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ABSTRACT BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation for advanced indolent lymphoproliferative disorders remains to be established. OBJECTIVE: This paper aims to describe the results of allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders. METHODS: This article reports on 29 adult patients submitted to allogeneic transplantations from 1997 to 2010. RESULTS: Most had follicular non-Hodgkin lymphoma (n = 14) or chronic lymphocytic leukemia (n = 12). The median age was 44 years (range: 24-53 years) and 65% of patients were male. Only 21% had had access to rituximab and 45% to fludarabine. All had advanced disease (stage IV) with partial response or stable disease. Most underwent myeloablative conditioning n = 17 - 59%). In this scenario, refractory disease was observed in seven (24%) patients, the 100-day mortality rate was 17% (n = 5) and relapse occurred in four patients (18%). The main cause of death throughout the follow up was refractory disease in six of the 12 patients who died. Moderate and severe chronic graft-versus-host disease was frequent; about 41% of 24 patients analyzed. The overall survival rates and disease free survival at 42 months were 56.7% and 45.4%, respectively. According to Kaplan-Meyer analysis, the median time from diagnosis to transplant predicted the overall survival; however age, gender and conditioning regimen did not predict the prognosis. It was impossible to reach other conclusions because of the small sample size in this study. CONCLUSIONS: The role of allogeneic transplantations should be re-evaluated in the era of targeted therapy.

Resumo em Inglês:

ABSTRACT BACKGROUND: Children with sickle cell disease may have their quality of life affected by oral alterations. However, there is still little data on oral health-related quality of life in these children. The aim of this study was to investigate the influence of sickle cell disease, socioeconomic characteristics, and oral conditions on oral health-related quality of life of children and teens. METHOD: One hundred and six children and teens with sickle cell disease were compared to a similar sample of 385 healthy peers. Data were collected through oral examinations, interviews to assess quality of life (Child Perceptions Questionnaire for children aged 8-10 and 11-14) and questionnaires containing questions on socioeconomic status. RESULTS: There were no statistically significant differences in the total scores of the Child Perceptions Questionnaires or domain scores comparing sickle cell disease patients to control subjects. When sub-scales were compared, oral symptoms and functional limitations had a greater negative impact on the quality of life of adolescents with sickle cell disease (p-value <0.001 and p-value <0.01, respectively) when compared to healthy controls. The only statistically significant determinants of negative impact on oral health-related quality of life in the overall sample was home overcrowding (more than two people/room) in the younger children's group, and dental malocclusion among teens. CONCLUSION: There was no significant difference in the negative impact on the oral health-related quality of life between the group with sickle cell disease and the control group. Of the oral alterations, there was a significant difference in the oral health-related quality of life between adolescents with sickle cell disease and controls only in relation to malocclusion. Among the socioeconomic characteristics, only overcrowding was significantly associated with a negative impact on oral health-related quality of life.

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ABSTRACT BACKGROUND: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance. Multiple myeloma differs from other hematologic malignancies due to a high fraction of low proliferating malignant plasma cells and the paucity of plasma cells in bone marrow aspiration samples, making cytogenetic analysis a challenge. An abnormal karyotype is found in only one-third of patients with multiple myeloma and interphase fluorescence in situ hybridization is the most useful test for studying the chromosomal abnormalities present in almost 90% of cases. However, it is necessary to study the genetic abnormalities in plasma cells after their identification or selection by morphology, immunophenotyping or sorting. Other challenges are the selection of the most informative FISH panel and determining cut-off levels for FISH probes. This study reports the validation of interphase fluorescence in situ hybridization using CD138 positive cells, according to proposed guidelines published by the European Myeloma Network (EMN) in 2012. METHOD: Bone marrow samples from patients with multiple myeloma were used to standardize a panel of five probes [1q amplification, 13q14 deletion, 17p deletion, t(4;14), and t(14;16)] in CD138+ cells purified by magnetic cell sorting. RESULTS: This test was validated with a low turnaround time and good reproducibility. Five of six samples showed genetic abnormalities. Monosomy/deletion 13 plus t(4;14) were found in two cases. CONCLUSION: This technique together with magnetic cell sorting is effective and can be used in the routine laboratory practice. In addition, magnetic cell sorting provides a pure plasma cell population that allows other molecular and genomic studies.

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ABSTRACT BACKGROUND: According to the 2008 World Health Organization classification, mature B-cell neoplasms are a heterogeneous group of diseases that include B-cell lymphomas and plasma cell disorders. These neoplasms can have very different clinical behaviors, from highly aggressive to indolent, and therefore require diverse treatment strategies. OBJECTIVE: The aim of this study was to assess the profile of 93 patients diagnosed with mature B-cell neoplasms monitored between 2011 and 2014. METHODS: A review of patients' charts was performed and laboratory results were obtained using the online system of the Universidade Federal de Santa Catarina. RESULTS: The study included 93 adult patients with mature B-cell neoplasms. The most frequent subtypes were multiple myeloma, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and Burkitt's lymphoma. The median age at diagnosis was 58 years with a male-to-female ratio of 1.3:1. There were statistical differences in terms of age at diagnosis, lactate dehydrogenase activity and Ki-67 expression among the subtypes of B-cell lymphoma. According to the prognostic indexes, the majority of multiple myeloma patients were categorized as high risk, while the majority of chronic lymphocytic leukemia patients were classified as low risk. CONCLUSIONS: This study demonstrates the profile of patients diagnosed with mature B-cell neoplasms in a south Brazilian university hospital. Of the B-cell lymphoma, Burkitt's lymphoma presented particular features regarding lactate dehydrogenase activity levels, Ki-67 expression, age at diagnosis, and human immunodeficiency virus infection.

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ABSTRACT BACKGROUND: Myeloproliferative neoplasms are Philadelphia chromosome-negative diseases characterized by hyperproliferation of mature myeloid cells, associated or not with the Janus kinase 2 tyrosine kinase mutation, JAK2V617F. As there is no curative therapy, researchers have been investigating new drugs to treat myeloproliferative neoplasms, including l-amino acid oxidase from Calloselasma rhodostoma snake venom (CR-LAAO), which is a toxin capable of eliciting apoptosis in several tumor cell lines. OBJECTIVE: To evaluate the effects of l-amino acid oxidase from C. rhodostoma snake venom in the apoptotic machinery of JAK2-mutated cell lines. METHODS: The HEL 92.1.7 and SET-2 cell lines were cultured with l-amino acid oxidase and catalase for 12 h at 37 °C in 5% carbon dioxide. The cell viability was assessed by the multi-table tournament method, the level of apoptosis was measured by flow cytometry, and the expression of cysteine-dependent aspartate-specific proteases and cleaved Poly(ADP-ribose) polymerase were analyzed by Western blotting. RESULTS: l-Amino acid oxidase from C. rhodostoma snake venom was cytotoxic to HEL 92.1.7 and SET-2 cells (50% inhibitory concentration = 0.15 µg/mL and 1.5 µg/mL, respectively) and induced apoptosis in a concentration-dependent manner. Cell treatment with catalase mitigated the l-amino acid oxidase toxicity, indicating that hydrogen peroxide is a key component of its cytotoxic effect.The activated caspases 3 and 8 expression and cleaved PARP in HEL 92.1.7 and SET-2 cells confirmed the apoptosis activation by CR-LAAO. CONCLUSIONS: l-Amino acid oxidase from C. rhodostoma snake venom is a potential antineoplastic agent against HEL 92.1.7 and SET-2 JAK2V617F-positive cells as it activates the extrinsic apoptosis pathway.

Resumo em Inglês:

ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate) on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

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ABSTRACT BACKGROUND: The rapid increase in the aged population has resulted in a growing number of cases of chronic diseases. This increase is an important demographic change that low- and middle-income countries have to face and poses a new challenge to health services. One of the first steps to formulate public policies is to understand the reality of each country's aging population. This study describes the prevalence of anemia, hypertension and diabetes and the overall health status in pre-elderly and elderly subjects enrolled in two primary health care clinics, Eldorado and Piraporinha, in the city of Diadema, São Paulo. METHOD: A cross-sectional study was conducted with 373 participants. Clinical data were collected from patient charts and the degree of disability and common mental disorders, as well as demographic data were obtained by interviews. RESULTS: The prevalence of anemia was approximately 11% and hypertension was 70% and 81% in Eldorado and Piraporinha, respectively. The frequency of diabetes was 52% in Eldorado and 30% in Piraporinha. The subjects of both health care clinics reported having difficulties in some of their daily physical and instrumental activities, with physical symptoms and emotional disorders. CONCLUSION: Anemia, hypertension and diabetes are prevalent in the studied population, and patients showed degrees of dependency and impaired health status.