognition of the role of humoral rejection in the development of primary graft failure in this setting has broadened our understanding about causes of engraftment failure in these patients, helped us better select donors for patients in need of AHSCT, and developed rational therapeutic measures for HLA sensitized patients to prevent this unfortunate event, which is usually associated with a very high mortality rate. With these recent advances the rate of graft failure in haploidentical transplantation has decreased to less than 5%. Piyanuch Kongtim, Kai Cao, and Stefan O. Ciurea Copyright © 2016 Piyanuch Kongtim et al. All rights reserved. Myeloablative Conditioning with PBSC Grafts for T Cell-Replete Haploidentical Donor Transplantation Using Posttransplant Cyclophosphamide Thu, 21 Jan 2016 06:51:10 +0000 Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based () and a TBI-based MA preparative regimen (), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation. Scott R. Solomon, Melhem Solh, Lawrence E. Morris, H. Kent Holland, and Asad Bashey Copyright © 2016 Scott R. Solomon et al. All rights reserved. Comparison of Bone Mineral Density in Thalassemia Major Patients with Healthy Controls Thu, 31 Dec 2015 06:51:56 +0000 Chronic hemoglobinopathies like thalassemia are associated with many osteopathies like osteoporosis. Methods. This observational study was carried out to compare the bone mineral density (BMD) in transfusion dependent thalassemics with that of healthy controls. Thirty-two thalassemia patients, aged 2–18 years, and 32 age and sex matched controls were studied. The bone mineral concentration (BMC) and BMD were assessed at lumbar spine, distal radius, and neck of femur. Biochemical parameters like serum calcium and vitamin D levels were also assessed. Results. The BMC of neck of femur was significantly low in cases in comparison to controls. We also observed significantly lower BMD at the lumbar spine in cases in comparison to controls. A significantly positive correlation was observed between serum calcium levels and BMD at neck of femur. Conclusion. Hence, low serum calcium may be used as a predictor of low BMD especially in populations where incidence of hypovitaminosis D is very high. Mahesh Chand Meena, Alok Hemal, Mukul Satija, Shilpa Khanna Arora, and Shahina Bano Copyright © 2015 Mahesh Chand Meena et al. All rights reserved. Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive Leukemias Wed, 30 Dec 2015 13:52:42 +0000 BCR-ABL-mediated leukemias, either Chronic Myeloid Leukemia (CML) or Philadelphia positive Acute Lymphoblastic Leukemia (ALL), are the paradigm of targeted molecular therapy of cancer due to the impressive clinical responses obtained with BCR-ABL specific tyrosine kinase inhibitors (TKIs). However, BCR-ABL TKIs do not allow completely eradicating both CML and ALL. Furthermore, ALL therapy is associated with much worse responses to TKIs than those observed in CML. The identification of additional pathways that mediate BCR-ABL leukemogenesis is indeed mandatory to achieve synthetic lethality together with TKI. Here, we review the role of BCR-ABL/protein kinase CK2 interaction in BCR-ABL leukemias, with potentially relevant implications for therapy. Alessandro Morotti, Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Riccardo Taulli, Angelo Guerrasio, and Giuseppe Saglio Copyright © 2015 Alessandro Morotti et al. All rights reserved. Comparable Outcomes for Hematologic Malignancies after HLA-Haploidentical Transplantation with Posttransplantation Cyclophosphamide and HLA-Matched Transplantation Wed, 02 Dec 2015 12:42:31 +0000 The implementation of high-dose posttransplantation cyclophosphamide (PTCy) has made HLA-haploidentical (haplo) blood or marrow transplantation (BMT) a cost effective and safe alternative donor transplantation technique, resulting in its increasing utilization over the last decade. We review the available retrospective comparisons of haplo BMT with PTCy and HLA-matched BMT in adults with hematologic malignancies. The examined studies demonstrate no difference between haplo BMT with PTCy and HLA-matched BMT with regard to acute graft-versus-host disease (aGVHD), nonrelapse mortality, and overall survival. Chronic GVHD occurred less frequently after haplo BMT with PTCy compared with HLA-matched BMT utilizing standard GVHD prophylaxis. In addition, patients with a high risk of relapse by the disease risk index had a suggestion of improved progression-free and overall survival after haplo BMT with PTCy when compared with a historical cohort of HLA-matched BMT in one analysis. Furthermore, in Hodgkin lymphoma relapse and progression-free survival were improved in the haplo BMT with PTCy compared with the HLA-matched BMT cohort. These findings support the use of this transplantation platform when HLA-matched related donors (MRDs) are unavailable and suggest that clinical scenarios exist in which haplo BMT may be preferred to HLA-matched BMT, which warrant further investigation. Shannon R. McCurdy and Ephraim J. Fuchs Copyright © 2015 Shannon R. McCurdy and Ephraim J. Fuchs. All rights reserved. Real-World Assessment of Clinical Outcomes in Patients with Lower-Risk Myelofibrosis Receiving Treatment with Ruxolitinib Mon, 09 Nov 2015 09:23:34 +0000 Few trial-based assessments of ruxolitinib in patients with lower-risk myelofibrosis (MF) have been conducted, and no studies have made such assessments in a real-world population. We assessed changes in spleen size and constitutional symptoms during ruxolitinib treatment using a retrospective, observational review of anonymized US medical record data of patients diagnosed with IPSS low-risk () or intermediate-1-risk () MF. The majority of patients were male (low risk, 60%; intermediate-1 risk, 69%). Most patients (92% and 77%) were still receiving ruxolitinib at the medical record abstraction date (median observation/exposure time, 8 months). The proportion of patients with moderate or severe palpable splenomegaly (≥10 cm) decreased from diagnosis (56%) to best response (12%). Fatigue was reported in 47% of patients and was the most common constitutional symptom. For most symptoms in both risk groups, shifts in the distribution of severity from more to less severe from diagnosis to best response were observed. Both patients with low-risk and intermediate-1-risk MF experienced a substantial decrease in spleen size with ruxolitinib treatment in real-world settings. For most symptoms examined, there were distinct improvements in the distribution of severity during ruxolitinib treatment. These findings suggest that patients with lower-risk MF may benefit clinically from ruxolitinib treatment. Keith L. Davis, Isabelle Côté, James A. Kaye, Estella Mendelson, Haitao Gao, and Julian Perez Ronco Copyright © 2015 Keith L. Davis et al. All rights reserved. Decitabine Compared with Low-Dose Cytarabine for the Treatment of Older Patients with Newly Diagnosed Acute Myeloid Leukemia: A Pilot Study of Safety, Efficacy, and Cost-Effectiveness Wed, 04 Nov 2015 06:00:25 +0000 Introduction. The incidence of Acute Myeloid Leukemia (AML) increases progressively with age and its treatment is challenging. This prospective case control study was undertaken to compare the safety, efficacy, and cost-effectiveness of decitabine with those of cytarabine in older patients with newly diagnosed AML who are not fit for intensive chemotherapy. Materials and Methods. 30 eligible patients above 60 years old with newly diagnosed AML were assigned to receive decitabine or cytarabine. The primary end point was overall survival (OS). The secondary objective was to compare adverse events and cost-effectiveness of therapy in the two study groups. Results. In this study, 15 patients received decitabine and 15 patients received cytarabine. The median OS was 5.5 months for each of the treatment groups. The hazard ratio between the treatment groups was 0.811 with 95% CI of 0.390 to 1.687. Toxicity profile was similar in both groups. Cost per cycle of chemotherapy in INR was 24,200 for decitabine and 1,600 for low-dose cytarabine group. Median of simplified cost-effectiveness ratio was 0.00022 for decitabine group and 0.0034 for low-dose cytarabine group. Conclusions. For elderly patients with AML, decitabine and low-dose cytarabine should be chosen based on the patient’s choice and affordability. Our study has shown that both of these agents have similar OS and toxicity. Low-dose cytarabine scores over decitabine in developing countries as it is more cost-effective. Linu A. Jacob, S. Aparna, K. C. Lakshmaiah, D. Lokanatha, Govind Babu, Suresh Babu, and Sandhya Appachu Copyright © 2015 Linu A. Jacob et al. All rights reserved. Profiling β Thalassemia Mutations in Consanguinity and Nonconsanguinity for Prenatal Screening and Awareness Programme Wed, 21 Oct 2015 07:15:33 +0000 Mutation spectrum varies significantly in different parts and different ethnic groups of India. Social factors such as preference to marry within the community and among 1st degree relatives (consanguinity) play an important role in impeding the gene pool of the disease within the community and so in society by and large. The present paper discusses the role of consanguinity in profiling of beta thalassemia mutation, and thus the approach for prenatal screening and prevention based awareness programme. Clinically diagnosed 516 cases of beta thalassemia were screened at molecular level. A detailed clinical Proforma was recorded with the information of origin of the family, ethnicity, and consanguinity. The present study reports that subjects originating from Uttar Pradesh, Uttarakhand, Bihar, and Jharkhand have c.92+5G>C and c.124_127delTTCT mutation as the commonest mutation compared to the subjects hailing from Madhya Pradesh and Chhattisgarh and Nepal where sickle mutation was found more common. In 40 consanguineous unions more common and specific beta mutations with higher rate of homozygosity have been reported. This consanguinity-based data helps not only in deciding target oriented prenatal diagnostic strategies but also in objective based awareness programmes in prevention of thalassemia major birth. Ravindra Kumar, Vandana Arya, and Sarita Agarwal Copyright © 2015 Ravindra Kumar et al. All rights reserved. The Iron Status of Sickle Cell Anaemia Patients in Ilorin, North Central Nigeria Thu, 15 Oct 2015 08:15:12 +0000 Objectives. Sickle cell anaemia (SCA) is one of the commonest genetic disorders in the world. It is characterized by anaemia, periodic attacks of thrombotic pain, and chronic systemic organ damage. Recent studies have suggested that individuals with SCA especially from developing countries are more likely to be iron deficient rather than have iron overload. The study aims to determine the iron status of SCA patients in Ilorin, Nigeria. Methods. A cross-sectional study of 45 SCA patients in steady state and 45 non-SCA controls was undertaken. FBC, blood film, sFC, sTfR, and sTfR/log sFC index were done on all subjects. Results. The mean patients’ serum ferritin (589.33 ± 427.61 ng/mL) was significantly higher than the mean serum ferritin of the controls (184.53 ± 119.74 ng/mL). The mean serum transferrin receptor of the patients (4.24 ± 0.17 μg/mL) was higher than that of the controls (3.96 ± 0.17 μg/mL) (). The mean serum transferrin receptor (sTfR)/log serum ferritin index of the patients (1.65 ± 0.27 μg/mL) was significantly lower than that of the control (1.82 ± 0.18 μg/mL) (). Conclusion. Iron deficiency is uncommon in SCA patients and periodic monitoring of the haematological, biochemical, and clinical features for iron status in SCA patients is advised. Musa A. Sani, James O. Adewuyi, Abiola S. Babatunde, Hannah O. Olawumi, and Rasaki O. Shittu Copyright © 2015 Musa A. Sani et al. All rights reserved. Erythrocyte Catalase Activity in More Frequent Microcytic Hypochromic Anemia: Beta-Thalassemia Trait and Iron Deficiency Anemia Wed, 07 Oct 2015 14:22:23 +0000 Most common microcytic hypochromic anemias are iron deficiency anemia (IDA) and β-thalassemia trait (BTT), in which oxidative stress (OxS) has an essential role. Catalase causes detoxification of H2O2 in cells, and it is an indispensable antioxidant enzyme. The study was designed to measure erythrocyte catalase activity (ECAT) in patients with IDA (10) or BTT (21), to relate it with thalassemia mutation type (β0 or β+) and to compare it with normal subjects (67). Ninety-eight individuals were analyzed since September 2013 to June 2014 in Tucumán, Argentina. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA2, catalase, and iron status were performed. β-thalassemic mutations were determined by real-time PCR. Normal range for ECAT was 70,0–130,0 MU/L. ECAT was increased in 14% (3/21) of BTT subjects and decreased in 40% (4/10) of those with IDA. No significant difference () was shown between normal and BTT groups, while between IDA and normal groups the difference was proved to be significant (). In β0 and β+ groups, no significant difference () was observed. An altered ECAT was detected in IDA and BTT. These results will help to clarify how the catalase activity works in these anemia types. Sandra Stella Lazarte, María Eugenia Mónaco, Cecilia Laura Jimenez, Miryam Emilse Ledesma Achem, Magdalena María Terán, and Blanca Alicia Issé Copyright © 2015 Sandra Stella Lazarte et al. All rights reserved. Determinants of Overall and Progression-Free Survival of Nigerian Patients with Philadelphia-Positive Chronic Myeloid Leukemia Mon, 07 Sep 2015 09:51:58 +0000 Objective. The tyrosine kinase inhibitors have markedly changed the disease course for patients with Ph+ and/or BCR-ABL1+ chronic myeloid leukemia (CML). This study was embarked upon to assess the long-term effects of imatinib therapy on survival in adult Nigerian patients with CML. Methods. All adult patients on imatinib (400–600 mg) seen from July 2003 to December 2010 were assessed. Male/female distribution was 171/101, with a median age of 38 (range, 20–75) years. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier techniques. Results. Of all the 272 patients, 205 were in chronic phase, 54 in accelerated phase, and five in blastic phase, at commencement of imatinib. As at December 2010, 222 were alive. OS at 1 and 5 years was 94% and 63%, while PFS was 89% and 54%, respectively. Similarly, amongst the 205 patients in chronic phase, OS at 1 and 5 years was 97% and 68%, while PFS was 92% and 57%. Conclusion. Imatinib’s place as first-line therapy in the treatment of CML has further been reinforced in our patients, with improved survival and reduced morbidity, comparable with outcomes in other populations. Anthony A. Oyekunle, Rahman A. Bolarinwa, Adesola T. Oyelese, Lateef Salawu, and Muheez A. Durosinmi Copyright © 2015 Anthony A. Oyekunle et al. All rights reserved. Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia Patients: A Report from Eastern India Sun, 06 Sep 2015 11:11:56 +0000 Introduction. Red blood cell (RBC) alloimmunization and autoimmunization remain a major problem in transfusion dependent thalassemic patients. There is a paucity of data on the incidence of RBC alloimmunization and autoimmunization in thalassemic patients from eastern part of India, as pretransfusion antibody screening is not routinely performed. Aims. To assess the incidence of RBC alloimmunization and autoimmunization in transfusion dependent thalassemic patients in eastern India. Materials and Methods. Total 500 thalassemia cases were evaluated. The antibody screening and identification were performed with commercially available panel cells (Diapanel, Bio-rad, Switzerland) by column agglutination method. To detect autoantibodies, autocontrol and direct antiglobulin tests were carried out using polyspecific coombs (IgG + C3d) gel cards in all patients. Results. A total of 28 patients developed RBC alloimmunization (5.6%) and 5 patients had autoantibodies (1%). Alloantibody against c had the highest incidence (28.57%) followed by E (21.42%). Five out of 28 (17.85%) patients had developed antibodies against both c and E. Conclusion. Data from this study demonstrate that the RBC alloantibody and autoantibody development rates are significant in our region. Thus, pretransfusion antibody screening needs to be initiated in eastern India in order to ensure safe transfusion practice. Suvro Sankha Datta, Somnath Mukherjee, Biplabendu Talukder, Prasun Bhattacharya, and Krishnendu Mukherjee Copyright © 2015 Suvro Sankha Datta et al. All rights reserved. Predictors of Outcome and Severity in Adult Filipino Patients with Febrile Neutropenia Thu, 03 Sep 2015 13:33:46 +0000 Aim. The study aimed to describe the profile of Filipino febrile neutropenia patients and to determine parameters associated with severe outcomes. Methods. This is a retrospective study of Filipino febrile neutropenia patients admitted to the Philippine General Hospital. Patients were described in terms of clinical presentation and stratified according to the presence or absence of severe outcomes. Prognostic factors were then identified using regression analysis. Results. 115 febrile episodes in 102 patients were identified. Regression analysis yielded prolonged fever >7 days prior to admission (OR 2.43; 95% CI, 0.77–7.74), isolation of a pathogen on cultures (OR 2.69; 95% CI, 1.04–6.98), and nadir absolute neutrophil count (ANC) < 100 during admission (OR 1.96; 95% CI, 0.75–5.12) as significant predictors of poor outcome. Factors that significantly correlated with better outcome were granulocyte colony-stimulating factor (G-CSF) use (OR 0.31; 95% CI, 0.11–0.85) and completeness of antibiotic therapy (OR 0.26; 95% CI, 0.10–0.67). Conclusion. Prolonged fever >7 days prior to admission, positive pathogen on cultures, and nadir ANC < 100 during admission predicted severe outcomes, whereas G-CSF use and complete antibiotic therapy were associated with better outcomes. These prognostic variables might be useful in identifying patients that need more intensive treatment and monitoring. Marc Gregory Y. Yu, Ralph Elvi M. Villalobos, Ma. Jasmin Marinela C. Juan-Bartolome, and Regina P. Berba Copyright © 2015 Marc Gregory Y. Yu et al. All rights reserved. Sucrose-Formulated Recombinant Factor VIII Dosing Flexibility in Prophylaxis Regimens: Experience from Postmarketing Surveillance Studies Wed, 19 Aug 2015 11:12:50 +0000 Objectives. Prophylaxis regimens for severe hemophilia A allowing more flexible dosing while maintaining efficacy may improve adherence and decrease the cost of prophylaxis. Here, we compared the clinical effectiveness of once- or twice-weekly versus ≥3-times-weekly prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS) in a “real-world” practice setting. Methods. Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on physician-assigned treatment regimens of 1-2 prophylaxis injections/wk () or ≥3 prophylaxis injections/wk (). Descriptive statistics were determined for annualized bleeding rates (ABRs). Results. Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the 1-2 prophylaxis injections/wk group and 3.9 (1.5; 9.3) in the ≥3 prophylaxis injections/wk group. Median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower with 1-2 prophylaxis injections/wk. As an estimate of prophylaxis success, 63% (≥3 prophylaxis injections/wk) to 84% of patients (1-2 prophylaxis injections/wk) had ≤4 annualized joint bleeds. Conclusions. Dosing flexibility and successful prophylaxis with rFVIII-FS were demonstrated. Very good bleeding control was achieved with both once-twice-weekly and ≥3-times-weekly prophylaxis dosing regimens. Thomas J. Humphries, Stephan Rauchensteiner, Claudia Tückmantel, Alexander Pieper, Monika Maas Enriquez, and Prasad Mathew Copyright © 2015 Thomas J. Humphries et al. All rights reserved. Corrigendum to “Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage” Wed, 19 Aug 2015 09:55:32 +0000 Arunima Ghosh, Andy Vo, Beverly K. Twiss, Colin A. Kretz, Mary A. Jozwiak, Robert R. Montgomery, and Jordan A. Shavit Copyright © 2015 Arunima Ghosh et al. All rights reserved. Plasmablastic Lymphoma: A Review of Current Knowledge and Future Directions Tue, 18 Aug 2015 11:20:56 +0000 Plasmablastic lymphoma (PBL) is an aggressive subtype of non-Hodgkin’s lymphoma (NHL), which frequently arises in the oral cavity of human immunodeficiency virus (HIV) infected patients. PBL shows diffuse proliferation of large neoplastic cells resembling B-immunoblasts/plasmablasts, or with plasmacytic features and an immunophenotype of plasma cells. PBL remains a diagnostic challenge due to its peculiar morphology and an immunohistochemical profile similar to plasma cell myeloma (PCM). PBL is also a therapeutic challenge with a clinical course characterized by a high rate of relapse and death. There is no standard chemotherapy protocol for treatment of PBL. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens have been the backbone while more intensive regimens such as cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine (CODOX-M/IVAC), or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) are possible options. Recently, a few studies have reported the potential value of the proteasome inhibitor bortezomib and thalidomide in PBL patients. The introduction of genes encoding artificial receptors called chimeric antigen receptors (CARs) and CAR-modified T cells targeted to the B cell-specific CD19 antigen have demonstrated promising results in multiple early clinical trials. The aim of this paper is to review the recent advances in epidemiology; pathophysiology; clinical, pathologic, and molecular characteristics; therapy; and outcome in patients with PBL. Ghaleb Elyamany, Eman Al Mussaed, and Ali Matar Alzahrani Copyright © 2015 Ghaleb Elyamany et al. All rights reserved. Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence Sun, 16 Aug 2015 08:17:17 +0000 Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed. Ali Zalpour and Thein Hlaing Oo Copyright © 2015 Ali Zalpour and Thein Hlaing Oo. All rights reserved. Prospects of Vitamin C as an Additive in Plasma of Stored Blood Sun, 09 Aug 2015 06:43:33 +0000 There is a dire necessity to improve blood storage and prolong shelf-life of blood. Very few studies have focused on oxidative stress (OS) in blood and its influence on plasma with storage. This study attempts to (i) elucidate the continuous changes occurring in plasma during storage through oxidant levels and antioxidant status and (ii) evaluate the influence of vitamin C (VC) as an additive during blood storage. Blood was drawn from male Wistar rats and stored for 25 days at 4°C. Blood samples were divided into control and experimental groups. Plasma was isolated every 5 days and the OS markers, antioxidant enzymes, lipid peroxidation, and protein oxidation products, were studied. Catalase activity increased in all groups with storage. Lipid peroxidation decreased in VC (10) but was maintained in VC (30) and VC (60). Although there were variations in all groups, carbonyls were maintained towards the end of storage. Advanced oxidation protein products (AOPP) increased in VC (30) and were maintained in VC (10) and VC (60). Sulfhydryls were maintained in all groups. Vitamin C could not sufficiently attenuate OS and hence, this opens the possibilities for further studies on vitamin C in combination with other antioxidants, in storage solutions. R. Vani, R. Soumya, H. Carl, V. A. Chandni, K. Neha, B. Pankhuri, S. Trishna, and D. P. Vatsal Copyright © 2015 R. Vani et al. All rights reserved. Association of ABO Blood Group Phenotype and Allele Frequency with Chikungunya Fever Tue, 21 Apr 2015 14:30:13 +0000 Background. The objective of this study was to investigate the association of the ABO blood group phenotype and allele frequency with CHIK fever. Methods. A rural community survey in Southern Thailand was conducted in August and September 2010. A total of 506 villagers were enrolled. Cases were defined as individuals having anti-CHIK IgG by hemagglutination ≥1 : 10. Results. There were 314 cases (62.1%) with CHIK seropositivity. Females were less likely to have positive anti-CHIK IgG with odds ratio (OR) (95% CI) of 0.63 (0.43, 0.93). All samples tested were Rh positive. Distribution of CHIK seropositivity versus seronegativity (P value) in A, B, AB, and O blood groups was 80 versus 46 (0.003), 80 versus 48 (0.005), 24 versus 20 (0.55), and 130 versus 78 (<0.001), respectively. However, chi-square test between ABO and CHIK infection showed no statistical significance . Comparison of the ABO blood group allele frequency between CHIK seropositivity and seronegativity was not statistically significant. Conclusion. This finding demonstrated no association of the ABO blood group phenotypes and allele frequencies with CHIK infection. Pairaya Rujirojindakul, Virasakdi Chongsuvivatwong, and Pornprot Limprasert Copyright © 2015 Pairaya Rujirojindakul et al. All rights reserved. Impaired Fibrinolysis in Angiographically Documented Coronary Artery Disease Mon, 23 Feb 2015 12:03:43 +0000 Impaired fibrinolysis may predispose to coronary artery disease (CAD). Hypofibrinolysis due to high levels of plasminogen activator inhibitor-1 (PAI-1) has been reported in CAD. A novel regulator of fibrinolytic activity, thrombin activatable fibrinolysis inhibitor (TAFI), has attracted attention in recent years. It acts by blocking the formation of a ternary complex of plasminogen, fibrin, and tissue plasminogen activator (t-PA). Previously ambiguous results regarding TAFI levels have been reported in CAD. We measured plasma levels of PAI-1 and TAFI antigen in 123 patients with age ranging from 40 to 65 years who had been submitted to coronary angiography and assessed the association of these markers with the extent of stenosis in three groups: angiographically normal artery (NAn), mild to moderate atheromatosis (MA), and severe atheromatosis (SA). Plasma levels of PAI-1 were increased in patients with severe atheromatosis compared to mild/moderate atheromatosis or to normal patients (66.60, 40.50, and 34.90 ng/mL, resp.; P < 0.001). For TAFI no difference was found between different groups. When patients were grouped in only two groups based on clinical cut-off point for intervention (stenosis less than or above 70%) we found increased plasma levels for PAI-1 (37.55 and 66.60 ng/mL, resp.; P < 0.001) and decreased plasma levels for TAFI (5.20 and 4.53 μg/mL, resp.; P = 0.04) in patients with stenosis above 70%. No difference was found in PAI-1 or TAFI levels comparing the number of affected vessels. Conclusion. As evidenced by a raised level of PAI-1 antigen, one can suggest an impaired fibrinolysis in stable CAD, although no correlation with the number of affected vessels was found. Curiously, a decreased plasma level of total TAFI levels was observed in patients with stenosis above 70%. Further studies measuring functional TAFI are required in order to elucidate its association with the extent of degree of atheromatosis. Adriano Basques Fernandes, Luciana Moreira Lima, Marinez Oliveira Sousa, Vicente de Paulo Coelho Toledo, Rashid Saeed Kazmi, Bashir Abdulgader Lwaleed, and Maria das Graças Carvalho Copyright © 2015 Adriano Basques Fernandes et al. All rights reserved. RhD Specific Antibodies Are Not Detectable in HLA-DRB1 Mice Challenged with Human RhD Positive Erythrocytes Wed, 31 Dec 2014 11:57:31 +0000 The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB1 to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD+ RBCs to mice transgenic for the human HLA DRB1 as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW), CD1(ICR), and NSA(CF-1). DRB1 mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB1 mice immunized with RhD+ erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB1 mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB1 transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed. Lidice Bernardo, Gregory A. Denomme, Kunjlata Shah, and Alan H. Lazarus Copyright © 2014 Lidice Bernardo et al. All rights reserved. H. pylori May Not Be Associated with Iron Deficiency Anemia in Patients with Normal Gastrointestinal Tract Endoscopy Results Wed, 31 Dec 2014 00:10:37 +0000 Background. The aim of this study was to investigate the association between iron deficiency anemia and H. pylori in patients with normal gastrointestinal tract endoscopy results. Materials and Methods. A total of 117 male patients with normal gastrointestinal tract endoscopy results were included in this retrospective study. The study and control groups included 69 and 48 patients with and without iron deficiency anemia, respectively. The prevalence of H. pylori, the number of RBCs, and the levels of HGB, HTC, MCV, iron, and ferritin were calculated and compared. Results. There was no statistically significant difference found between the groups according to the prevalence of H. pylori (65.2% versus 64.6%, ). Additionally, the levels of RBCs, HGB, HTC, MCV, iron, and ferritin in the patients in the study group were lower than those in the control group (). Finally, there was no association between iron deficiency anemia and H. pylori (OR 1.02, Cl 95% 0.47–2.22, and ). Conclusion. H. pylori is not associated with iron deficiency anemia in male patients with normal gastrointestinal tract endoscopy results. Tayyibe Saler, Şakir Özgür Keşkek, Sibel Kırk, Süleyman Ahbab, and Gülay Ortoğlu Copyright © 2014 Tayyibe Saler et al. All rights reserved. Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction Sun, 14 Dec 2014 12:34:27 +0000 Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder, diagnosed primarily in adult female smokers and characterized by an expansion of CD19+CD27+IgM+ memory B cells, by the presence of binucleated lymphocytes, and by a moderate elevation of serum IgM. The clinical course is usually benign, but it is not known whether or not PPBL might be part of a process leading to the emergence of a malignant proliferative disorder. In this study we sought to investigate the functional response of B cells from patients with PPBL by use of an optimal memory B cell culture model based on the CD40-CD154 interaction. We found that the proliferation of PPBL B cells was almost as important as that of B cells from normal controls, resulting in high immunoglobulin secretion with in vitro isotypic switching. We conclude that the CD40-CD154 activation pathway is functional in the memory B cell population of PPBL patients, suggesting that the disorder may be due to either a dysfunction of other cells in the microenvironment or a possible defect in another B cell activation pathway. Emmanuelle Dugas-Bourdages, Sonia Néron, Annie Roy, André Darveau, and Robert Delage Copyright © 2014 Emmanuelle Dugas-Bourdages et al. All rights reserved. Aromatic Amines Exert Contrasting Effects on the Anticoagulant Effect of Acetaldehyde upon APTT Mon, 08 Dec 2014 00:10:09 +0000 The pharmacological effects of amphetamine, procaine, procainamide, DOPA, isoproterenol, and atenolol upon activated partial thromboplastin time in the absence and presence of acetaldehyde have been investigated. In the absence of acetaldehyde, amphetamine and isoproterenol exhibit a procoagulant effect upon activated partial thromboplastin time, whereas atenolol and procaine display anticoagulant effects upon activated partial thromboplastin time. DOPA and procainamide do not alter activated partial thromboplastin time. Premixtures of procaine with acetaldehyde produce an additive anticoagulant effect on activated partial thromboplastin time, suggesting independent action of these compounds upon clotting factors. Premixtures of amphetamine with acetaldehyde, as well as atenolol with acetaldehyde, generate a detoxication of the anticoagulant effect of acetaldehyde upon activated partial thromboplastin time. A similar statistically significant decrease in activated partial thromboplastin time is seen when procainamide is premixed with acetaldehyde for 20 minutes at room temperature. Premixtures of DOPA and isoproterenol with acetaldehyde do not affect an alteration in activated partial thromboplastin time relative to acetaldehyde alone. Hence, a selective interaction of atenolol, procaine, and amphetamine with acetaldehyde to produce detoxication of the acetaldehyde is suggested, undoubtedly due to the presence of amino, hydroxyl, or amide groups in these drugs. La'Teese Hall, Sarah J. Murrey, and Arthur S. Brecher Copyright © 2014 La'Teese Hall et al. All rights reserved. Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update Thu, 27 Nov 2014 07:32:43 +0000 Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis. Paola Villafuerte-Gutierrez, Lucia Villalon, Juan E. Losa, and Cesar Henriquez-Camacho Copyright © 2014 Paola Villafuerte-Gutierrez et al. All rights reserved. Post-Autologous (ASCT) Stem Cell Transplant Therapy in Multiple Myeloma Mon, 24 Nov 2014 07:27:51 +0000 Autologous stem cell transplant (ASCT) is the standard of care in transplant-eligible multiple myeloma patients and is associated with significant improvement in progression-free survival (PFS), complete remission rates (CR), and overall survival (OS). However, majority of patients eventually relapse, with a median PFS of around 36 months. Relapses are harder to treat and prognosis declines with each relapse. Achieving and maintaining “best response” to initial therapy is the ultimate goal of first-line treatment and sustained CR is a powerful surrogate for extended survival especially in high-risk multiple myeloma. ASCT is often followed by consolidation/maintenance phase to deepen and/or maintain the response achieved by induction and ASCT. Novel agents like thalidomide, lenalidomide, and bortezomib have been used as single agents or in combination. Thalidomide use has been associated with a meaningful improvement in PFS and EFS, however, with substantial side effects. Data with lenalidomide maintenance after-ASCT is favorable, but the optimal duration of lenalidomide maintenance is still unclear. Bortezomib use has been associated with superior outcomes, predominantly in high-risk myeloma patients. Combination regimens utilizing a proteasome inhibitor (i.e., bortezomib) with an immunomodulatory drug (thalidomide or lenalidomide) have provided the best outcomes. This review article serves as a review of the best available evidence in post-ASCT approaches in multiple myeloma. Zeina Al-Mansour and Muthalagu Ramanathan Copyright © 2014 Zeina Al-Mansour and Muthalagu Ramanathan. All rights reserved. Outcome of Adolescents with Acute Lymphoblastic Leukemia Treated by Pediatrics versus Adults Protocols Mon, 17 Nov 2014 12:01:16 +0000 Objective. Several studies showed better outcome in adolescents and young adults with acute lymphoblastic leukemia (ALL) treated with pediatrics protocols than similarly aged patients treated with adults protocols, while other studies showed similar outcome of both protocols. We conducted this study to compare the outcome of our pediatrics and adults therapeutic protocols in treatment of adolescents ALL. Patients and Methods. We retrospectively reviewed files of 86 consecutive adolescent ALL patients aged 15–18 years who attended to outpatients clinic from January 2003 to January 2010. 32 out of 86 were treated with pediatrics adopted BFM 90 high risk protocol while 54 were treated with adults adopted BFM protocol. We analyzed the effect of different treatment protocols on achieving complete remission (CR), disease-free survival (DFS), and overall survival (OS). Results. The 2 patients groups have almost similar characteristics. The CR was significantly higher in pediatrics protocol 96% versus 89% . Despite the fact that the toxicity profiles were higher in pediatrics protocol, they were tolerable. Moreover, the pediatrics protocol resulted in superior outcome in EFS 67% versus 39% (), DFS 65% versus 41% , and OS 67% versus 45% . Conclusion. Our study’s findings recommend using intensified pediatrics inspired protocol to treat adolescents with acute lymphoblastic leukemia. Abeer Ibrahim, Amany Ali, and Mahmoud M. Mohammed Copyright © 2014 Abeer Ibrahim et al. All rights reserved. Evaluation of Prothrombin Time and Activated Partial Thromboplastin Time in Hypertensive Patients Attending a Tertiary Hospital in Calabar, Nigeria Sun, 16 Nov 2014 06:20:03 +0000 Introduction. Several biomedical findings have established the effects of hypertension on haemostasis and roles of blood coagulation products in the clinical course of hypertension. Methods. This cross-sectional study aimed at determining effects of hypertension on prothrombin time (PT) and activated partial thromboplastin time (APTT) in hypertensive patients in comparison with normotensive subjects attending a tertiary hospital in Calabar. Forty-two (42) hypertensive patients and thirty-nine (39) normotensive control subjects were investigated for PT and APTT using Quick one-stage methods. Results. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) correlated positively with APTT (, ; ) in hypertensive patients. DBP, SBP, PT, and APTT were significantly higher in hypertensive patients when compared to normotensive subjects (). DBP correlated negatively with duration of illness (; ) in hypertensive patients and positively with age of normotensive subjects (; ). Conclusion. The results obtained indicated that measurements of PT and APTT may serve as indices for evaluating hemostatic abnormalities in hypertensive patients and guide for antihypertensive therapy. However, to have better understanding of hemostatic activities in hypertension, it is recommended to conduct D-dimer, platelet factors, and protein assays. Nnamani Nnenna Adaeze, Anthony Uchenna Emeribe, Idris Abdullahi Nasiru, Adamu Babayo, and Emmanuel K. Uko Copyright © 2014 Nnamani Nnenna Adaeze et al. All rights reserved.