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Revista Brasileira de Hematologia e Hemoterapia, Volume: 39, Issue: 3, Published: 2017
  • Understanding population-wide haplotype frequencies of human leukocyte antigen (HLA) alleles in linkage disequilibrium is important for hematopoietic stem cell transplantation☆ Scientific Comments

    Otegbeye, Folashade
  • Adjusting thresholds of serum ferritin for iron deficiency: a moving target☆ Scientific Comments

    Naoum, Flávio Augusto
  • Challenges in the diagnosis of iron deficiency anemia in aged people☆ Scientific Comments

    Moraes, Niele Silva de; Figueiredo, Maria Stella
  • New agents in relapsed/refractory Hodgkin's lymphoma☆ Scientific Comments

    Biasoli, Irene; Spector, Nelson
  • BCR-ABL1 level monitoring in chronic myeloid leukemia by real time polymerase chain reaction in Brazil - not so real☆ Scientific Comments

    Pagnano, Katia Borgia Barbosa
  • Scientific comment on: "Quantitative flow cytometric evaluation of CD200, CD123, CD43 and CD52 as a tool for the differential diagnosis of mature B-cell neoplasms"☆ Scientific Comments

    Ikoma, Maura Rosane Valerio
  • Do immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study Original Articles

    Galindo-Rodríguez, Gabriela; Jaime-Pérez, José C.; Salinas-Carmona, Mario C.; González-Díaz, Sandra N.; Castro-Corona, Ángeles; Cavazos-González, Raúl; Treviño-Villarreal, Humberto; Heredia-Salazar, Alberto C.; Gómez-Almaguer, David

    Abstract in English:

    Abstract Background l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. Methods Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. Results Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value = 0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2-4), compared to none of the nine children who relapsed who had positive skin tests (p-value < 0.001). Conclusion Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse.
  • Molecular response to imatinib mesylate of Brazilian patients with chronic myeloid leukemia Original Articles

    Vieira-Mion, Ana Lucia; Pereira, Noemi Farah; Funke, Vaneuza Araujo Moreira; Pasquini, Ricardo

    Abstract in English:

    Abstract Background Imatinib mesylate has revolutionized the treatment of chronic myeloid leukemia leading to significant reductions of BCR-ABL1 transcript levels in peripheral blood. Objective To evaluate the response to imatinib mesylate treatment (400 mg/day) in Brazilian patients in the chronic phase of chronic myeloid leukemia monitored by quantitative real time polymerase chain reaction. Methods Between October 2002 and October 2010, 3169 peripheral blood samples were collected from 1403 patients from 3 to 5 months, 6 to 11 months, 12 to 17 months, 18 to 23 months and ≥24 months after beginning imatinib treatment. Eighty-two patients had samples available and analyzed for all time intervals. BCR-ABL1 quantification was performed by quantitative real time polymerase chain reaction using the ABL1 gene as the control. Results of the BCR-ABL1 ratio as a percentage were reported by the international scale (IS) using the laboratory conversion factor (0.51). Results In the first interval, 80.8% of patients achieved the optimal response (BCR-ABL1IS ≤ 10%). In the second period, 69.1% achieved optimal response (BCR-ABL1IS ≤ 1%) and, between 12 and 17 months, 47.3% achieved major molecular response (BCR-ABL1IS ≤ 0.1%). Conclusions The results of this retrospective study show that the response to imatinib treatment (400 mg/day) of Brazilian patients in the chronic phase of chronic myeloid leukemia is within the expected profile when compared to patients reported in international prospective randomized studies.
  • Everolimus as a single agent in refractory or relapsed Hodgkin's lymphoma: the Brazilian Named Patient Program Experience Original Articles

    Rocha, Talita Máira Bueno da Silveira da; Fortier, Sergio Costa; Fischer, Thais Rodrigues da Cunha; Perini, Guilherme Fleury; Gaiolla, Rafael Dezen; Fogliatto, Laura; Delamain, Marcia Torresan; Costa, Andressa Fragoso da; Castro, Nelson Siqueira de; Barretos, Wolney Gois; Souza, Cármino Antonio de; Buccheri, Valéria; Chiattone, Carlos Sérgio

    Abstract in English:

    Abstract Background Despite all the scientific progress that has been made on understanding the disease, prognosis for patients with relapsed and refractory Hodgkin's lymphoma remains poor and the treatment is palliative in the majority of the cases. Thus, the aim of this study was to present the results on the compassionate use of everolimus in a group of patients who were monitored at nine different centers in Brazil. Methods A 10-mg oral dose of everolimus was given to each patient daily. Response time was evaluated from the beginning of medication use until loss of response, toxicity or medical decision to cease treatment. Results Thirty-three patients were evaluated. The median age at the beginning of medication administration was 29 years. Patients had received a median of five prior therapies. Overall response rate was 45.4%, with 13 patients achieving partial response, two achieved clinical response, 14 remained with stable disease, two had disease progression, and two were not evaluated. Patients received a median of 14 cycles. Progression-free survival was nine months, and overall survival was estimated to be 36 months. Three patients used the medication for more than four years. The most frequently reported adverse events were thrombocytopenia and hypercholesterolemia. Three patients had pulmonary toxicity. Grade III and IV adverse events occurred in 39% of the patients. Conclusion Everolimus was found to provide a response in a group of patients with refractory or relapsed Hodgkin's lymphoma who had adequate tolerability to the drug.
  • Ability of serum ferritin to diagnose iron deficiency anemia in an elderly cohort Original Articles

    Babaei, Mansour; Shafiei, Sajedeh; Bijani, Ali; Heidari, Behzad; Hosseyni, Seyed Reza; Vakili Sadeghi, Mohsen

    Abstract in English:

    Abstract Background Diagnosis and treatment of iron deficiency anemia in older subjects improves their quality of life. Serum ferritin as a marker of iron stores is an acute phase protein. In older subjects who usually have many concomitant chronic medical conditions, serum ferritin may increase in response to inflammatory processes irrespective of iron stores. This study was performed to determine the diagnostic properties of serum ferritin in the diagnosis of iron deficiency anemia in older subjects. Methods This case-control study included all the inhabitants of Amirkola town who participated in the Amirkola Health and Aging Project. Diagnosis of anemia was confirmed based on a hemoglobin level <13 g/dL in men and <12 g/dL in women and iron deficiency anemia by percent transferrin saturation <15%. A receiver operating characteristic curve was constructed to determine an optimal serum ferritin cutoff value to differentiate patients with and without iron deficiency anemia at the highest sensitivity and specificity. Results Eighty patients with iron deficiency anemia and 160 cases of anemia without iron deficiency (mean age: 72.9 ± 8 and 71.6 ± 7.6 years, respectively; p-value = 0.37) were analyzed. In iron deficiency anemia, the mean serum ferritin was significantly lower (p-value = 0.036) compared to patients without iron deficiency anemia. Serum ferritin with a cutoff level of 100 ng/mL differentiated patients with and without iron deficiency anemia with a sensitivity of 60% and specificity of 59% and area under the receiver operating characteristic curve of 0.615 ± 0.040 (95% confidence interval: 0.536-0.694; p-value = 0.004). Conclusion These findings indicate that in elderly subjects, iron deficiency anemia may develop with higher levels of serum ferritin. Hence, the conventional cutoff of serum ferritin for the diagnosis of iron deficiency anemia in young adults is not appropriate for the elderly population.
  • Human leukocyte antigen allele linkage disequilibrium and haplotype structure in volunteer bone marrow donors of Paraná State Original Articles

    Costantino, Paulo Rincoski; Zeck, Suelen Camargo; Silva, Waldir Antonio da; Bicalho, Maria da Graça

    Abstract in English:

    Abstract Background Bone marrow transplantation has been used in the treatment of various diseases, especially hematologic diseases. The success of this treatment, among other factors, requires human leukocyte antigens (HLA) compatibility between patient and donor. Knowing the human leukocyte antigens allele group and haplotype frequencies as well as the linkage disequilibrium between alleles of different human leukocyte antigens loci can shorten the search time for a compatible bone marrow donor. Objective To assemble and analyze data on human leukocyte antigens frequencies available in the Laboratory of Immunogenetics and Histocompatibility (LIGH) database of the Universidade Federal do Paraná adding an estimation of the Hardy-Weinberg equilibrium and linkage disequilibrium. Methods The sample was composed of seven populations grouped by self-declared ancestry or inferred from the surname as follows: Laboratory of Immunogenetics and Histocompatibility database (all groups), descendants of Italians, Poles, and Asians, Afro-Brazilians, Mulattos (mixed ancestry) and Amerindians. Human leukocyte antigens genotyping was carried out using the polymerase chain reaction-sequence specific primers (PCR-SSP) and -sequence specific oligonucleotide (PCR-SSO) technologies. Results There were high frequencies of the HLA-A*02, HLA-B*35 and HLA-DRB1*13 allelic groups in all groups. The same was observed for the HLA-A*01-B*08-DRB1*03 haplotype except for Asian descendants. It was observed that the human leukocyte antigens Laboratory of Immunogenetics and Histocompatibility database and the Asian group are not in Hardy-Weinberg equilibrium. The Italian, Polish, Asian, Mulatto and Amerindian descendants showed haplotypes in complete linkage disequilibrium. Our results were compared with data on the human leukocyte antigens in the Paraná population available from the Brazilian Voluntary Bone Marrow Donor Registry (REDOME) and data published on the population of Curitiba and the northern region of Paraná. Conclusions Haplotypes frequent in the Asian group were not the most frequently observed in the Laboratory of Immunogenetics and Histocompatibility database and the National Bone Marrow Donor Registry for the state of Paraná. Linkage disequilibrium information may prove useful in the search for bone marrow donors for patients awaiting a suitable donor.
  • Comparison of microRNA expression in high-count monoclonal B-cell lymphocytosis and Binet A chronic lymphocytic leukemia Original Articles

    Furtado, Felipe Magalhães; Scheucher, Priscila Santos; Santana, Bárbara Amélia; Zanette, Dalila Lucíola; Calado, Rodrigo do Tocantins; Rego, Eduardo Magalhães; Matos, Daniel Mazza; Falcão, Roberto Passetto

    Abstract in English:

    Abstract Background Evidence suggests that monoclonal B-cell lymphocytosis precedes all chronic lymphocytic leukemia cases, although the molecular mechanisms responsible for disease progression are not understood. Aberrant miRNA expression may contribute to the pathogenesis of chronic lymphocytic leukemia. The objective of this study was to compare miRNA expression profiles of patients with Binet A chronic lymphocytic leukemia with those of subjects with high-count monoclonal B-cell lymphocytosis and healthy volunteers (controls). Methods Twenty-one chronic lymphocytic leukemia patients, 12 subjects with monoclonal B-cell lymphocytosis and ten healthy volunteers were enrolled in this study. Flow cytometry CD19+CD5+-based cell sorting was performed for the chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis groups and CD19+ cells were sorted to analyze the control group. The expressions of miRNAs (miR-15a, miR-16-1, miR-29b, miR-34a, miR-181a, miR-181b and miR-155) were determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results Significant differences between the expressions in the chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis groups were restricted to the expression of miR-155, which was higher in the former group. A comparison between healthy controls and monoclonal B-cell lymphocytosis/chronic lymphocytic leukemia patients revealed higher miR-155 and miR-34a levels and lower miR-15a, miR-16-1, miR-181a and miR-181b in the latter group. Conclusions Our results show a progressive increase of miR-155 expression from controls to monoclonal B-cell lymphocytosis to chronic lymphocytic leukemia. The role of miR-155 in the development of overt chronic lymphocytic leukemia in individuals with monoclonal B-cell lymphocytosis must be further analyzed.
  • Blood/Injection Fear Scale: Portuguese version, cultural adaptation and psychometric properties in a large sample of primary health care users Original Articles

    Zucoloto, Miriane Lucindo; Martinez, Edson Zangiacomi

    Abstract in English:

    Abstract Background Blood/injection phobia may have important consequences for health. These phobic individuals, in most cases, avoid contact with health systems, postpone or avoid medical procedures, avoid invasive treatments and do not participate in health promotion and early detection of disease initiatives such as vaccination, consultations, preventive exams or blood donation. Thus, specific and validated instruments are necessary to assess this variable. In addition, a lack of studies on this theme may be associated with the low availability of instruments. This study aimed to propose a Portuguese version of the Blood/Injection Fear Scale (BIFS-P) and assess its psychometric properties. Methods Translation and back-translation were performed. Content validity was assessed in two steps by a panel of 20 experts. The psychometric properties were assessed in a stratified and representative sample of primary health care service users of Ribeirão Preto, southeastern Brazil. Exploratory and confirmatory factor analyses were conducted using a polychoric correlation matrix. Results A total of 1054 primary health care users participated; 79.7% were female and the mean age was 40.6 (standard deviation = 15.16) years. According to the exploratory factor analysis, the items can be grouped into three or five factors with best fits being detected for the three- and five-factor models in confirmatory factor analysis. Conclusion Blood/Injection Fear Scale (Portuguese version) is easy to understand and apply in the general population, showed adequate psychometric properties, and represents an alternative in the assessment of blood/injection phobia for future studies.
  • Quantitative flow cytometric evaluation of CD200, CD123, CD43 and CD52 as a tool for the differential diagnosis of mature B-cell neoplasms Original Articles

    Arlindo, Elissandra Machado; Marcondes, Natália Aydos; Fernandes, Flavo Beno; Faulhaber, Gustavo Adolpho Moreira

    Abstract in English:

    Abstract Background Distinction between mature B-cell neoplasms can be difficult due to overlapping of immunologic features and clinical manifestations. This study investigated whether quantifying mean fluorescence intensity of four monoclonal antibodies in a flow cytometry panel is useful for the differential diagnosis and characterization of these disorders. Methods The expressions of CD52, CD200, CD123 and CD43 were analyzed in samples from 124 patients with mature B-cell neoplasms. The quantitative estimation of these antigens was assessed by mean fluorescence intensity. Results The cases included were 78 chronic lymphocytic leukemias, three atypical chronic lymphocytic leukemias, six marginal zone lymphomas, 11 splenic marginal zone lymphomas, nine lymphoplasmacytic lymphomas, six mantle cell lymphomas, two hairy cell leukemias, two hairy cell leukemias variant, five follicular lymphomas, one Burkitt lymphoma and one diffuse large B-cell lymphoma. The mean fluorescence intensity of CD200 was higher in atypical chronic lymphocytic leukemia, chronic lymphocytic leukemia and hairy cell leukemia cases. CD123 showed higher mean fluorescence intensities in hairy cell leukemia cells. Chronic lymphocytic leukemia, atypical chronic lymphocytic leukemia and mantle cell lymphoma had higher expression of CD43 and all follicular lymphoma cases had very low mean fluorescence intensity values. CD52 expression was consistently positive among all cases. Conclusion Quantitative evaluation of these markers can be a useful additional tool to better identify some types of mature B-cell neoplasms.
  • Thrombin generation assays for global evaluation of the hemostatic system: perspectives and limitations Review Articles

    Duarte, Rita Carolina Figueiredo; Ferreira, Cláudia Natália; Rios, Danyelle Romana Alves; Reis, Helton José dos; Carvalho, Maria das Graças

    Abstract in English:

    Abstract The existing techniques to evaluate hemostasis in clinical laboratories are not sensitive enough to detect hypercoagulable and mild hypocoagulable states. Under different experimental conditions, the thrombin generation test may meet these requirements. This technique evaluates the overall balance between procoagulant and anticoagulant forces and has provided new insights in our understanding of the coagulation cascade, as well as of the diagnosis of hypocoagulability and hypercoagulability conditions. Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. The calibrated automated thrombogram method is an open system, in which different antibodies, proteins, enzymes and peptides can be introduced to answer specific questions regarding hemostatic processes. The thrombin generation test has great clinical potential, such as in monitoring patients taking anticoagulants and antiplatelet drugs, screening for genetic or acquired thrombotic disorders, and evaluating bleeding risk control in patients with hemophilia using bypass agents or replacement therapy. Different to conventional coagulation tests, the thrombin generation test can be used for an overall evaluation of hemostasis, the results of which can then be used to evaluate specific characteristics of hemostasis, such as prothrombin time, activated partial thromboplastin time, and levels of fibrinogen and other coagulation factors. The introduction of this method will contribute to a better understanding and evaluation of overall hemostatic processes; however, this method still requires standardization and clinical validation.
  • Partnership of the Sociedade Brasileira de Oncologia Pediátrica and International Society of Pediatric Oncology to improve nutritional care for children with cancer in Brazil Review Articles

    Viani, Karina; Odone, Vicente; Ferman, Sima; Fonseca, Teresa Cristina Cardoso; Oliveira, Vanessa da Cunha; Lemos, Priscila dos Santos Maia; Barr, Ronald D.; Ladas, Elena J.

    Abstract in English:

    Abstract The authors present a proposal of a partnership between the Sociedade Brasileira de Oncologia Pediátrica (SOBOPE) and the International Society of Pediatric Oncology (SIOP) to promote the standardization and improvement of nutritional care of kids under cancer treatment in Brazil. The results of the first meeting in Brazil as well as plans for future meetings are described.
  • Small cell variant of anaplastic large cell lymphoma with leukemic presentation: a diagnostic challenge Case Reports

    Zecchini Barrese, Tomás; Sagramoso, Carlo; Bacci, Francesco; Sabattini, Elena
  • Flow cytometry to identify bone-marrow relapse in blastic plasmacytoid dendritic cell neoplasm: a case report Case Reports

    Farias, Mariela Granero; Pedrazzani, Fabiane Spagnol; Contin, Luis Carlos Zanandrea; Alegretti, Ana Paula; Rigoni, Lisandra Della Costa; Daudt, Liane Esteves
  • Erythrovirus B19 induced persistent bicytopenia in a healthy child Case Reports

    Jain, Mili; Oberoi, Gurleen; Kumar, Rashmi; Kumar, Ashutosh
  • Is karyotyping still needed in the diagnosis and monitoring of chronic myeloid leukemia? Letters To The Editor

    Chauffaille, Maria de Lourdes L.F.
  • FMS-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD): a villain among others Letter To The Editor

    Arruda, Vanessa Y.N. de; Matsuzaki, Lisa N.; Chauffaille, Maria de Lourdes
  • Patients with very severe anemia: a case series Letter To The Editor

    Cei, Marco; Ferretti, Alessandro; Mumoli, Nicola
  • Assessment of the Matos & Carvalho index for distinguishing thalassemia from iron deficiency anemia Letter To The Editor

    Hoffmann, Johannes J.M.L.; Urrechaga, Eloísa
  • Response to the assessment of the Matos & Carvalho index by Hoffmann and Urrechaga Letter To The Editor

    Matos, Januária F.; Dusse, Luci M.S.; Borges, Karina B.G.; Castro, Ricardo L.V. de; Coura-Vital, Wendel; Carvalho, Maria das G.
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