OBJECTIVES: Oral mucositis is a complication frequently associated with hematopoietic stem cell transplantation, decreasing a patient's quality of life and increasing the occurrence of opportunistic infections. The purpose of this study was to determine the incidence and severity of oral mucositis and to assess the correlation of this disease with the oral health of an individual at the time of hematopoietic stem cell transplantation. METHODS: Before transplantation, patients' oral health and inflammatory conditions were determined using the gingival index and the plaque index, which are based on gingival bleeding and the presence of dental plaque, respectively. Additionally, the dental health status was determined using the decayed, missing, and filled teeth index. The monitoring of oral mucositis was based on the World Health Organization grading system and was performed for five periods: from Day 0 to D+5, from D+6 to D+10, from D+11 to D+15, from D+16 to D+20, and from D+21 to D+30. RESULTS: A total of 97 patients (56% male and 44% female) who underwent hematopoietic stem cell transplantation at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo between January 2008 and July 2009 were prospectively examined. The incidence of ulcerative mucositis was highest from days +6 to +10 and from days +11 to +15 in the patients who underwent autologous and allogeneic hematopoietic stem cell transplantation, respectively. CONCLUSION: The data, including the dental plaque and periodontal status data, showed that these oral health factors were predictive of the incidence and severity of oral mucositis in a cohort of patients with similar conditioning regimens before hematopoietic stem cell transplantation.

OBJECTIVE: Celiac disease is a permanent enteropathy caused by the ingestion of gluten, which leads to an immunemediated inflammation of the small intestine mucosa. The prevalence of celiac disease varies among different nations and ethnic backgrounds, and its diversity is determined by genetic and environmental factors. São Paulo city is one of the largest cities in the world, with a vast population and an important history of internal migratory flow from other Brazilian regions, as well as immigration from other, primarily European, countries, resulting in significant miscegenation. The aim of the present study was to estimate the prevalence of adults with undiagnosed celiac disease among blood donors of São Paulo by collecting information on the ancestry of the population studied. METHODS: The prevalence of celiac disease was assessed by screening for positive IgA transglutaminase and IgA endomysium antibodies in 4,000 donors (volunteers) in the Fundação Pró-Sangue Blood Center of São Paulo, São Paulo, Brazil. The antibody-positive subjects were asked to undergo a small bowel biopsy. RESULTS: Of the 4,000 subjects, twenty-four had positive tests, although both antibody tests were not always concordant. For example, ten subjects were positive for IgA tissue transglutaminase only. In twenty-one positive patients, duodenal biopsies were performed, and the diagnosis of celiac disease was confirmed in fourteen patients (Marsh criteria modified by Oberhuber). In this group, 67% claimed to have European ancestry, mainly from Italy, Portugal and Spain. CONCLUSION: The prevalence of celiac disease is at least 1:286 among supposedly healthy blood bank volunteers in São Paulo, Brazil.

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4x10(9)/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment dueto liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation with HLA-identical donors has been established for the treatment of acute myeloid leukemia patients for over 30 years with a cure rate of 50% to 60%. OBJECTIVES: To analyze the overall survival of patients and identify factors that influence the outcomes of this type of transplant in patients in 1st complete remission who received a busulfan and melphalan combination as conditioning regimen. METHODS: Twenty-five consecutive patients with acute myeloid leukemia were enrolled between 2003 and 2008. The median age was 34 years old (Range: 16 - 57 years). All patients received cyclosporine and methotrexate for prophylaxis against graft-versus-host disease. Median neutrophil engraftment time was 16 days (Range: 7 - 22 days) and 17 days (Range: 7 - 46 days) for platelets. Sinusoidal obstructive syndrome was observed in three patients, seven had grade II acute graft-versus-host disease and one extensive chronic graft-versus-host disease. RESULTS: The overall survival by the Kaplan-Meier method was 48% after 36 months with a plateau at 36 months after transplantation. Intensive consolidation with high-dose arabinoside resulted in an improved survival (p-value = 0.0001), as did grade II acute graft-versus-host disease (p-value = 0.0377) and mild chronic graft-versus-host disease (p-value < 0.0001). Thirteen patients died, five due to infection within 100 days of transplant, two due to hemorrhages, one to infection and graftversus-host disease and three relapses followed by renal failure (one) and infection (two). The cause of death could not be determined for two patients. CONCLUSION: The busulfan and melphalan conditioning regimen is as good as other conditioning regimens providing an excellent survival rate.

BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported.

A case of a follicular lymphoma transformed into a CD20+ is described which progressed with the loss of CD20 expression after 8 cycles of R-CHOP. This phenomenon is not a rare event and has shown poor prognosis. Our purposes are to describe this event and suggest biopsy in relapsed or progressive disease.

CONTEXTO E OBJETIVO: A expressão gênica e imunoistoquímica do linfoma difuso de grandes células B (LDGCB) vem permitindo a identificação de importantes subgrupos prognósticos: LDGCB do centro germinativo (CG) e LDGCB de células B ativadas (CBA). Entretanto, existem poucos dados disponíveis com LDGCB de alto risco, sendo o prognóstico dos LDGCB do CG melhor que os LDGCB de CBA. A participação do Bcl-2 como preditor de sobrevida nos LDGCB não é clara e sua expressão é variável entre os dois subgrupos de LDGCB. Neste estudo é avaliada a frequência e o prognóstico da expressão da proteína Bcl-2 em LDGCB de alto risco. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo realizado entre portadores de LDGCB tratados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foi avaliado o impacto prognóstico da expressão das proteínas CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) e Bcl-2 por imunoistoquímica em LDGCB de alto risco. Foram avaliados, para todos os marcadores, 73 pacientes com idade de 18 a 60 anos. RESULTADOS: Vinte e quatro (32,9%) pacientes foram classificados como LDGCB do CG e 49 (67,1%) como LDGCB de CBA, sem diferença nas taxas de remissão completa, sobrevida livre de doença e sobrevida global. Vinte e sete (37%) apresentaram expressão de Bcl-2, o qual foi o único fator preditivo independente de pior prognóstico de sobrevida global à análise multivariada. CONCLUSÃO: A expressão da proteína Bcl-2 ocorreu em 37% dos portadores de LDGCB de alto risco, sem diferença entre os subgrupos de LDGCB do CG ou de CBA.

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9%) were GCB-like and 49 (67.1%) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37%) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37% of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

A neutropenia febril (NF) é uma complicação frequente e potencialmente fatal nos pacientes em tratamento quimioterápico. Entendemos hoje que a neutropenia febril é considerada uma emergência clínica e que a administração de antibióticos de amplo espectro diminui drasticamente a mortalidade. Estudos sugerem que a neutropenia febril compreende um grupo extremamente heterogêneo e que dados clínicos como febre domiciliar, ausência de hipotensão, ausência de desidratação, ausência de doença pulmonar obstrutiva crônica, ausência de outros sintomas, ausência de infecção fúngica prévia e idade < 60 anos são fatores de proteção para complicações clínicas graves segundo o estudo da Multinational Association for Supportive Care of Cancer (MASCC). Estes dados permitem maior segurança para o tratamento ambulatorial e alta precoce, uma vez que estudos fármaco-econômicos demonstram importante redução de custos no tratamento ambulatorial da neutropenia febril. O objetivo desta revisão é discutir instrumentos de segurança da triagem de um paciente neutropênico febril (principalmente pela utilização do índice MASCC), como também demonstrar as formas descritas na literatura do tratamento ambulatorial e seus resultados.

Febrile neutropenia is a frequent and potentially fatal adverse event of chemotherapy. Nowadays, febrile neutropenia is considered an emergency and it is known that prompt infusion of antibiotics decreases mortality. Several studies demonstrated that febrile neutropenia is a heterogeneous group of diseases and that factors such as outpatient status, no hypotension, no dehydration, no chronic obstructive pulmonary disease, no symptoms, no previous fungal infection and age < 60 years are protective factors against serious complications as demonstrated by the Multinational Association for Supportive Care in Cancer (MASCC). These data show that outpatient treatment and early discharge is safer and much research has shown lower costs for outpatient treatment in low-risk patients with febrile neutropenia. The aim of this work is to review and discuss tools (in particular the MASCC index) for safe screening of febrile neutropenia for outpatient treatment in addition to demonstrate results of research.

Os linfomas de células B indolentes representam aproximadamente 40% do total de linfomas não Hodgkin (LNHs). O avanço das tecnologias novas tem contribuído para a melhora no diagnóstico e classificação dos LNH indolentes. O linfoma folicular é o mais comum e sua frequência varia significantemente pelo mundo. Adescrição do Índice Internacional de Prognóstico dos linfomas folicular (FLIPI) representa um passo importante na identificação de subgrupos de pacientes, mas seu uso na prática clínica ainda necessita ser estabelecido. O uso de um número maior de anticorpos monoclonais para imunoistoquímica, estudo citogenético incluindo citogenética convencional ou hibridização in-situ por fluorescência (FISH), bem como o desenvolvimento de técnicas de alta resolução incluindo a expressão por microarray possibilita maior acurácia no diagnóstico e definição precisa dos biomarcadores com valor na estratificação de risco. A identificação de genes específicos para os diversos tipos de linfomas permite o reconhecimento de potenciais proteínas alvo que podem ser validadas usando imunoistoquímica. Análises da expressão do perfil de genes ou variações genéticas constitutivas pode também prover conhecimentos adicionais para o prognóstico em um futuro próximo. Um entendimento da biologia desses distintos tumores linfoides permite-nos identificar novos grupos de genes relacionados à doença e deve facilitar o desenvolvimento diagnóstico, predizendo a evolução e permitindo tratamentos personalizados.

Indolent B-cell lymphomas account for approximately 40% of all non-Hodgkin lymphomas (NHLs). Advances in technology have contributed to improvements in the diagnosis and classification of indolent non-Hodgkin lymphomas. Follicular Lymphomas are the most common although the frequency varies significantly throughout the world. The description of the Follicular Lymphoma International Prognostic Index (FLIPI) was an important step in identifying patient subgroups, but its use in the clinical practice has not been established yet. The use of a larger number of paraffin active monoclonal antibodies for immunohistochemistry, molecular cytogenetic studies including standard cytogenetics, multi-color fluorescence in-situ hybridization (FISH), polymerase chain reaction and locus-specific fluorescence insitu hybridization as well as developments in high-resolution techniquesincluding microarray gene expression profiling allow more accurate diagnosis andprecise definition of biomarkers of value in risk stratification. The identification ofdiseasespecific gene lists resulting from expression profiling provides a number ofpotential protein targets that can be validated using immunohistochemistry. Analysesof gene expression profiles or constitutive gene variations may also provide additional insight for prognostication in the near future. A comprehensive understanding of the biology of these distinct lymphoid tumors will allow us to identify novel diseaserelated genes and should facilitate the development of improved diagnosis, outcome prediction, and personalized approaches to treatment.

Anti-U é um aloanticorpo eritrocitário raro detectado exclusivamente em negros, que pode causar doença hemolítica do recém-nascido e reações transfusionais hemolíticas. Relatamos o caso de um recém-nascido, de sexo feminino, que apresentou teste de antiglobulina direto fortemente positivo, dirigido a um anticorpo IgG em sangue de cordão umbilical. Anti-U foi identificado por técnica de eluição ácida. A mãe apresentava pesquisa de anticorpos irregulares positiva com anticorpo anti-U, de subclasses IgG1 e IgG3, título 32, identificado ao nascimento. O ensaio de monocamada de monócitos apresentou resultado positivo (3.1%), mostrando uma interação moderada de receptores Fc com soro materno. O recém-nascido foi tratado somente por fototerapia durante 48 horas para uma doença hemolítica leve. A criança recuperou-se bem e teve alta médica no quarto dia de vida. Concluímos que quando um anticorpo contra um antígeno eritrocitário de alta freqüência for identificado em gestantes negras e pardas, anti-U deve ser investigado.

Anti-U is a rare red blood cell alloantibody that has been found exclusively in blacks. It can cause hemolytic disease of the newborn and hemolytic transfusion reactions. We describe the case of a female newborn presenting a strongly positive direct antiglobulin test due to an IgG antibody in cord blood. Anti-U was recovered from cord blood using acid eluate technique. Her mother presented positive screening of antibodies with anti-U identified at delivery. It was of IgG1 and IgG3 subclasses and showed a titer of 32. Monocyte monolayer assay showed moderate interaction of Fc receptors with maternal serum with a positive result (3.1%). The newborn was treated only with 48 hours of phototherapy for mild hemolytic disease. She recovered well and was discharged on the 4th day of life. We conclude that whenever an antibody against a high frequency erythrocyte antigen is identified in brown and black pregnant women, anti-U must be investigated.

As escassas informações sobre histologia hepática na co-infecção do vírus da Hepatite C (VHC) e vírus da Hepatite G (VHG) nos levou a investigar o RNA-VHG em 46 doadores de sangue com hepatite C, dos quais 22 com biópsia hepática: co-infecção VHC / VHG (n = 6) e infecção isolada do VHC (n = 16). Além de estadiamento e gradação da atividade inflamatória nas áreas portal, peri-portal e lobular, segundo o Consenso Brasileiro, calculamos também o índice de progressão da fibrose. Os pacientes estudados não apresentavam sintomas ou sinais físicos de doença hepática. A prevalência da co-infecção VHC / VHG foi de 15,2%. A maior parte dos pacientes apresentava-se com lesão hepática discreta e o índice de progressão da fibrose, calculado apenas nos pacientes com duração conhecida da infecção, foi de 0,110 para os co-infectados e de 0,130 para aqueles com infecção isolada pelo VHC, caracterizando esses pacientes como "fibrosantes lentos". Não foram encontradas diferenças estatísticas entre os grupos, apesar de menor grau de inflamação em todas as áreas analisadas, nos casos de co-infecção. Em conclusão, a co-infecção VHC / VHG não induz o surgimento de lesão hepática mais grave, favorecendo a hipótese de que o VHG não é patogênico.

As little is known about liver histology in the co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6) and HCV isolated infection (n = 16). Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.

A agregação plaquetária foi estudada em um paciente com hipercolesterolemia familiar imediatamente após aférese seletiva para lipoproteína de baixa densidade (LDL), para diminuição dos lípides plasmáticos. O tratamento reduziu os níveis plasmáticos de colesterol total, LDL-colesterol, apo B e triglicérides. A agregação plaquetária aumentada foi reduzida, imediatamente após aférese, em sangue total e em plasma rico em plaquetas, mas permanaceu sem modificações em plaquetas lavadas. Em conclusão, neste paciente, a redução dos níveis de LDL-colesterol melhorou a função plaquetária, pelo menos a muito curto prazo.

Platelet aggregation was studied in a patient with familial hypercholesterolemia immediately after aphereis selective for low-density lipoprotein (LDL), a lipid-lowering procedure.This treatment reduced plasmatic levels of total and LDL-cholesterol, apo B, and triglyceride. Increased platelet aggregation was reduced immediately after the apheresis in whole blood as well as in platelet-rich plasma. However, aggregation in washed platelets remained unchanged after LDL-apheresis. In conclusion, in this patient reduction of LDL-cholesterol improved platelet function in the very short term.