BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET) is a well established functional imaging modality for the initial staging of Hodgkin lymphoma (HL) in patients from Western Europe and North America. The reliability of FDG-PET in populations of different ethnic groups is unclear, as all investigations published to date have come from developed countries. PURPOSE: The aim of the present study was to investigate the effectiveness of FDG-PET in the initial staging of HL patients in a Brazilian population. METHODS: Eighty-two patients with newly diagnosed HL were prospectively included in the study. All patients were staged with both conventional clinical staging (CCS) methods, including computed tomography (CT) and whole-body FDG-PET methods. A standard of reference for the nodal regions and the extranodal organs was determined using all available information, including the CCS methods, FDG-PET, the diagnostic histology and the follow-up examinations. The results of the CCS were then compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher for nodal staging than that of CT (87.8% vs. 61.6%, respectively). FDG-PET was also more sensitive than CT in regard to evaluating the extranodal organs for lymphomatous involvement (96.2% vs. 40.0%, respectively). FDG-PET detected all 16 patients who were characterized by a positive bone marrow biopsy and identified an additional 4 patients with bone marrow disease. The incorporation of FDG-PET coupled with CCS in the staging procedure upstaged 20% (17/82) of the patients and downstaged 11% (9/82) of the patients. As a result of these changes in staging, 15% (13/82) of the patients would have received a different therapeutic regimen. CONCLUSIONS: The FDG-PET method is superior to CT for the detection of nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the disease was the most common result (20% of patients) brought about by the addition of PET to the staging algorithm, even in a population of patients with a high incidence of advanced disease. However, changes in stages based on FDG-PET results should be confirmed by biopsy.

Estudo retrospectivo que visa analisar a utilidade da biópsia de medula óssea (BMO) bilateral na infiltração de medula óssea (MO) por linfoma difuso de grandes células B (LDGCB). Nossos objetivos foram avaliar a incidência de infiltração unilateral de MO por LDGCB e comparar o comprimento dos fragmentos obtidos entre as amostras positivas e negativas para infiltração. Além disso, verificamos se houve diferença entre os casos com infiltração unilateral versus bilateral, correlacionando com desidrogenase láctica (DHL) e estadiamento tomográfico. Avaliamos 268 casos de LDGCB e observamos infiltração medular em 34 casos (13%). Não foi possível a avaliação de seis casos, restando 28 casos para análise. Foram revisados no total 70 fragmentos de MO sobre presença ou ausência de infiltração e comprimento. A média do número de fragmentos por casos foi 2,5; a média do comprimento dos fragmentos foi 11,01 mm (± 5,12 mm), e a média do comprimento dos fragmentos por caso foi 27,53 mm. Foi observado que em seis casos (21,4%) havia infiltração unilateral. Não foram evidenciadas diferenças nas médias do comprimento dos fragmentos em relação à presença versus ausência de infiltração 10,95 mm (± 5,1 mm) versus 11,57 mm (± 5,2 mm), p > 0,05, respectivamente. Não foram evidenciadas diferenças em 23 casos entre a comparação da infiltração medular unilateral versus bilateral com DHL e estadiamento tomográfico. Concluímos que a BMO bilateral foi superior à unilateral, pois pode aumentar a detecção de infiltração de MO em 21,4% dos casos.

This retrospective study aims to analyze the usefulness of bilateral bone marrow biopsy in bone marrow infiltration by diffuse large B-cell lymphoma (DLBCL). Our objectives were to assess the incidence of unilateral BM involvement by DLBCL and compare fragment length obtained from positive and negative samples for infiltration. Furthermore, we compared the differences between unilateral and bilateral infiltration correlating with lactic dehydrogenase (LDH) and computerized tomography (CT) staging. We evaluated 268 cases of DLBCL and observed medullary infiltration in 34 cases (13%). It was not possible to evaluate 6 out of 34 cases. 70 BM fragments were reviewed as to the presence or absence of infiltration and length. The mean number of fragments per case was 2.5; the mean BM fragment length was 11.01 mm (± 5.12 mm) and the mean BM fragment length per case was 27.53 mm. There was unilateral BM infiltration in six cases (21.4%). There were no differences in the mean fragment length as to the presence/absence of infiltration 10.95 mm (± 5.2 mm) versus 11.57 mm, p > 0.05, respectively. There were no differences in 23 cases between the comparison of unilateral medullary infiltration versus bilateral with lactic dehydrogenase and CT staging. We concluded that bilateral bone marrow biopsy was superior to unilateral because it may increase by 21.4% the detection of BM involvement by DLBCL.

O linfoma primário do sistema nervoso central (LPSNC) é um linfoma extralinfonodal que, ao diagnóstico, encontra-se restrito ao parênquima cerebral, às meninges e/ou cordão espinhal e/ou olhos. Sua incidência triplicou nas últimas três décadas para 0,4 casos por 100.000 habitantes, representando 4% dos tumores do sistema nervoso central (SNC). Embora pacientes infectados pelo HIV tenham 3.600 vezes maior risco para o desenvolvimento do LPSNC, a incidência não aumentou apenas neste grupo de pessoas. Dados sugerem reduções da incidência de LPSNC em pacientes infectados após a introdução de drogas anti-retrovirais. Cerca de 90% dos casos de LPSNC são classificados como linfoma difuso de grandes células B, 10% têm envolvimento ocular e 10% são HIV positivos. A apresentação clínica depende da localização tumoral, prevalecendo os sintomas neurológicos em detrimento aos sistêmicos. Os exames de tomografia computadorizada (TC) e ressonância nuclear magnética (RNM) são essenciais para o diagnóstico, porém o exame confirmatório deve ser o anatomopatológico. O estadiamento deve ser feito com exames de imagem e biópsia de medula óssea (BMO) bilateral. Os principais fatores de mau prognóstico são: performance status do paciente acima de 1, idade superior a 60 anos, DHL elevada, hiperproteinorraquia e acometimento de área cerebral não hemisférica. Alguns fatores de prognóstico biológicos também podem influenciar na sobrevida, a exemplo da expressão de Bcl-6, que confere melhor prognóstico. O tratamento de escolha é a combinação de quimioterapia contendo altas doses de metotrexate e radioterapia (RDT). Devido às altas taxas de neurotoxicidade associada à RDT, seu uso tem ficado mais restrito aos pacientes idosos, e os recidivados ou refratários.

Primary Central Nervous System lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma in the brain, leptomeninges, spinal cord or eyes. The incidence of PCNSL increased approximately three-fold in the last decades. Nowadays, it represents 0.4 case per 100,000 people and accounts for 4% of all primary brain tumors. Although individuals infected with HIV have a 3,600-fold increased risk of developing PCNSL compared with the general population, the incidence has not increased only in AIDS group. Recent data suggest that the incidence of PCNSL declined in the AIDS group after the introduction of anti-retroviral drugs. Around 90% of PCNSL cases are classified as diffuse large B-cell lymphoma, 10% involve the eyes and 10% of patients are HIV positive. The clinical presentation depends on the location of the tumor with neurological rather than systemic symptoms. Computed tomography (CT) and magnetic resonance imaging (RMI) are essential in diagnosis, however the gold standard is tumor biopsy. Staging should be made with imaging and bilateral biopsy of bone marrow. The main poor prognosic parameters are performance status greater than 1, age older than 60 years, elevated DHL, high liquor protein concentration and tumor located within the deep regions of the brain. BCL-6 expression identified in the tumor confers a better prognosis. Currently, a combined therapy with high doses of methotrexate and whole-brain radiotherapy is the therapy of choice. Nowever, whole-brain radiotherapy should be carefully analyzed because neurotoxity is a frequent problem in the elderly and in relapsed and refractory patients.

CONTEXTO E OBJETIVO: A policitemia vera (PV) é uma doença mieloproliferativa crônica, caracterizada pela proliferação de precursores hematopoéticos, principalmente da série eritróide. Poucos dados são disponíveis sobre pacientes brasileiros portadores desta doença. O objetivo do presente estudo é analisar as características de pacientes portadores de PV ao diagnóstico e a sua evolução clínica a longo prazo. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo unicêntrico, realizado no Serviço de Hematologia da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foram elegíveis para este estudo os pacientes com PV diagnosticados de acordo com os critérios estabelecidos pela Organização Mundial da Saúde. Foram avaliadas as características demográficas e clínicas ao diagnóstico, as complicações trombóticas, a transformação para leucemia aguda e mielofibrose e a sobrevida. RESULTADOS: Foram avaliados 66 pacientes; 36 (54,5%) eram do sexo feminino, com uma mediana de idade ao diagnóstico de 61 anos. As medianas da concentração de hemoglobina e da plaquetometria ao diagnóstico foram de 18,8 mg/dl e 593.000/mm³, respectivamente. 58 (88,0%) foram tratados com hidroxiuréia associada ou não à flebotomia. Em uma mediana de acompanhamento de 77 meses, 22 (33,3%) pacientes apresentaram eventos trombóticos, predominantemente arteriais. A incidência de leucemia e mielofibrose foi de 0,42/100 pacientes-ano e 1,06/100 pacientes-ano, respectivamente. A mediana de sobrevida global não foi atingida, a taxa de sobrevida em sete anos foi de 77,8%. CONCLUSÃO: Os portadores de PV em nosso serviço apresentaram longa sobrevida. Os eventos trombóticos arteriais foram a principal complicação da população estudada.

CONTEXT AND OBJECTIVE: Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by predominant proliferation of erythroid precursors. Few data are available concerning Brazilian patients with this condition. The aim of this study was to describe clinical and demographic characteristics of PV patients at diagnosis and analyze their long-term outcomes. DESIGN AND SETTING: Retrospective study at the Division of Hematology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo. METHODS: All consecutive patients with PV diagnosed according to World Health Organization criteria were eligible for this study. Clinical and demographic characteristics, thrombotic events, transformation to acute leukemia, myelofibrosis and survival were evaluated. RESULTS: Sixty-six patients were evaluated. Thirty-six (54.5%) were females, with a median age at diagnosis of 61 years. At diagnosis, the median hemoglobin concentration was 18.8 mg/dl and the median platelet count was 593,000/mm³. Fifty-eight patients (88.0%) were treated with hydroxyurea with or without phlebotomy. During a median follow-up of 77 months, 22 patients (33.3%) had new thrombotic events, mainly of arterial type. The overall incidence of leukemia and myelofibrosis was 0.42% per patient-year and 1.06% per patient-year, respectively. Median overall survival was not reached and the seven-year survival rate was 77.8%. CONCLUSION: The PV patients described here had long survival and arterial thrombotic events were the most important and common complication among this population.

Patients with Hodgkin's lymphoma relapsed after or refractory to multiple therapies (rHL) have a dismal prognosis. Monotherapy with gemcitabine can promote an overall response rate of about 40% in these patients and its association with alkylating agents can provide better results. We retrospectively evaluated 17 rHL cases. All were treated with the combination of gemcitabine (1.0 g/m²; D1 and D8) and ifosfamide (1.0 g/m²; D1 to D5) in a 21-day cycle. Treatment response was evaluated according to the Cotswolds criteria. Toxicity was evaluated according to WHO criteria. The median age of all patients was 34 years (18-53). Nine of them (53%) were men and eight (47%) had Stage III/IV. The median number of previous treatments was 2 (2-3); two patients had already been treated with autologous stem cell transplant. Overall response rate to the combined regimen was 62.5% (95% CI = 38.8% - 86.2%) and the median progression-free survival was 15 months (95% CI = 4 - 24 months). Fifty-six cycles were evaluated for toxicity. The most frequent toxicities observed by cycle were: hepatic Grade I/II in 48.2% of the cycles and Grade III/IV in 1.8%; anemia Grade I/II in 45%; neutropenia Grade I/II in 36% and Grade III/IV 16%. Grade III/IV renal toxicity on any degree of haematuria were not observed. Combined therapy with Gemcitabine and Ifosfamide promoted responses in more than half of the evaluated patients with an acceptable toxicity profile.

OBJETIVO: O estudo metabólico com 18F-fluorodeoxiglicose é uma ferramenta útil para o manejo de portadores de linfoma de Hodgkin, tanto como método auxiliar no estadiamento da doença, quanto na avaliação de massas suspeitas encontradas após tratamento. O objetivo deste estudo foi investigar o valor do estudo com 18F-fluorodeoxiglicose em gama câmara híbrida no estadiamento e na detecção de tumor residual em pacientes com linfoma de Hodgkin. MÉTODOS: Trinta e oito pacientes foram incluídos neste estudo retrospectivo, 18 foram avaliados com o estudo metabólico durante o estadiamento (Grupo 1), sendo os resultados do estudo comparados com os obtidos com o estadiamento convencional, que incluiu tomografia e biópsia de medula óssea. Os 20 pacientes restantes realizaram o estudo metabólico devido à presença de massa residual ou de nova lesão suspeita (Grupo 2). RESULTADOS: O estudo metabólico aumentou o estádio de cinco (27%) dos pacientes do Grupo 1 e pôde detectar mais lesões que os métodos convencionais de estadiamento (45 lesões detectadas com 18F-fluorodeoxiglicose versus 33 lesões métodos convencionais). Nos 20 pacientes do Grupo 2, 11 foram 18F-fluorodeoxiglicose positivos e tumor viável foi confirmado em 9 pacientes. Nos 9 pacientes com estudo metabólico negativo, a probabilidade de recidiva em um ano foi de 11.8%. A sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e a acurácia do estudo metabólico foram de 90%, 80%, 82%, 89% e 85% respectivamente. CONCLUSÕES: O estudo com 18F-fluorodeoxiglicose apresentou melhor acurácia que os métodos convencionais de estadiamento do Linfoma de Hodgkin e foi útil para o diagnóstico não-invasivo de lesões suspeitas.

OBJECTIVE: The metabolic test using 18F-fluorodeoxyglucose is a useful tool for the management of patients with Hodgkin lymphoma, either for staging purposes or for the evaluation of suspicious masses that can frequently occur after treatment. The aim of the present study was to investigate the value of the 18F-fluorodeoxyglucose test performed with a dual-head coincident gamma camera (CGC-PET with fluorodeoxyglucose) for the staging and the detection of residual tumor of patients with Hodgkin lymphoma. METHODS: Thirty-eight consecutive patients were included in this retrospective study; the metabolic test comprising CGC-PET with FDG was done in 18 patients for staging work-up (Group 1), and the results were compared to conventional clinical staging procedures that included computed tomography scans and bone marrow biopsy. The remaining 20 patients were evaluated with CGC-PET with fluorodeoxyglucose due to the presence of residual masses or a new lesion (Group 2). RESULTS: The 18F-Fluorodeoxyglucose metabolic test, CGC-PET with fluorodeoxyglucose, upstaged 5 (27%) of the Group 1 patients and detected more lesions (45) than conventional methods of staging (33). Of the 20 patients in Group 2, 11 had positive18F-fluorodeoxyglucosetests, and a viable tumor was confirmed in 9 patients. Regarding the 9 patients with negative fluorodeoxyglucose metabolic tests, the 1-year probability of recurrence was 11.8%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CGC-PET with fluorodeoxyglucose test were 90%, 80%, 82%, 89%, and 85% respectively. CONCLUSIONS: The metabolic test comprising CGC-PET with fluorodeoxyglucose had a higher diagnostic accuracy than conventional methods in the staging of Hodgkin lymphoma and thus is a valuable noninvasive tool for the diagnosis of suspicious lesions.

O linfoma difuso de grandes células B (LDGCB) é uma entidade clínico-patológica heterogênea que corresponde de 30% a 35% dos casos de linfoma não-Hodgkin (LNH). É considerado como agressivo porque a sobrevida é curta na ausência de tratamento adequado. Desde 1993 o tratamento deste linfoma passou a ser direcionado pelo índice internacional de prognóstico (IPI) validado em vários estudos. Entretanto, diante das diferentes respostas à mesma terapêutica para pacientes de mesmo IPI houve necessidade de se instituírem novos marcadores de prognóstico para pacientes com LDGCB. Com os avanços do conhecimento biológico destes linfomas, outras variáveis começam a ser utilizadas na estratificação de risco destes linfomas. Nesta revisão abordamos os principais marcadores biológicos utilizados como fatores de prognóstico para o tratamento de pacientes com LDGCB.

Diffuse large B-cell lymphoma is a heterogeneous clinical pathological entity which accounts for about 30% to 35% of all non-Hodgkin's lymphoma cases. It is considered to be aggressive due to the patient's short survival time when incorrect treatment is provided. Since 1993, treatment has been carried out according to IPI, which has been validated in several studies. However, since there are different responses from patients with the same IPI submitted to similar therapies, new prognostic markers are needed for these patients. As the biological nature of such lymphomas is becoming better known, other variables are starting to be used in order to stratify risk. In this review we will approach the key biological markers used as prognostic factors to treat diffuse Large B-Cell Lymphoma patients.

INTRODUÇÃO: A esclerose nodular (EN), do tipo histológico freqüente do linfoma de Hodgkin (LH), apresenta grande variabilidade em sua composição celular. Na década de 80, pesquisadores do British National Lymphoma Investigation (BNLI) propuseram uma subclassificação histológica do LH EN. Eles identificaram dois graus histológicos - o LH EN grau I (LH EN I) e o LH EN grau II (LH EN II) - e demonstraram que os portadores de LH EN II apresentavam menor sobrevida em comparação aos portadores de LH EN I. Outros estudos, entretanto, não reproduziram esses achados. OBJETIVO: Avaliar o significado prognóstico da graduação histológica proposta pelo BNLI. MATERIAIS E MÉTODOS: Estudo retrospectivo que incluiu 69 casos de LH EN. Mais de 90% dos casos foram tratados com terapia combinada ou quimioterapia exclusiva, não havendo diferença no tipo de tratamento oferecido a depender do grau histológico. RESULTADOS: Trinta e cinco casos (51%) foram classificados com EN I e 34 (49%) como EN II. Não observamos diferenças na distribuição de outros fatores prognósticos entre os portadores dos dois graus. Remissão completa após o tratamento inicial foi obtida em 85,7% dos casos de EN I e em 82,4% dos casos de EN II (p = 0,75). A probabilidade estimada de sobrevida global em cinco anos foi de 67% para EN I e de 83,5% para EN II (p = 0,13) e a taxa de sobrevida livre de doença em cinco anos foi de 85,2% versus 87%, respectivamente (p = 0,72). CONCLUSÃO: Nesta população de pacientes uniformemente tratados a graduação histológica BNLI não esteve associada com o prognóstico do LH EN.

BACKGROUND: Nodular sclerosis (NS), a frequent histological subtype of Hodgkin’s lymphoma (HL), presents great variability in its cellular composition. In the 80's, researchers of the British National Lymphoma Investigation (BNLI) proposed a histological-based subclassification for NS HL. They identified two histological grades - NS HL grade I (NS HL I) and NS HL grade II (NS HL II) - and reported that NS II patients had a lower survival rate in comparison with NS I patients. Others studies, however, did not reproduce these findings. OBJECTIVE: Evaluate the prognostic significance of the BNLI grading system. MATERIAL AND METHOD: We retrospectively studied 69 NS HL patients. More than 90% of the included cases were treated with combined modality therapy or exclusive chemotherapy, the treatment type was not different for NS I and NS II patients. RESULTS: Thirty-five cases (51%) were classified as NS I and 34 (49%) as NS II. We did not observe significant differences in the distribution of other prognostic factors between the two NS grades. The complete remission rate after initial therapy was 85.7% in the NS I group and 82.4% in the NS II group (p = 0.75). The predicted 5-year overall survival rate was 67% in the NS I patients and 83.5% in the NS II patients (p = 0.13). The predicted 5-year disease free survival rate for NSI and NSII patients was 85.2% and 87%, respectively (p = 0.72). CONCLUSION: The histological BNLI grading system was not associated with the prognosis of this uniformly treated NS LH population.

OBJETIVO: Infecção é a principal complicação relacionada ao uso de cateteres venosos de longa permanência em pacientes oncológicos e sua incidência pode variar a depender do tipo de cateter utilizado. O objetivo deste estudo foi comparar a freqüência e risco de infecção entre dois tipos de dispositivos de longa permanência. MÉTODOS: Estudo retrospectivo com 96 pacientes onco-hematológicos portadores de cateteres parcialmente implantáveis (n=55) ou totalmente implantáveis (n=42). Dados demográficos e cuidados com o dispositivo foram similares entre os dois grupos. A comparação entre os dispositivos foi realizada através da avaliação da incidência de infecção e da sobrevida livre de infecção. RESULTADOS: Em uma mediana de acompanhamento de 210 dias, a incidência de infecção relacionada ao cateter foi de 0,2102/100 cateter-dias para os dispositivos parcialmente implantáveis e de 0,0045/100 cateter-dias para os totalmente implantáveis, com uma razão de incidência de 46,7 (IC 95% = 6,2 a 348,8). A taxa de sobrevida livre de primeira infecção em um ano foi de 45% versus 97% e a taxa de sobrevida livre de retirada por infecção foi de 42% versus 97%, respectivamente para cateter parcialmente ou totalmente implantável (p<0,001 para ambas comparações). Conclusão: No presente estudo, o risco de infecção foi menor nos dispositivos totalmente implantáveis do que nos parcialmente implantáveis.

PURPOSE: Infection is the leading complication of long-term central venous catheters, and its incidence may vary according to catheter type. The objective of this study was to compare the frequency and probability of infection between two types of long-term intravenous devices. METHODS: Retrospective study in 96 onco-hematology patients with partially implanted catheters (n = 55) or completely implanted ones (n = 42). Demographic data and catheter care were similar in both groups. Infection incidence and infection-free survival were used for the comparison of the two devices. RESULTS: In a median follow-up time of 210 days, the catheter-related infection incidence was 0.2102/100 catheter-days for the partially implanted devices and 0.0045/100 catheter-days for the completely implanted devices; the infection incidence rate was 46.7 (CI 95% = 6.2 to 348.8). The 1-year first infection-free survival ratio was 45% versus 97%, and the 1-year removal due to infection-free survival ratio was 42% versus 97% for partially and totally implanted catheters, respectively (P <.001 for both comparisons). CONCLUSION: In the present study, the infection risk was lower in completely implanted devices than in partially implanted ones.