Prognostic Factors, Survival Analyses and the Risk of Second Primary Cancer: A Population-Based Study on Burkitt Lymphoma/Leukemia.

Burkitt lymphoma/leukemia (BL/L) is an aggressive oncohematological disease. This study evaluated the population-based prognosis and survival on BL/L as well as if BL/L behaved as a risk factor for the development of second primary cancers (SPCs) and if other first tumors behaved as risk factors for the occurrence of BL/L as an SPC. A retrospective cohort using the Surveillance, Epidemiology and End Results (SEER) Program (2008-2016) was performed. Kaplan-Meier, time-dependent covariate Cox regression and Poisson regression models were conducted. Overall, 3094 patients were included (median, 45 years; IQR, 22-62). The estimated overall survival was 65.4 months (95% CI, 63.6-67.3). Significantly more deaths occurred for older patients, black race, disease at an advanced stage, patients without chemotherapy/surgery and patients who underwent radiotherapy. Hodgkin lymphomas (nodal) (RR, 7.6 (3.9-15.0; p < 0.001)), Kaposi sarcomas (34.0 (16.8-68.9; p < 0.001)), liver tumors (3.4 (1.2-9.3; p = 0.020)) and trachea, mediastinum and other respiratory cancers (15.8 (2.2-113.9; p = 0.006)) behaved as risk factors for the occurrence of BL/L as an SPC. BL/L was a risk factor for the occurrence of SPCs as acute myeloid leukemias (4.6 (2.1-10.4; p < 0.001)), Hodgkin lymphomas (extranodal) (74.3 (10.0-549.8; p < 0.001)) and Kaposi sarcomas (35.1 (12.1-101.4; p < 0.001)). These results may assist the development of diagnostic and clinical recommendations for BL/L.

Chemotherapy Treatments for Burkitt Lymphoma: Systematic Review of Interventional Studies.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive hematologic cancer. This study synthetized the evidence about the efficacy and safety of chemotherapy treatments used in patients with BL using the World Health Organization classification. MATERIALS AND METHODS: A systematic review of interventional studies was performed. A search was carried out in PubMed, Scopus, and Web of Science, with additional manual and gray literature searches. The methodological quality of articles was assessed with the Newcastle-Ottawa scale. RESULTS: We identified 1358 studies; 9 nonrandomized studies satisfied the eligibility criteria (n = 544 patients). The BL epidemiologic variants were sporadic BL (44.5%), endemic BL (47.2%), and immunodeficiency-associated BL (8.3%). Regarding chemotherapy protocols, 4 groups were identified: based on CODOX-M/IVAC (n = 4), EPOCH (n = 1), BFM (n = 1), and simplified treatment schemes used in African countries (n = 3). Most studies had moderate quality. Empirically and qualitatively, the best options for adults with sporadic BL were 'DA-EPOCH-R' (7-year overall survival [OS], 100%; 95% confidence interval [CI], 82-100), 'HDR + LD into CODOX-M/IVAC' (2-year OS, 84%), and 'RD-CODOX-M/IVAC' (4-year progression-free survival, 92%; 95% CI, 77-100); in pediatric patients, the 'BFM-NHL-90-like' showed promising results (3-year OS, 90%). For immunodeficiency-associated BL, the 'SC-EPOCH-RR' demonstrated a good therapeutic profile (6-year OS, 90%; 95% CI, 60-98). The 'Malawi 2012-2014' (1-year OS, 73%; 95% CI, 61-85) could be the treatment choice in endemic BL (African countries). The main adverse events were hematologic. CONCLUSION: Selecting chemotherapy protocols for BL should be grounded in its epidemiologic variants. Further studies with greater methodological quality are needed to strengthen the evidence.

Follow-up and outcome of the twelve-year experience in adult patients with acute promyelocytic leukemia

ABSTRACT Acute promyelocytic leukemia is a subtype of acute myeloid leukemia, characterized by the presence of neoplastic promyelocytes, due to the reciprocal balanced translocation between chromosomes 15 and 17. Currently, with the use of agents that act directly on this molecular change, such as all-trans retinoic acid and arsenic trioxide, APL has shifted from a highly mortal to a curable disease. However, some cases are still at high risk of death, especially early death, and acquiring a better understanding of the clinical and biological factors involving APL is needed to correctly identify and treat such cases. The early suspected diagnosis and prompt initiation of the target therapy are important for better response rates. The follow-up and outcomes, using real-life data from 44 consecutive APL patients, were studied between 2001 and 2013. The overall survival rate was 82.7% and early death was 16%. Almost all patient deaths were due to severe bleeding, which was confirmed by multivariate analysis, as the most important prognostic factor leading to death. A better understanding the pathogenesis of the hemorrhagic complications in APL is needed, as well as the risk factors associated with early death in APL patients, as this has become synonymous with overall mortality.

An evolutionary recent IFN/IL-6/CEBP axis is linked to monocyte expansion and tuberculosis severity in humans.

Monocyte counts are increased during human tuberculosis (TB) but it has not been determined whether Mycobacterium tuberculosis (Mtb) directly regulates myeloid commitment. We demonstrated that exposure to Mtb directs primary human CD34+ cells to differentiate into monocytes/macrophages. In vitro myeloid conversion did not require type I or type II IFN signaling. In contrast, Mtb enhanced IL-6 responses by CD34+ cell cultures and IL-6R neutralization inhibited myeloid differentiation and decreased mycobacterial growth in vitro. Integrated systems biology analysis of transcriptomic, proteomic and genomic data of large data sets of healthy controls and TB patients established the existence of a myeloid IL-6/IL6R/CEBP gene module associated with disease severity. Furthermore, genetic and functional analysis revealed the IL6/IL6R/CEBP gene module has undergone recent evolutionary selection, including Neanderthal introgression and human pathogen adaptation, connected to systemic monocyte counts. These results suggest Mtb co-opts an evolutionary recent IFN-IL6-CEBP feed-forward loop, increasing myeloid differentiation linked to severe TB in humans.

The importance of CD39, CD43, CD81, and CD95 expression for differentiating B cell lymphoma by flow cytometry.

BACKGROUND: B cell lymphomas' (BCL) current diagnosis is usually based on a combination of morphology, immunophenotype, recurrent cytogenetic aberration and clinical features. However, even with these diagnostic tools, a definitive diagnosis can be difficult to achieve. Therefore, the aim of this study was to assess the profile of CD39, CD43, CD81, and CD95 expressions in diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and Burkitt lymphoma (BL) cases. METHODS: To address this issue, we investigated the expression of CD39, CD43, CD81, and CD95 by eight-color flow cytometry in retrospective cases from 2014 to 2016. RESULTS: The study included 27 adult patients diagnosed with DLBCL, FL, and BL during the study period. Four patients were diagnosed with germinal center B cell-like DLBCL (GCB DLBCL), seven with non-GCB DLBCL, nine with FL, and seven with BL. CD39 seems to be especially relevant to differentiate non-GCB DLBCL from BL and from FL. BL showed stronger expression of CD43 when compared to FL and GCB DLBCL. Moreover, CD43 may help to distinguish non-GCB DLBCL from GCB DLBCL. CD81 expression was much stronger in BL when compared to the other three groups of patients. Lastly, CD95 may also help to distinguish BL from the other subtypes, as BL cells expressed this antigen at low levels. CONCLUSIONS: In combination, CD39, CD43, CD81, and CD95 expressions appear to be helpful to distinguish CD10+ BCL, particularly BL. Phenotypic distinction between FL and GCB DLBCL remains challenging and requires further studies. © 2017 International Clinical Cytometry Society.

Câncer de pulmão: dados de três anos do registro hospitalar de câncer de um hospital do sul do Brasil / Lung cancer: three years of data hospital cancer registry of a Brazil south hospital

O Câncer de pulmão é uma neoplasia frequente. Na região sul, observam-se as maiores taxas de incidência e mortalidade relacionadas à doença no país. Objetivou-se avaliar o perfil dos pacientes com câncer de pulmão, atendidos no em um hospital do sul do Brasil. Como metodologia foi realizado um estudo retrospectivo, transversal, descritivo e analítico que utilizou o banco de dados do referido hospital, no período de 2007 a 2010. Analisou-se dados demográficos, socioeconômicos, características da neoplasia, diagnósticos e tratamentos.Foram avaliados dados de 103 pacientes com câncer de pulmão, com idade mediana de 65 anos, sexo masculino (71,8%), brancos (78,6%), com até primeiro grau incompleto (67%). O principal tipo histológico foi adenocarcinoma (24,3%). Não havia informação sobre o estadiamento em 48,5% dos pacientes. O estádio 4foi encontrado em 18,4% e apenas 10,7% apresentavam estadios precoces (I e II). A mediana dos dias entre primeira consulta e diagnóstico foi de 15 dias e entre o diagnóstico e o primeiro tratamento9dias. A principal forma de diagnóstico foi através de exame histológico do tumor primário (48,5%). Apenas 27,2% dos pacientes realizaram tratamento na própria instituição e 14,6% realizaram cirurgia de ressecção tumoral. A maioria (74,8%) não realizou nenhum tratamento no hospital. Observou-se uma tendência dos adenocarcinomasemse apresentarem em estadios precoces. Este hospital não realizou a maior parte do tratamento e nem o seguimento da maioria destes pacientes, mas desempenhou importante papel na investigação diagnóstica.

Lung cancer is a common cancer. In the southern region, are observed the highest incidence and mortality rates related to the disease in the country. The objective was to evaluate the profile of patients with lung cancer treated at a hospital in southern Brazil. The methodology was conducted a retrospective, cross-sectional, descriptive and analytical study using the Hospital database, from 2007 to 2010. We analyzed demographic, socioeconomic, tumor characteristics, diagnosis and treatment. Data were collected from 103 patients with lung cancer, with a median age of 65, male (71.8%), white (78.6%), with up to incomplete primary education (67%). The main histological type was adenocarcinoma (24.3%). There was no information about the staging in 48.5% of patients. The stadium 4foi found in 18.4% and only 10.7% had early stages (I and II). The median of days between the first visit and diagnosis was 15 days and between the first diagnosis and treatment 9dias. The main form of diagnosis was by histological examination of the primary tumor (48.5%). Only 27.2% of the patients underwent treatment at the institution and 14.6% underwent tumor resection. Most (74.8%) did not perform any treatment in the hospital. There was a tendency of adenocarcinomas in presenting themselves at early stages. This hospital did not perform most of the treatment nor the follow-up of most of these patients, but played an important role in diagnosis.

Mature B cell neoplasms: retrospective analysis of 93 cases diagnosed between 2011 and 2014 in a University Hospital in southern Brazil.

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.

Impact of leukemia and lymphoma chemotherapy on oral cavity and quality of life.

This study aimed to understand how patients perceive their oral health and the resulting oral manifestations of antineoplastic chemotherapy, as well as to analyze the impact of these alterations on oral health-related quality of life. A total of 80 patients undergoing treatment participated in this study. A questionnaire was applied using the Oral Health Impact Profile (OHIP-14) index and open interviews. Items with the highest impact prevalence included "worsened taste of food sensation" (35.00%), "discomfort in eating food" (20.00%), and "feeling stressed" (17.50%). The outpatients showed the highest prevalence scores, whereas the inpatients presented higher quality of life impact severity. The ways in which the patients perceived how their oral alteration affected their quality of life were distinct and subjective. It is important that dentists act together with a multiprofessional team developing strategies to alleviate the impact of the disease and chemotherapy on oral cavity and patients' quality of life.

Dental treatment in patients with leukemia.

Dental treatment of patients with leukemia should be planned on the basis of antineoplastic therapy which can be chemotherapy with or without radiotherapy and bone marrow transplantation. Many are the oral manifestations presented by these patients, arising from leukemia and/or treatment. In addition, performing dental procedures at different stages of treatment (before, during, or after) must follow certain protocols in relation to the haematological indices of patients, aimed at maintaining health and contributing to the effectiveness of the results of antineoplastic therapy. Through a literature review, the purpose of this study was to report the hematological abnormalities present in patients with leukemia, trying to correlate them with the feasibility of dental treatment at different stages of the disease. It is concluded in this paper that dental treatment in relation to haematological indices presented by patients with leukemia must follow certain protocols, mainly related to neutrophil and platelet counts, and the presence of the dentist in a multidisciplinary team is required for the health care of this patient.

Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

Evaluation of multidrug resistance in 46 newly diagnosed patients with acute leukemia.

OBJECTIVES: The aim of the present study was to assess the expression profile of multidrug resistance (MDR)-related proteins ABCB1, ABCC1 and LRP in 46 patients with acute leukemia (AL). METHODS: The levels of MDR gene mRNA expression and protein expression at diagnosis were analyzed by semi-quantitative PCR and flow cytometry, respectively. RESULTS: In the adult group, higher expression levels of abcc1 gene were associated with older age and lower levels of lactate dehydrogenase (LDH). In the pediatric group, abcc1 gene expression levels were associated with higher CD34 expression and a higher ABCB1 protein expression was correlated with high WBC counts. DISCUSSION/CONCLUSION: The present data indicate that abcb1 gene overexpression may be associated with a poor prognosis in adults with AL and that ABCB1 and abcc1 expression correlates with different prognostic factors in pediatric patients with AL. Our findings demonstrate that the method of choice to evaluate chemotherapy resistance-related proteins is a major variable.

Síndromes mielodisplásicas: aspectos moleculares, laboratoriais e a classificação OMS 2008 / Myelodysplasic symdrome: molecular and laboratorial aspects and the 2008 WHO classification

As síndromes mielodisplásicas (SMDs) são caracterizadas por uma desordem clonal de células primordiais (stem cell) e hematopoese ineficaz que levam à displasia de uma ou mais linhagens celulares da medula óssea, citopenias periféricas e instabilidade genética, as quais aumentam o risco de transformação à leucemia mieloide aguda. Esse grupo heterogêneo de doenças hematopoéticas pode surgir como doença primária, que possui etiologia variada e não completamente definida, ou secundária ao tratamento quimioterápico ou radioterápico para outras neoplasias. O surgimento e aprimoramento de tecnologias de diagnóstico geraram uma melhor compreensão dos processos envolvidos na gênese e evolução das SMDs, o que possibilitou o desenvolvimento de marcadores de diagnóstico e acompanhamentos cada vez mais precoces e específicos. No ano de 2008, a Organização Mundial da Saúde (OMS) redefiniu os critérios para classificação das SMDs, dividindo-as em sete subgrupos. Nessa classificação foram incluídos novos aspectos imunofenotípicos, genéticos, citomorfológicos e moleculares, o que tornou o domínio e o acesso a tecnologias de ponta imprescindíveis para a realização do diagnóstico das SMDs. Apesar dos avanços tecnológicos, alguns pontos, como as bases moleculares da transformação de SMD para LMA, ainda não estão bem esclarecidos, fazendo necessária a continuação de estudos nessa área. Diante disso, essa revisão busca compilar dados atuais dos aspectos moleculares e laboratoriais das SMDs.

Myelodysplastic syndromes (MDSs) are characterized by a stem cell clonal disorder and ineffective hematopoiesis which causes dysplasia in one or more bone marrow hematopoietic cell lineages, peripheral cytopenia and genetic instability with enhanced risk to transform into acute myeloid leukemia (AML). This heterogeneous group of hematopoietic diseases can develop as primary diseases, which posses a variable and not completely defined etiology, or as secondary to chemotherapy or radiotherapy for other neoplasias. The evolution of diagnostic tests has improved comprehension of the process involved in the genesis and evolution of MDSs, making the development of earlier and more specific tests for diagnosis and follow ups possible. In 2008, the World Health Organization (WHO) redefined the criteria for the classification of MDSs, dividing them into seven subgroups. This classification included new immunophenotypic, genetic, cytomorphologic and molecular features, which are essential for the diagnosis of MDSs and for a better comprehension of the disease. Despite technological advances, some details, such as the molecular basis of the transformation of MDS to AML, are still not completely understood, which makes further studies in this field necessary. Hence, the objective of this review is to make a compilation of recent molecular and laboratory aspects of MDS.

Diagnosticando depressão em pacientes internados com doenças hematológicas: prevalência e sintomas associados / Diagnosing depression among hematological impatients: prevalence and associated symptons

Introdução: não encontramos estudos avaliando o diagnóstico e a prevalência de depressão em pacientes hematológicos aqui no Brasil. Objetivo: verificar a prevalência dos sintomas depressivos e quais deles mais se associam à depressão em pacientes internados com doenças hematológicas. Métodos: num estudo transversal, 104 pacientes consecutivamente internados nos leitos da hematologia do Hospital Universitário da Universidade Federal de Santa Catarina (HU/UFSC) foram avaliados. Foram preenchidos questionários de variáveis sociodemográficas e de história psiquiátrica. O índice Charlson de co-morbidade (IC) foi usado para medir gravidade física. Foi aplicado, também, o inventário Beck de depressão (BDI). Aqueles que tiveram pontuação acima de 9 na soma dos 13 primeiros itens do BDI(BDI-13) foram considerados deprimidos. Também foi verificada a freqüência caso fosse utilizada a escala completa com 21 itens (BDI-21), com ponto de corte 16/17. Resultados: as prevalências foram: BDI-13 = 25% e BDI-21 = 32,7%. Após controle para fatores de confusão, os sintomas que permaneceram no modelo de regressão logística, indicando que melhor detectavam os deprimidos, foram sensação de fracasso, anedonia, culpa e fadiga. Conclusão: cerca de um quarto a um terço dos pacientes internados com doenças hematológicas tinham sintomas depressivos significativos, e os sintomas que melhor os discriminaram foram sensação de fracasso, anedonia, culpa e fadiga.