BCL-2 Inhibition as Treatment for Chronic Lymphocytic Leukemia.

OPINION STATEMENT: At the end of the 1990s, with the advent of imatinib for chronic myeloid leukemia and rituximab for B cell lymphoproliferative diseases with CD20 expression, there was a great conceptual evolution in the treatment of onco-hematological diseases. Researchers from around the world and the pharmaceutical industry began to focus their efforts on the so-called target therapy used alone or associated with classic chemotherapeutic drugs. In chronic lymphocytic leukemia, the development of second-generation anti-CD20 antibodies, biosimilars, PI3K (phosphatidylinositol 3-kinases) inhibitors, BTK (Bruton's tyrosine kinase) inhibitors, and anti-bcl 2 drugs represented mainly by venetoclax brought new, broader, and more effective opportunities in the treatment of this disease. This breakthrough occurred mainly regarding patients with alteration in 17p or mutation of the p53 gene for whom selecting the new drugs that act on B cell signaling (BTK and PI3K inhibitors) in the first line is mandatory. In fit patients with immunoglobulin heavy chain mutation, it is still acceptable to use the chemotherapy regimen with fludarabine, cyclophosphamide, and rituximab (FCR) and, in those who do not fit or are not IgVH-mutated, bendamustine-rituximab regimen. However, the first-line use of ibrutinib or venetoclax associated with immunotherapy within the concepts of infinite (ibrutinib) or finite (venetoclax) treatment has been increasingly used. In the second line, venetoclax, ibrutinib, and idelalisib have become the preferred treatments. I believe that a process of instruction and decision shared with patients considering the risks-benefits-cost and access to treatments should guide the choices within these concepts. Another fundamental aspect to discuss is the objective of the treatment for chronic lymphocytic leukemia (CLL) for a specific patient: the increase progression-free survival and overall survival and/or the achievement of minimal residual disease. CLL is the most common leukemia in adults with a median age at diagnosis of 72 years. The clinical course is heterogeneous, and outcomes are influenced by individual clinical presentation and disease biology. Molecular and genomic factors, including fluorescence in situ hybridization (FISH) testing, karyotype, and immunoglobulin heavy chain variable region gene (IGHV) mutational status, are important to treatment decisions and to predict the clinical course. However, despite disease biology, the presence of active disease is the most important criteria to initiate treatment. In the past decade, target therapies that inhibit B cell receptor signaling pathways and, more recently, BCL2 antagonists have emerged as a new treatment paradigm: chemo-free with fixed duration therapy. Bruton's tyrosine kinase inhibitors (BTK) are a class of oral medications approved for frontline and relapsed disease, effective for achieving lasting response and disease control with a good safety profile. BTK inhibitors are an attractive option for high-risk patients who are not candidates for an intensive regimen. However, it is a continuous therapy, and drug resistance or severe adverse events could lead to treatment suspension. BCL2 antagonists are an attractive alternative to BTK inhibitors. Anti-apoptotic BCL2 is associated with tumor genesis and chemotherapy resistance. The BCl2, an anti-apoptotic protein located in the mitochondrial membrane, is a major contributor to the pathogenesis of lymphoid malignancies and is overexpressed in CLL cells promoting clonal cell survival. Venetoclax is a potent and selective member of the BH3 mimetic drugs and a physiologic antagonist of BCL2. Venetoclax has demonstrated quick and durable responses in naïve and relapsed or refractory CLL (r/r CLL) patients, including high-risk patients. Furthermore, it has shown deeper responses, achieving a higher incidence of negative minimal residual disease (MRD) with a fixed duration therapy. In the past decade, there was a remarkable progress in CLL treatment. However, neither of the new target therapies is considered curative or free of toxicity. This article will focus on the treatment approach of CLL patients with BCl2 antagonists. Treatment strategy (combined versus monotherapy; continuous versus limited duration therapy), toxicity profile, and future directions will be exposed in this review.

How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation

ABSTRACT: The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.

How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation.

The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.

Risk factors and incidence of thrombosis in a Brazilian cohort of patients with Philadelphia-negative myeloproliferative neoplasms.

Few data are available regarding epidemiology and outcomes of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) in Latin America. Therefore, current models for MPN treatment are based in large cohorts of patients from Europe and North America. In this paper, we conducted a retrospective study to evaluate thrombotic and bleeding events in a cohort of patients with MPN from a reference center in Brazil. A total of 334 patients were included, being essential thrombocythemia the most common diagnosis. Here, we found that 41% of the MPN patients had a thrombotic event prior to the diagnosis. Thrombosis was more frequent in patients under 60 years-old. In a multivariable model, only JAK2 V617F mutation (OR 2.57 95% CI 1.58-4.18, p < 0.001) and presence of two cardiovascular risk factors (OR 1.90 95% CI 1.21-2.98, p < 0.005) were significant for thrombosis. The risk of thrombosis was similar among all subtypes of MPN. Cumulative incidence of thromboembolic event at 5 years from diagnosis was 5.8% (95% CI 3.5-8.9), which is similar to previous studies. The high incidence of thromboembolic events in younger patients suggests that socioeconomic disparities might have a role in the outcomes of MPN.

Síndrome de La Tourette: revisão de literatura / Tourette syndrome: review of literature

INTRODUÇÃO: A Síndrome de La Tourette (ST) foi descrita pela primeira vez em 1825 e se trata de uma patologia neuropsiquátrica de início geralmente na infância, que acomete mais o sexo masculino, caracterizada por notável comprometimento psicológico e social, causando impacto na vida dos portadores e familiares. Até pouco tempo, essa patologia era considerada uma condição rara, porém, estudos atuais demonstram que a taxa de prevalência pode variar de 1 por cento a 2,9 por cento em alguns grupos. OBJETIVO: Realizar uma revisão de literatura sobre os principais aspectos relacionados à Síndrome de La Tourette. SÍNTESE DOS DADOS: A ST é um distúrbio genético, associado a alterações neurofisiológicas e neuroanatômicas, caracterizado por fenômenos compulsivos, cuja etiologia ainda é desconhecida. O quadro clínico é composto, principalmente, por tiques motores e vocais que se subdividem em simples e complexos. A sua associação com Transtorno Obsessivo Compulsivo e Transtorno do Déficit de Atenção e Hiperatividade é relativamente comum. O diagnóstico é eminentemente clínico e não existe, até o momento, nenhum teste laboratorial específico que confirme esta patologia. O tratamento é fundamentado, principalmente, na terapia psicológica. Porém, quando há necessidade do emprego de fármacos, os mais utilizados são os antagonistas dos receptores de dopamina. CONCLUSÃO: A ST causa diversos prejuízos psicossociais e educacionais para o indivíduo e familiares. Porém, o diagnóstico e tratamento precoces são capazes de minimizar ou anular estes danos. Desta forma, conhecer os aspectos gerais que norteiam a ST é de fundamental importância para preservar a qualidade de vida dos portadores da doença.

INTRODUCTION: Tourette Syndrome (TS) was described for the first time in 1825, and it is a neuropsychiatry disease, initially begins in childhood, affects more males, characterized by remarkable social and psychological commitment, impacting the lives of patients and family. Until recently, this disease were considered a rare condition, but current studies show that the prevalence rate may vary in 1 percent to 2,9 percent in a few groups. OBJECTIVE: Perform a review of literature over the main aspects related to Tourette syndrome. DATA SYNTHESIS: The TS is a genetic disorder, associated with neuroanatomical and neurophysiological alterations, characterized by compulsive phenomenon, whose etiology is still unknown. The clinical profile is composed, mostly, by motor tics and vocal tics, that which are divided in simple and complex. Its association with Obssessive Compulsive Disorder and Attention Deficit Hyperactivity Disorder is very commom. The diagnosis is mainly clinical and do not exist. Until now, there is no specific laboratory test that confirm this pathology. The treatment is based mainly on psychological theory. However when there is need for the use of drugs, the most widely used are the antagonists of dopamine receptors. CONCLUSION: The TS causes many damages as psychosocial and educational for the individual and the family. However, the diagnosis and the early treatment are able to minimize or cancel this damages. This way, knowing the general aspects that guide the TS is of utmost importance to preserve the quality of life for the patients with the disease.

Main vocal complaints of elderly patients after leprosy treatment.

UNLABELLED: Leprosy is an infectious disease, with vocal involvement varying between hoarseness and difficult breathing. AIM: Compare the main vocal complaints among elderly patients after treatment for leprosy and a control group. STUDY DESIGN: Descriptive prospective. MATERIALS AND METHODS: We included 50 patients aged over 60 years, 32 had been treated for leprosy, and the others formed the control group. We used our own questionnaire to analyze the vocal symptoms presented by the two groups, as well as gender, age, life style and comorbidities. RESULTS: Among the treated group, the most frequent symptoms were hawk (34.4%) and hoarseness (28.1%), while in the control group the most prevalent symptoms were hoarseness (77.8%) and a foreign body sensation (55.6%). CONCLUSION: The most prevalent voice complaints in patients treated for leprosy are hawking and hoarseness, and that its development is influenced by life style and associated diseases.

Principais queixas vocais de pacientes idosos pós-tratamento para hanseníase / Main vocal complaints of elderly patients after leprosy treatment

A hanseníase é uma doença infecto-contagiosa, cujo comprometimento vocal manifesta-se desde rouquidão à dificuldade respiratória. OBJETIVO: Comparar as principais queixas vocais entre pacientes idosos pós-tratamento para hanseníase e um grupo controle. FORMA DE ESTUDO: Descritivo prospectivo. MATERIAL E MÉTODO: Foram incluídos 50 pacientes com idade superior a 60 anos; 32 haviam sido tratados para hanseníase e os demais constituíram o grupo-controle. Houve aplicação de questionário próprio, sendo analisados os sintomas vocais apresentados pelos dois grupos,assim como sexo, faixa etária, hábitos de vida e comorbidades. RESULTADOS: Dentro do grupo pós-tratamento, os sintomas mais frequentes foram pigarro (34,4 por cento) e rouquidão (28,1 por cento), enquanto que no grupo controle os sintomas mais prevalentes foram pigarro (77,8 por cento) e sensação de corpo estranho (55,6 por cento). CONCLUSÃO: Os sintomas vocais mais prevalentes em pacientes pós-tratamento para hanseníase são o pigarro e a rouquidão e sua evolução é influenciada pelos hábitos de vida e por doenças associadas.

Leprosy is an infectious disease, with vocal involvement varying between hoarseness and difficult breathing. AIM: compare the main vocal complaints among elderly patients after treatment for leprosy and a control group. STUDY DESIGN: descriptive prospective. MATERIALS AND METHODS: We included 50 patients aged over 60 years, 32 had been treated for leprosy, and the others formed the control group. We used our own questionnaire to analyze the vocal symptoms presented by the two groups, as well as gender, age, life style and comorbidities. RESULTS: among the treated group, the most frequent symptoms were hawk (34.4 percent) and hoarseness (28.1 percent), while in the control group the most prevalent symptoms were hoarseness (77.8 percent) and a foreign body sensation (55.6 percent). CONCLUSION: the most prevalent voice complaints in patients treated for leprosy are hawking and hoarseness, and that its development is influenced by life style and associated diseases.

Perfis de mães que amamentaram exclusivamente por seis meses e daquelas que realizaram desmame precoce / Profiles of mothers who had suckled exclusively for six months and of that they had carried through weans precocious

Analisa o perfil socioeconômico e cultural das mães que amamentaram adequadamente seus filhos e daquelas que não o fizeram. Estudo transversal,cujos dados foram coletados mediante aplicação de protocolo próprio, foram incluídas 100 mães cadastradas na Casa Família Água Cristal no período de agosto a novembro de 2006.