OBJECTIVES: The outcomes of refractory and relapsed acute myeloid leukemia (AML) patients in developing countries are underreported, even though the similar classic regimens are widely used. METHODS: We conducted a retrospective comparison of “MEC” (mitoxantrone, etoposide, and cytarabine) and “FLAG-IDA” (fludarabine, cytarabine, idarubicin, and filgrastim) in adults with first relapse or refractory AML. RESULTS: In total, 60 patients were included, of which 28 patients received MEC and 32 received FLAG-IDA. A complete response (CR) rate of 48.3% was observed. Of the included patients, 16 (27%) died before undergoing bone marrow assessment. No statiscally significant difference in CR rate was found between the two protocols (p=0.447). The median survival in the total cohort was 4 months, with a 3-year overall survival (OS) rate of 9.7%. In a multivariable model including age, fms-like tyrosine kinase 3 (FLT3) status, and stem-cell transplantation (SCT), only the last two indicators remained significant: FLT3-ITD mutation (hazard ratio [HR]=4.6, p<0.001) and SCT (HR=0.43, p=0.01). CONCLUSION: In our analysis, there were no significant differences between the chosen regimens. High rates of early toxicity were found, emphasizing the role of supportive care and judicious selection of patients who are eligible for intensive salvage therapy in this setting. The FLT3-ITD mutation and SCT remained significant factors for survival in our study, in line with the results of previous studies.

ABSTRACT Objective: To investigate, in a large prospective multicenter study, whether 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography is sufficiently accurate to identify clinically important bone marrow involvement by Hodgkin's lymphoma to replace routine bone marrow biopsy in a developing tropical country. Methods: Patients newly diagnosed with Hodgkin's lymphoma were recruited from six cancer centers in Brazil. All were staged by the results of positron emission tomography/computed tomography that were centrally reviewed and by iliac crest bone marrow biopsy. Patients were classified as having marrow disease if they had lymphoma identified by marrow biopsy histology or had focal 2-[18F]-fluoro-2-deoxy-D-glucose marrow uptake that resolved following chemotherapy. Results: A total of 246 participants were recruited from six different centers and 62 (25.2%) were judged to have Hodgkin's lymphoma in the bone marrow. Positron emission tomography and biopsies were concordant in 206 patients (83%). Positron emission tomography correctly identified marrow disease in 59/62 patients (95.1%) and marrow biopsy in 25/62 patients (40.3%). In 22/62 (35.4%) patients, the two techniques were concordant in the diagnosis of marrow involvement. Of the forty discordant results, positron emission tomography found bone marrow involvement in 37 patients, upstaging 22 to stage IV and having an impact on therapeutic decision in nine cases given their reallocation from early to advanced stage. Three false negative positron emission tomography results were obtained with bone marrow biopsy giving positive findings. All three cases were classified as stage IV regardless of bone marrow findings implying no modification in the clinical management. The sensitivity, specificity and accuracy of positron emission tomography for detecting bone marrow disease were 95%, 100% and 98% and for bone marrow biopsy they were 40%, 100% and 84%, respectively. Conclusion: We conclude that positron emission tomography can replace marrow biopsy in Brazilian patients with Hodgkin's lymphoma without compromising clinical management.

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.

O linfoma de Hodgkin clássico (LHC) é uma neoplasia com distúrbio na produção de citocinas. Estudos demonstram que o padrão anormal das citocinas no linfonodo acometido pela lesão contribui não somente com a proliferação das células malignas H-RS, como também com o característico infiltrado hiper-reativo que compõe o tecido no LHC. Esta disfunção pode ser observada tanto no quadro clínico dos pacientes, como nas características histopatológicas: sintomas B, deficiência na resposta imune celular, bandas de colágeno e eosinofilia. As concentrações séricas das citocinas Th1 (IL-2, TNF, INF-γ) e Th2 (IL-4, IL-5, IL-10) foram estudadas em 45 pacientes com LHC, ao diagnóstico, e em 34 doadores saudáveis, por citometria de fluxo (CBA - cytometric beads array). Houve aumento das concentrações das citocinas TNF (p<0,01), INF-γ (p<0,01), IL-4 (p=0,01), IL-5 (p<0,01) e IL-10 (p<0,01) dos pacientes quando comparados com o grupo controle. Não foi evidenciada diferença em relação a IL-2. Ao correlacionarmos as concentrações das citocinas Th1/Th2 com as variáveis clínico-laboratoriais dos pacientes, observou-se que níveis elevados da IL-10 (Th2) estão correlacionados com as variáveis que implicam em pior prognóstico: estádios III/IV (p=0,01), presença de sintomas B (p=0,04), hemoglobina < 10,5g/dL (p=0+,01), linfócitos <600 mm³ (p=0,01) e, de acordo com o IPI, os pacientes de alto risco (p=0,01). Por outro lado, níveis séricos elevados da IL-2 (Th1) foram encontrados em estádio I/II, quando comparados com III/IV (p=0,03), o que indica que a IL-2 diminui com a progressão da doença. Os resultados sugerem que a IL-10 possa estar regulando negativamente a resposta imune citotóxica (Th1) pela inibição da IL-2. Há uma possível associação entre progressão da doença e níveis elevados da IL-10. Esse estudo evidenciou que a utilização do CBA é factível na detecção das citocinas, e que as alterações encontradas podem estar envolvidas na biologia do LHC.

Classical Hodgkin lymphoma (CHL) is a malignancy with an abnormal or unbalanced secretion/production of cytokines, which might support the growth of H-RS cells, their surrounding reactive bystander cells and may be responsible for the typical clinical and histopathologic features of CHL: systemic B symptoms, an apparent defect in cell-mediated immune response, tumor fibrosis and eosinophilic infiltrate. Serum concentrations of IL-2, IL-4, IL5, IL-10, TNF and IFN-γ (Th1/Th2) were measured in 45 patients at diagnosis of classical Hodgkin lymphoma and in 34 healthy controls by cytometric beads array (CBA). Levels of TNF (p<0.01), INF-γ(p<0.01), IL-4 (p=0.01), IL-5 (p<0.01) e IL-10 (p<0.01) were significantly higher in patients compared to the control group. No difference was observed for IL-2 between the two groups. On correlating Th1/Th2 cytokine concentrations with clinical risk factors, elevated IL-10 (Th2) levels are associated with variables that suggest worse prognoses including III/IV stage (p=0.01), B-symptoms (p=0.04), hemoglobin < 10.5g/dL (p=0.01), lymphocytes < 600/mm³ (p=0.01) and according to the seven-factored international prognostic score (IPI), a subset of patients with a particularly high risk of failure (p=0.01). Furthermore, the serum levels of IL-2 (Th1) were significantly higher in a group of I/II stage patients compared to III/IV patients (p=0.03) which implies that, the levels of IL-2 might decrease with disease progression. The elevated IL-10 levels in a subset of patients with poor clinical risk factors might down regulate a Th1 immune response by inhibiting IL-2 production causing survival disadvantage by suppression of the cytotoxic immune response against the tumor. This suggests an association between progression of CHL and higher levels of the IL-10 cytokine. This study showed that measurement of serum cytokines using the CBA methodology is highly reproducible, and that changes in concentrations seem to be involved in the biology of this diseas.

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.

O linfoma de Hodgkin (LH) é uma neoplasia do tecido linfóide de excelente prognóstico, porém, aproximadamente 15% dos pacientes em estádios precoces e 35% dos em estádios avançados progridem após o tratamento inicial. O transplante autólogo de medula óssea ou de células-tronco periféricas (ATMO) é o tratamento de escolha nesses casos. Nosso estudo tem como objetivo avaliar o tipo de tratamento utilizado, a taxa de resposta e a sobrevida de pacientes recidivados ou refratários ao ATMO. De 38 pacientes com LH submetidos a ATMO entre abril de 1996 e novembro de 2005, foram avaliados 17 que apresentaram recidiva/refratariedade ao ATMO. Nesses casos, o tratamento de resgate foi individualizado, a depender das condições clínicas de cada um, sendo constituído usualmente de drogas citotóxicas não utilizadas previamente. Após o ATMO, dez (59%) dos 17 pacientes obtiveram remissão completa, um (6%) remissão parcial e seis (35%) foram refratários. Em 14 dos 17 pacientes foi instituída quimioterapia de resgate com diversos esquemas no momento da recidiva/refratariedade após ATMO; um paciente foi tratado com radioterapia exclusiva e dois foram a óbito antes de qualquer terapia. Observamos uma taxa de resposta global de 57,4% (IC95%: 23,2 - 90,7%). A mediana da sobrevida livre de progressão foi de 19 meses e a mediana de sobrevida global foi de 32 meses. Apesar do LH recidivado/refratário ao ATMO não ser curável com os quimioterápicos atualmente disponíveis, os pacientes apresentaram longa sobrevida, com freqüentes exacerbações da doença.

Hodgkin's lymphoma (HL) is a lymphoid malignancy with excellent prognosis, however nearly 15% of the patients in early stages and 35% in advanced stages have progressive disease after initial treatment. Autologous bone marrow or hematopoietic stem cell transplantation (ABMT) are the treatments of choice in these cases. This report presents the therapeutic approach and the outcome of HL patients who experience relapse after or are refractory to ABMT. Of 38 patients with LH who underwent ABMT between April 1996 and November 2005, 17 presented with relapsed/refractory disease and were included in this analysis. In these cases, the choice of rescue therapy varied upon the clinical conditions of each patient and was based on previously unused chemotherapy agents. After ABMT, 10 (59%) of the 17 patients were in complete remission, one (6%) in partial remission and six (35%) were refractory. Fourteen of the 17 patients received different schemes of rescue therapy at the time of ABMT failure, one patient was treated exclusively with radiotherapy and two died before any treatment. We observed an overall response rate of 57.4% (95% CI: 23.2 - 90.7%). The median progression-free survival was 19 months and the median overall survival was 32 months. Despite ABTM, relapsed/refractory LH can not be cured with currently available chemotherapeutic agents, the patients had long survival times with frequent exacerbations of the diseas.

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.

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.