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.

Abstract Background: The emergence of oligoclonal bands, proteins differing from those originally identified at diagnosis, has been reported in multiple myeloma patients after high-dose chemotherapy followed by autologous stem cell transplantation and after successful conventional chemotherapy. The clinical relevance of oligoclonal bands remains unclear, but their emergence has been associated with better prognosis. The aim of the present study was to determine the prevalence, clinical characteristics and prognostic impact of the presence of oligoclonal bands in multiple myeloma patients. Methods: A retrospective cohort study was conducted. The study included newly diagnosed multiple myeloma patients with at least very good partial response after conventional dose or high-dose chemotherapy followed by autologous stem cell transplantation. The emergence of oligoclonal bands was identified using serum protein electrophoresis as well as serum and urine immunofixation techniques. Results: A total of 101 patients were included with a median follow-up of 42 months. In total, 55% were male, and the median age was 58 years (29-87 years). Fifty-one (50.5%) patients developed oligoclonal bands. They comprised 60% (45/75) of patients treated with autologous stem cell transplantation and 23% (6/26) of those who were not transplanted. Patients with oligoclonal bands showed better progression-free survival than those without the emergence of oligoclonal bands (p-value = 0.0075). Conclusion: The prevalence of oligoclonal bands in this study population was 50.5% with its frequency being greater in cases treated with autologous stem cell transplantation and in those attaining complete remission. Complete remission was more important than the emergence of oligoclonal bands on progression-free survival.

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.

ABSTRACT Background: Cyclophosphamide plus thalidomide as induction for multiple myeloma patients eligible for autologous stem cell transplantation may be a limiting factor for cell mobilization. The minimum acceptable mobilized peripheral blood stem cell count to prevent deleterious effects during transplantation is 2.0 × 106 CD34+ cells/kg. Combining other treatments to granulocyte-colony stimulating factor, such as cyclophosphamide, could overcome the mobilization limitation. The objective of this study was to assess the number of CD34+ cells mobilized using granulocyte-colony stimulating factor with and without cyclophosphamide after induction with cyclophosphamide, thalidomide and dexamethasone. Methods: A retrospective study was performed of a cohort of multiple myeloma patients submitted to autologous stem cell transplantations at two Brazilian centers between May 2009 and July 2013. The oral cyclophosphamide and thalidomide induction doses used were 1500 mg/month and 100-200 mg/day, respectively. Mobilization doses were 10-15 mcg/kg granulocyte-colony stimulating factor with 2-4 g/m2 cyclophosphamide, or 15-20 mcg/kg granulocyte-colony stimulating factor alone for 5 days. Collection of >2.0 × 106 CD34+ cells/kg was considered sufficient. Results: Eighty-eight patients were analyzed; only 18 received cyclophosphamide. The median age was 58 years old (range: 51-62) for the granulocyte-colony stimulating factor group and 56.5 years old (range: 54-60) for granulocyte-colony stimulating factor plus cyclophosphamide group. Fifty-two patients were male. Eighty cases (90.9%) were Durie-Salmon Staging System III-A/B and 38 (44.7%) and 20 cases (23.5%) were International Staging System 2 and 3, respectively. The group that received cyclophosphamide collected a higher median number of progenitor cells [3.8 (range: 3.1-4.4) vs. 3.2 (range: 2.3-3.8)] (p-value = 0.008). No correlation was observed between better responses or number of induction cycles and the number of cells collected. Conclusion: The number of cells mobilized with granulocyte-colony stimulating factor plus cyclophosphamide was higher. However, in both groups, the median number of CD34+ cells was sufficient to perform a single autologous stem cell transplantation; no deleterious effects were reported during harvesting.

ABSTRACT Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social-economic profile.

Abstract In addition to findings from conventional magnetic resonance imaging, modern magnetic resonance imaging techniques have provided important information about tumor metabolism, in vivo metabolite formation, water molecule diffusion, microvascular density, and blood-brain barrier permeability, all of which have improved the in vivo diagnostic accuracy of this method in the evaluation of primary central nervous system lymphoma. These nonconventional magnetic resonance techniques are useful in the clinical practice because they enhance conventional magnetic resonance imaging by reinforcing the possibility of a diagnosis and by allowing the early detection of disease recurrence. This report is a review of the most relevant contributions of nonconventional magnetic resonance techniques to the imaging diagnosis of primary central nervous system lymphoma, the differential diagnosis of this disease, and the prognosis of patients. This paper aims to describe a wide range of presentations of primary central nervous system lymphoma, their appearance in imaging, and the differential diagnoses of this disease.

OBJECTIVE: To demonstrate a correlation of C-reactive protein levels with disease stage and response to treatment in Hodgkin's lymphoma patients of the Hematology Service of Santa Casa de São Paulo.METHODS: A retrospective study based on review of medical records was carried out of 38 patients diagnosed with Hodgkin's lymphoma between October 2010 and December 2012. Three patients met the exclusion criteria, giving a final sample of 35 patients for analysis. C-reactive protein levels >1 mg/dL were considered positive.RESULTS: Among the patients analyzed, median age was 29 years, 65% were male and 85% had the classical nodular sclerosis subtype. Twenty-nine (82%) were in the advanced stage and 28% had bulky mass at diagnosis. Seventeen percent had bone marrow invasion by lymphoma. Baseline C-reactive protein levels were associated with both stage (p-value = 0.0035) and presence or absence of B symptoms (p-value = 0.008). The highest C-reactive protein levels were detected in patients with advanced disease while no patients with localized disease had C-reactive protein >5 mg/dL (p-value = 0.02). After the first treatment cycle, C-reactive protein fell to near-normal levels and no direct association with response pattern was found. As the mean follow-up was only 14 months, it was not possible to determine whether relapse was accompanied by a further increase in C-reactive protein.CONCLUSION: Baseline C-reactive protein levels directly correlated with stage and presence or absence of B symptoms, but the degree of improvement with treatment did not correlate with response pattern. After a longer follow-up, it may be possible to assess whether relapse correlates with a further increase in C-reactive protein levels.

CONTEXTO: Linfomas de tecido linfoide associado à mucosa (TLAM) são mais comumente encontrados no estômago, pulmões, órbita, glandulas salivares e tireoide. O envolvimento da traqueia é extremamente raro. RELATO DE CASO: Relato de caso raro de linfoma TLAM de traqueia, em mulher de 71 anos com tosse, dispneia, rouquidão e emagrecimento há um ano. Detectou-se lesão infiltrativa na porção média da traquéia. O diagnóstico anatomopatológico só foi obtido na biópsia do quinto procedimento endoscópico. A imunoquimioterapia R-COP (rituximabe, ciclofosfamida, vincristina e prednisona) induziu remissão completa dos sintomas e da lesão endoscópica. CONCLUSÕES: Linfoma TLAM de traqueia é uma doença indolente e extremamente rara, que deve ser considerada no diagnóstico diferencial das lesões de vias aéreas. O diagnóstico anatomopatológico por um patologista experimentado é fundamental. Imunoquimioterapia com R-COP levou à remissão completa da doença.

CONTEXT: Mucosa-associated lymphoid tissue (MALT) lymphomas are most commonly found in the stomach, lungs, orbital soft tissue, salivary glands and thyroid. Involvement of the trachea is extremely rare. CASE REPORT: This report describes a rare case of MALT lymphoma of the trachea in a 71-year-old woman who presented with a one-year history of coughing, dyspnea, hoarseness and weight loss. There was an infiltrative lesion in the mid-trachea. The anatomopathological diagnosis was only made from the fifth endoscopic biopsy attempt. Immunochemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisone (R-COP) induced complete remission of the symptoms and endoscopic lesion. CONCLUSIONS: MALT lymphoma of the trachea is extremely rare and indolent disease. It has to be considered in the differential diagnosis of airway lesions. It is crucial to obtain an anatomopathological diagnosis from a specialized pathologist. Immunochemotherapy with R-COP induced complete remission of the disease.

BACKGROUND: Iron deficiency is the most common disorder in the world, affecting approximately 25% of the world`s population and the most common cause of anemia. OBJECTIVE: To evaluate the efficacy and safety of intravenous iron sucrose (IS) in the treatment of adults with iron deficiency anemia METHODS: Eighty-six adult patients with iron deficiency anemia, who had intolerance or showed no effect with oral iron therapy, received a weekly dose of 200 mg of intravenous iron sucrose until the hemoglobin level was corrected or until receiving the total dose of intravenous iron calculated for each patient RESULTS: The mean hemoglobin and serum ferritin levels were 8.54 g/dL and 7.63 ng/mL (pre-treatment) and 12.1 g/dL and 99.0 ng/mL (post-treatment) (p-value < 0.0001), respectively. The average increases in hemoglobin levels were 3.29 g/dL for women and 4.58 g/dL for men; 94% of male and 84% of female patients responded (hemoglobin increased by at least 2 g/dL) to intravenous iron therapy. Correction of anemia was obtained in 47 of 69 (68.1%) female patients and in 12 of 17 male (70.6%) patients. A total of 515 intravenous infusions of iron sucrose were administered and iron sucrose was generally well tolerated with no moderate or serious adverse drug reactions recorded by the investigators. CONCLUSIONS: Our data confirm that the use of intravenous iron sucrose is a safe and effective option in the treatment of adult patients with iron deficiency anemia who lack satisfactory response to oral iron therapy. Intravenous iron sucrose is well tolerated and with a clinically manageable safety profile when using appropriate dosing and monitoring. The availability of intravenous iron sucrose would potentially improve compliance and thereby reduce morbidities from iron deficiency.

A hemocromatose hereditária (HH) está relacionada a diversos distúrbios do metabolismo do ferro que ocasionam sua sobrecarga tecidual. A HH clássica está associada às mutações do gene HFE (homozigose para C282Y ou duplo heterozigose para C282Y/H63D), sendo encontrada quase exclusivamente em descendentes do norte Europeu. A hemocromatose hereditária, quando não relacionada ao gene HFE, é causada por mutações de outros genes, recentemente identificados, envolvidos no metabolismo do ferro. Hepcedina é o hormônio regulador do ferro que inibe a ferroportina, proteína exportadora de ferro dos enterócitos e dos macrófagos; um defeito na expressão do gene da hepcedina ou na sua função costuma ser a causa da maioria dos tipos de hemocromatose hereditária. Os alvos acometidos pela HH são órgãos e tecidos - fígado, coração, pâncreas, articulações e pele -, sendo a cirrose e o diabetes melito os sinais tardios da doença em pacientes com expressivo aumento da concentração hepática de ferro. Pacientes com diagnóstico estabelecido de hemocromatose hereditária e sobrecarga de ferro devem ser tratados com flebotomia para a obtenção de depleção do ferro do organismo; em seguida, com flebotomia de manutenção. As causas mais frequentes de morte por hemocromatose hereditária são câncer hepático, cirrose, miocardiopatia e diabete; entretanto, pacientes submetidos à depleção do ferro de maneira satisfatória e antes do desenvolvimento da cirrose ou da diabete podem ter sobrevida normal.

Hereditary hemochromatosis refers to several inherited disorders of the iron metabolism that lead to tissue iron overload. Classical hereditary hemochromatosis is associated with mutations of the HFE gene (C282Y homozygotes or C282Y/H63D compound heterozygotes) and is almost exclusively found in populations of northern European descent. Non-HFE-associated hereditary hemochromatosis is caused by mutations in other recently identified genes involved in the iron metabolism. Hepcidin is an iron regulatory hormone that inhibits ferroportin-mediated iron export from enterocytes and macrophages. Defective hepcidin gene expression or function may underlie most forms of hereditary hemochromatosis. Target organs and tissues affected by hereditary hemochromatosis include the liver, heart, pancreas, joints, and skin, with cirrhosis and diabetes melittus representing late signs of disease in patients with very high liver iron concentrations. Patients with an established diagnosis of hereditary hemochromatosis and iron overload should be treated with phlebotomy to achieve body iron depletion followed by maintenance phlebotomy. The most frequent causes of death in hereditary hemochromatosis are liver cancer, cirrhosis, cardiomyopathy, and diabetes. However, patients who undergo successful iron depletion before developing cirrhosis or diabetes can have normal life expectancy.

OBJETIVOS: Estimar a prevalência da infecção pelo Helicobacter pylori (HP) e determinar os fatores associados, em adultos saudáveis, doadores voluntários de medula óssea em São Paulo, Brasil. MÉTODOS: 248 indivíduos saudáveis, residentes na zona urbana de São Paulo, responderam a um questionário relatando condições sociais e domiciliares na infância e na vida adulta, assim como antecedentes gastrintestinais e principais fatores associados à infecção. Amostras de sangue foram coletadas e o soro foi analisado utilizando um teste de ELISA previamente validado. RESULTADOS: A prevalência da infecção pelo HP em 248 doadores foi de 48,8%, IC95%= [45,6; 52,0]. Na análise univariada, a infecção pelo HP esteve significativamente associada à ausência de água encanada (p=0,040), a escolaridade da mãe (p=0,005) e do indivíduo (p<0,001). Na análise múltipla, os fatores independentes foram a escolaridade da mãe e do indivíduo. CONCLUSÕES: A prevalência de infecção de 48,8% mostra que na região urbana de São Paulo, onde há água tratada e esgoto encanado, temos uma prevalência semelhante à encontrada em países industrializados. O fator de maior significância para a aquisição do HP foi a escolaridade, seja individual ou materna, o que sugere que os hábitos higiênicos e comportamentais possam ser determinantes da infecção.

OBJECTIVES: The purpose of this study was to estimate the prevalence of Helicobacter pylori (HP) infection and evaluate symptoms and factors associated with HP infection in bone marrow donors, in São Paulo, Brazil. METHODS: 248 healthy individuals from urban sites of São Paulo, answered a questionnaire on social and housing conditions in childhood and adult life, as well as clinical gastrointestinal background and main risk factors. Blood samples were collected and serum was tested using a validated ELISA assay. RESULTS: HP prevalence was 48.8%, 95% CI=[45.6; 52.0]. In the univariate analysis, significant associations were found between HP seroprevalence and water supply (p=0.040), maternal (p=0.005) and individual education (p<0.001). Multiple analysis has shown that maternal and individual education were independent risk factors for the infection. CONCLUSIONS: The results have shown that São Paulo's urban sites provided with water supply and sewage systems have similar HP prevalence as industrialized countries. The main risk factors for HP infection were maternal and individual education, which suggests that hygiene and personal habits are determinant to the infection.

OBJETIVOS: Estimar a prevalência da infecção pelo Helicobacter pylori (HP) e determinar os fatores associados, em adultos saudáveis, doadores voluntários de medula óssea em São Paulo, Brasil. MÉTODOS: 248 indivíduos saudáveis, residentes na zona urbana de São Paulo, responderam a um questionário relatando condições sociais e domiciliares na infância e na vida adulta, assim como antecedentes gastrintestinais e principais fatores associados à infecção. Amostras de sangue foram coletadas e o soro foi analisado utilizando um teste de ELISA previamente validado. RESULTADOS: A prevalência da infecção pelo HP em 248 doadores foi de 48,8%, IC95%= [45,6; 52,0]. Na análise univariada, a infecção pelo HP esteve significativamente associada à ausência de água encanada (p=0,040), a escolaridade da mãe (p=0,005) e do indivíduo (p<0,001). Na análise múltipla, os fatores independentes foram a escolaridade da mãe e do indivíduo. CONCLUSÕES: A prevalência de infecção de 48,8% mostra que na região urbana de São Paulo, onde há água tratada e esgoto encanado, temos uma prevalência semelhante à encontrada em países industrializados. O fator de maior significância para a aquisição do HP foi a escolaridade, seja individual ou materna, o que sugere que os hábitos higiênicos e comportamentais possam ser determinantes da infecção.

OBJECTIVES: The purpose of this study was to estimate the prevalence of Helicobacter pylori (HP) infection and evaluate symptoms and factors associated with HP infection in bone marrow donors, in São Paulo, Brazil. METHODS: 248 healthy individuals from urban sites of São Paulo, answered a questionnaire on social and housing conditions in childhood and adult life, as well as clinical gastrointestinal background and main risk factors. Blood samples were collected and serum was tested using a validated ELISA assay. RESULTS: HP prevalence was 48.8%, 95% CI=[45.6; 52.0]. In the univariate analysis, significant associations were found between HP seroprevalence and water supply (p=0.040), maternal (p=0.005) and individual education (p<0.001). Multiple analysis has shown that maternal and individual education were independent risk factors for the infection. CONCLUSIONS: The results have shown that São Paulo's urban sites provided with water supply and sewage systems have similar HP prevalence as industrialized countries. The main risk factors for HP infection were maternal and individual education, which suggests that hygiene and personal habits are determinant to the infection.

CONTEXTO E OBJETIVO: Hemocromatose é um distúrbio hereditário comum do metabolismo do ferro e uma das causas mais importantes de sobrecarga de ferro. O objetivo foi analisar a presença das mutações C282Y, H63D e S65C no gene HFE e dos alelos HLA-A em um grupo de pacientes brasileiros com sobrecarga de ferro e correlacionar o genótipo com variáveis clínicas e laboratoriais. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, na Disciplina de Hematologia e Oncologia. Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. MÉTODOS: Estudamos 35 pacientes com sobrecarga de ferro atendidos em nosso ambulatório entre janeiro de 2001 e dezembro de 2003. Ferro sérico, ferritina sérica e capacidade total de ligação de ferro foram determinados por técnicas convencionais. As mutações C282Y, H63D e S65C do gene HFE e a determinação dos alelos HLA-A foram realizadas por reação de polimerase em cadeia (PCR). RESULTADOS: Vinte e seis dos 35 pacientes (74%) apresentavam pelo menos uma das mutações analisadas do gene HFE. Entre esses, cinco (14%) com genótipo C282Y/C282Y, 4 (11%) C282Y/H63D, 1 (3%) H63D/H63D, 6 (17%) C282Y/WT e 10 (29%) H63D/WT. Não foi encontrado nenhum paciente com a mutação S65C e 9 (26%) pacientes não apresentavam nenhuma das três mutações do gene HFE. Quatro dos 5 pacientes com genótipo C282Y/C282Y (80%) e 3 dos 4 pacientes C282Y/H63D (75%) eram HLA A*03. CONCLUSÃO: Análise das mutações do gene HFE constitui um importante procedimento na identificação de pacientes com hemocromatose hereditária, particularmente em pacientes com sobrecarga de ferro.

CONTEXT AND OBJECTIVE: Hemochromatosis is a common inherited disorder of iron metabolism and one of the most important causes of iron overload. The objective was to analyze the presence of C282Y, H63D and S65C mutations in the HFE gene and HLA-A alleles for a group of Brazilian patients with iron overload, and to correlate genotype with clinical and laboratory variables. DESIGN AND SETTING: Prospective study, in Discipline of Hematology and Oncology, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. METHODS: We studied 35 patients with iron overload seen at our outpatient unit between January 2001 and December 2003. Fasting levels of serum iron and ferritin, and total iron-binding capacity, were assayed using standard techniques. Determinations of C282Y, H63D and S65C mutations in the HFE gene and of HLA-A alleles were performed by polymerase chain reaction (PCR). RESULTS: Twenty-six out of 35 patients (74%) presented at least one of the HFE gene mutations analyzed. Among these, five (14%) were C282Y/C282Y, four (11%) C282Y/H63D, one (3%) H63D/H63D, six (17%) C282Y/WT and ten (29%) H63D/WT. No patients had the S65C mutation and nine (25%) did not present any of the three HFE mutations. Four out of five patients with C282Y/C282Y genotype (80%) and three out of four patients with C282Y/H63D genotype (75%) were HLA A*03. CONCLUSION: Analysis of HFE gene mutations constitutes an important procedure in identifying patients with hereditary hemochromatosis, particularly for patients with iron overload.