Abstract: Background: Diseases caused by melanized fungi include mycetoma, chromoblastomycosis and phaeohyphomycosis. This broad clinical spectrum depends on the dynamic interactions between etiologic agent and host. The immune status of the host influences on the development of the disease, as, an exemple. phaeohyphomicosis is more frequently observed in immunocompromised patients. Objectives: Examine the histological inflammatory response induced by Fonsecaea pedrosoi in several different strains of mice (BALB/c, C57BL/6, Nude and SCID, and reconstituted Nude). Methods: Fonsecaea pedrosoi was cultivated on agar gel and a fragment of this gel was implanted subcutaneously in the abdominal region of female adult mice. After infection has been obtained, tissue fragment was studied histopathologically. Results: There were significant changes across the strains, with the nodular lesion more persistent in Nude and SCID mice, whereas in immunocompetent mice the lesion progressed to ulceration and healing. The histopathological analysis showed a significant acute inflammatory reaction which consisted mainly of neutrophils in the initial phase that was subsequently followed by a tuberculoid type granuloma in immunocompetent mice. Study limitations: There is no a suitable animal model for chromoblastomycosis. Conclusions: The neutrophilic infiltration had an important role in the containment of infection to prevent fungal spreading, including in immunodeficient mice. The fungal elimination was dependent on T lymphocytes. The re-exposure of C57BL/6 mice to Fonsecaea pedrosoi caused a delay in resolving the infection, and appearance of muriform cells, which may indicate that re-exposure to fungi, might lead to chronicity of infection.

Objective: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-β1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. Methods: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-β1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. Results: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-β1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value < 0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-β1 expression and microvascular density (r = 0.45; p-value < 0.0009) and between degree of microvascular density and fibrosis grade (r = 0.80; p-value < 0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. Conclusion: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-β is differentially expressed only in the prefibrotic stage.

BACKGROUND: The detection of molecular and cytogenetic alterations is important for the diagnosis, prognosis and classification of myeloproliferative neoplasms. OBJECTIVE: The aim of this study was to detect the following mutations: JAK2 V617F, JAK2 exon 12 and MPL W515K/L, besides chromosomal abnormalities. Furthermore, molecular and cytogenetic alterations were correlated with the leukocyte and platelet counts, hemoglobin levels and age in all patients and with the degree of fibrosis in primary myelofibrosis cases. METHODS: Twenty cases of polycythemia vera, 17 of essential thrombocythemia and 21 of primary myelofibrosis were selected in the Hematology Department of the Universidade Federal de São Paulo (UNIFESP) between February 2008 and December 2009. The JAK2 V617F, JAK2 exon 12 mutations, MPL W515K and MPL W515L mutations were investigated by real-time PCR and direct sequencing. G-band karyotyping and fluorescence in situ hybridization were used to detect chromosomal abnormalities. RESULTS: Chromosomal abnormalities were observed only in polycythemia vera (11.8%) and primary myelofibrosis cases (17.6%), without correlation to clinical data. Chromosomal abnormalities were not detected by fluorescence in situ hybridization. The JAK2 V617F mutation was observed in polycythemia vera (90%), primary myelofibrosis (42.8%) and essential thrombocythemia (47%). Patients with JAK2 V617F-negative polycythemia vera had lower platelet and leukocyte counts compared to V617F-positive polycythemia vera (p-value = 0.0001 and p-value = 0.023, respectively). JAK2 V617F-positive and MPL W515L-positive primary myelofibrosis cases had a higher degree of fibrosis than V617F-negative cases (p-value = 0.022). JAK2 exon 12 mutations were not detected in polycythemia vera patients. The MPL W515L mutation was observed in one case of primary myelofibrosis and in one of essential thrombocythemia. The MPL W515K mutation was not found in patients with essential thrombocythemia or primary myelofibrosis. The MPL W515L-positive patient with primary myelofibrosis had more severe anemia than other patients with primary myelofibrosis. CONCLUSIONS: This study demonstrates that karyotyping for JAK2 and MPL mutations is useful in the diagnosis of myeloproliferative neoplasms. The precise pathogenetic contribution of these alterations is still unclear. However, this study adds more information about the pathophysiology of polycythemia vera, essential thrombocythemia and primary myelofibrosis.

OBJETIVO: Avaliar, no coração, por imuno-histoquímica, a localização das proteínas TGFbeta1 latente e TGFbeta1 ativa, se ocorre ativação radioinduzida da proteína TGFbeta1 latente, e a distribuição das fibras colágenas em diversos períodos de tempo após irradiação. MATERIAIS E MÉTODOS: Trinta e dois camundongos isogênicos (C57BL) foram divididos em dois grupos: GI (não irradiado), com 12 animais, e GII (irradiado), com 20 animais. Os animais do GII receberam radiação gama (telecobaltoterapia, 60Co, com rendimento de 0,97 Gy/min., dose única de 7 Gy em corpo inteiro). Os camundongos dos grupos I e II foram sacrificados por estiramento cervical nos períodos de 1, 14, 30 e 90 dias após irradiação. RESULTADOS: Os corações irradiados apresentaram: 1) alterações nucleares e diminuição das estriações das células musculares cardíacas; 2) aumento significante da deposição de fibras colágenas aos 90 dias depois da irradiação; 3) ativação da proteína TGFbeta1 latente em cardiomiócitos e células do conjuntivo depois da irradiação. CONCLUSÃO: Nossos resultados mostram a importância da proteína TGFbeta1 no processo de fibrose cardíaca radioinduzida e sugerem que células do parênquima (cardiomiócitos) e do conjuntivo podem participar deste mecanismo atuando como fontes da proteína TGFbeta1 ativa.

OBJECTIVE: To assess the latent and active TGFbeta1 localization in the heart, to evaluate whether or not radiation induces latent TGFbeta1 activation, and to study the distribution of collagen fibers in the irradiated heart. MATERIALS AND METHODS: Thirty-two C57BL mice were randomly assigned in two groups: GI (non irradiated animals) and GII (irradiated animals). The mice from GII received a single whole-body radiation dose of 7Gy, using a 60Co source at a dose rate of 0.97 Gy/min. The animals were sacrificed by cervical dislocation at 1, 14, 30 and 90 days after irradiation. RESULTS: The irradiated hearts showed: 1) nuclear changes and muscle cells with decreased striations; 2) significant increase in the collagen deposition 90 days after irradiation; 3) latent TGFbeta1 activation in the cardiomyocytes and connective tissue cells after irradiation. CONCLUSION: Our results show the importance of TGFbeta1 protein in the process of radiation-induced heart fibrosis and suggest that cardiomyocytes and connective cells may play a role in this mechanism acting as cellular sources of active TGFbeta1.

RACIONAL: Laminina sérica tem sido correlacionada com a hipertensão portal e a capilarização dos sinusóides na doença hepática crônica. Pouco é conhecido sobre sua dinâmica nas doenças hepáticas. OBJETIVO: Estudar os níveis séricos de laminina e correlacioná-los com graus de fibrose hepática e hipertensão portal em ratos tratados com tetracloreto de carbono. MATERIAL E MÉTODO: Quarenta e nove ratos albinos Wistar foram mantidos como controles (n = 16) ou tratados com solução de tetracloreto de carbono a 8% (n = 23). Entre a 6ª e 16ª semana de experimento animais foram sacrificados após cateterização da veia porta e medida da pressão portal. Fragmentos de fígado foram fixados em formol para microscopia óptica. A fibrose hepática foi classificada em perivenular, septal incompleta e completa e cirrose. Concentração de laminina circulante foi determinada pela técnica de ensaio imunoenzimático com anticorpo desenvolvido a partir de laminina isolada de tumor Engelbreth-Holm-Swarm e purificado em coluna de afinidade. RESULTADOS: A pressão portal correlacionou-se com grau de fibrose hepática (r = 0,82; n = 45) e seus níveis nos grupos fibrose septal (10,8 ± 1,2 cm H2O) e cirrose (13,6 + 3,1 cm H2O) foram estatisticamente superiores aos observados no grupo-controle (7,9 + 1,5 cmH2O) e no grupo com fibrose perivenular (9,1 + 0,8 cmH2O). A concentração de laminina no sangue periférico dos cirróticos (40,0 + 18,7 µg/dL) foi significativamente superior aos grupos-controle (13,8 + 12,1 µg/dL), fibrose perivenular (19,1 + 15,5) e fibrose septal (22,2 + 27,0 µg/dL). Laminina circulante correlacionou-se de maneira significativa com o grau de fibrose hepática (r = 0,59; n = 49) e com os níveis de pressão portal (r = 0,29; n = 45). CONCLUSÕES: Na intoxicação crônica experimental pelo tetracloreto de carbono, níveis circulantes de laminina correlacionam-se mais com o grau de fibrose hepática do que com os níveis de hipertensão portal.

BACKGROUND: Serum laminin has been correlated with portal hypertension and sinusoid capillarization in chronic liver diseases. Little is known about its dynamics in liver diseases. AIM: To investigate the levels of serum laminin in experimental cirrhosis induced by carbon tetrachloride, as well as to correlate its level with the degree of hepatic fibrosis and portal hypertension. MATERIAL AND METHODS: Forty-nine albino Wistar rats were studied. Twenty-three were treated with carbon tetrachloride solution at 8% and 16 were kept as controls. Between the 6th and 16th weeks, all animals were sacrificed, submitted to measurement of portal pressure and blood sampling of the femoral veins. Liver fragments were fixed for light microscopic studies. Hepatic fibrosis was classified as perivenular fibrosis, complete and incomplete septal fibrosis and cirrhosis. Determination of laminin concentration was performed by ELISA with an antibody against laminin isolated from Engelbreth-Holm-Swarm tumor. RESULTS: The portal pressure was correlated with the degree of hepatic fibrosis (rs = 0.82; n = 45). Its levels in septal fibrosis (10.8 ± 1.2 cm H(2)0) and cirrhosis (13.6 ± 3.1 cm H(2)0) were statistically higher when compared to control (7.9 ± 1.5 cm H20) and perivenular fibrosis (9.1 ± 0.8 cm H(2)0) groups. Peripheral blood laminin concentration in cirrhosis (40.0 ± 18.7 mg/dL) was significantly higher when compared to control (13.8 ± 12.1 mg/dL), perivenular fibrosis (19.1 ± 15.5 mg/dL) and septal fibrosis (22.2 ± 27.0 mg/dL) groups. The circulating laminin was correlated to the degree of hepatic fibrosis (rs = 0.59; n = 49) and to portal pressure (r = 0.29; n = 45). CONCLUSIONS: In the chronic carbon tetrachloride intoxication, laminin levels are better correlated with the development of hepatic fibrosis than with portal hypertension.

Contexto: A fibrose de medula óssea é encontrada em algumas doenças hematológicas clonais, incluindo síndromes mieloproliferativas, leucemias agudas e síndromes mielodisplásicas. Nas síndromes mielodisplásicas, uma nova entidade clinicopatológica com acentuado aumento das fibras de reticulina tem sido sugerida, e o termo "síndrome mielodisplásica hiperfibrótica" é usado para sua definição. A biópsia de medula óssea mostra aumento das fibras de reticulina e hiperplasia megacariocítica com displasia. O diagnóstico diferencial com mielofibrose primária é difícil, e casos híbridos podem ocorrer. Pacientes com síndromes mielodisplásicas hiperfibróticas que respondem à terapia com corticosteróide têm sido descritos. Na maioria dos casos a remissão é apenas hematológica, mas resolução da fibrose de medula óssea já ocorreu em um paciente. Planejamento: Relato de caso. Relato: Paciente do sexo masculino, 62 anos de idade, apresentou-se, em junho de 1995, com história de seis meses de letargia e dispnéia. Ao exame, mostrou-se pálido, sem hepatoesplenomegalia. A concentração de hemoglobina foi de 3g/dl, com acentuada anisocitose, mas sem "células em lágrimas". Os aspirados de medula óssea mostraram-se "secos", enquanto a biópsia revelou hipercelularidade e fibrose grau IV, obliterando a arquitetura habitual. Os megacariócitos estavam em número aumentado, com morfologia anômala, reagindo com anticorpos antifator VIII e CD31. Com a introdução de prednisona 1mg/kg em junho de 1996, os sintomas reduziram, a hemoglobina elevou-se e a fibrose cedeu para grau II, tornando-se independente de transfusões até janeiro de 1999. Então, a hemoglobina caiu para 6g/dl e, com a introdução de prednisona, houve pronta elevação da hemoglobina.

Context: Bone marrow fibrosis is observed in different clonal hematological disorders including myeloproliferative diseases, acute leukemias and myelodysplastic syndromes. In myelodysplastic syndrome a new clinical-pathological entity with significant increase in reticulin fibers has been suggested, and the term hyperfibrotic myelodysplasia was used to define it. Bone marrow biopsy shows increased reticulin fibers, megakaryocytic hyperplasia and dysplasia. Differential diagnosis with primary myelofibrosis may be difficult and hybrid cases may occur. Patients with hyperfibrotic myelodysplastic syndrome responding to treatment with steroids have been reported. In the majority of cases there was only hematological remission, although resolution of fibrosis occurred in one patient. Design: Case report. Case report: A 62-year old male presented in June 95 with a 6-month history of lethargy and dispnea. On examination he was pale without hepato-splenomegaly. Hemoglobin concentration was 3g/dL with marked anisocytosis without teardrop cells. Bone marrow aspirates resulted in dry tap. Bone marrow biopsy showed hypercellularity with increased fibrosis (grade IV) obliterating the normal marrow architecture. Megakaryocytes were increased in number, with abnormal morphology. Monoclonal antibodies against factor VIII and CD31 revealed that both were expressed in megakaryocytes. Prednisone (1mg/Kg) was introduced in June 1996, after what his symptoms lessened and hemoglobin increased. Bone marrow fibrosis decreased (grade IV to grade II). He has become transfusion independent till Jan/1999, when hemoglobin fell to 6g/dL and prednisone was reintroduced with a prompt rise in hemoglobin concentration.

CONTEXTO: Diversas variáveis clínicas se relacionam ao prognóstico na leucemia linfocítica crônica; no entanto, o estadiamento de Binet determina melhor o prognóstico do que o estadiamento de Rai e Rai modificado. OBJETIVO: Avaliar características clínicas e laboratoriais no prognóstico da leucemia linfocítica crônica. TIPO DE ESTUDO: Estudos de correlação. LOCAL: Universidade Federal de São Paulo - Escola Paulista de Medicina / Universidade de Alfenas. PARTICIPANTES: 73 patients diagnosticados entre 1977 e 1994. VARIÁVEIS ESTUDADAS: Sexo, origem étnica, idade, linfadenomegalia, esplenomegalia, hepatomegalia, três ou mais áreas com aumento linfóide, hemoglobina, linfocitos, plaquetas. RESULTADOS: A sobrevida média dos pacientes foi 76 meses, idade média de 65 anos, variando de 33 a 87 anos. Quarenta e quatro pacientes (60,3%) eram do sexo masculino e 29 (39,7%) do sexo feminino. A análise univariada mostrou que o nível de hemoglobina (P = 0,001), número de plaquetas (P = 0,03), linfocitose periférica (P = 0,03), número de áreas linfóides acometidas (P = 0,01), assim como os estadiamentos de Rai (P = 0,02), Rai modificado (0,007) e Binet (P = 0,003) relacionaram-se significantemente com a sobrevida. A análise multivariada, pela regressão de Cox, demonstrou que o sistema de Binet determina melhor o prognóstico do que os estadiamentos de Rai e Rai modificado. CONCLUSÃO: O estadiamento de Binet é melhor que o estadiamento de Rai e Rai modificado na determinação do prognóstico.

CONTEXT: Chronic lymphocytic leukemia (CLL) is a clonal lymphoproliferative disorder, characterized by B lymphocytic proliferation. CLL is the most frequent adult leukemia in Western countries, accounting for 25 to 30% of all white leukemic patients. OBJECTIVE: To evaluate clinical and staging characteristics in prognosis of chronic lymphocytic leukemia. DESIGN: Evaluation of clinical-staging data. SETTING: Universidade Federal de São Paulo - Escola Paulista de Medicina / Universidade de Alfenas. SAMPLE: 73 patients diagnosed from 1977 to 1994. MAIN MEASUREMENTS: Sex, ethnic origin, age, lymphadenopathy, splenomegaly, hepatomegaly, three or more areas of lymphoid enlargement, hemoglobin (g/dl), lymphocytes/mm³, Platelets/mm³ RESULTS: Mean survival of patients was 76 months, median age was 65 years, ranging from 33 to 87. Forty-four patients (60.3%) were male and 29 (39.7%) female. CONCLUSION: The Binet system determined a better prognosis than Rai.

As principais causas de inflamação pancreática no mundo são a litíase biliar e o alcoolismo crônico. Admite-se que 10 a 30% das pancreatites agudas sejam idiopáticas. Sugere-se que parte destas são causadas por microlitíase ou barro biliar, identificados pela presença de microcristais no sedimento biliar. Neste estudo, realizou-se análise microscópica da bile obtida por colangiopancreatografia endoscópica, em pacientes com pancreatite aguda idiopática, pancreatite aguda biliar e pancreatite crônica alcoólica - 20 em cada grupo. Pacientes com pancreatite aguda idiopática e microcristais na bile foram submetidos a colecistectomia. Naqueles inaptos à cirurgia efetuou-se esfincterotomia endoscópica ou tratamento com ácido ursodesoxicólico. Pacientes com pancreatite aguda idiopática sem cristais não receberam tratamento específico. A prevalência de microcristais biliares em pacientes com pancreatite aguda idiopática (75%) e pancreatite aguda biliar (90%) foi significativamente maior que naqueles com pancreatite crônica alcoólica (15%). A detecção de microcristais apresentou sensibilidade de 90%, especificidade de 85%, valor preditivo positivo de 85,7%, valor preditivo negativo de 89,4% e acurácia de 87,5% em identificar pancreatite de origem biliar. Nos pacientes com pancreatite aguda idiopática recurrente, cursando com microcristais, houve redução significante dos episódios de pancreatite após tratamento específico. No seguimento deste grupo durante 23,3 meses, recidiva ocorreu apenas naqueles que apresentavam "fator biliar persistente" (coledocolitíase ou microcristais). Todos os pacientes com pancreatite aguda idiopática submetidos a colecistectomia apresentavam colecistite crônica, e microlitíase foi observada em um paciente. No seguimento ultra-sonográfico, colelitíase foi detectada em um dos casos. No subgrupo de cinco pacientes com pancreatite aguda idiopática sem microcristais houve uma recidiva. Estudo ultra-sonográfico durante o seguimento não revelou cálculo biliar em nenhum destes. Concluiu-se que a detecção de microcristais biliares na pancreatite aguda idiopática sugeriu etiologia biliar oculta subjacente. Adicionalmente, intervenção terapêutica específica nos pacientes com pancreatite aguda idiopática recurrente e microcristais reduziu as recidivas durante o seguimento. Finalmente, pancreatite aguda (particularmente, recurrente) não deveria ser rotulada como idiopática antes da análise microscópica da bile visando a detecção ou exclusão da presença de microcristais.

The main causes of pancreatic inflammation worldwide are biliary lithiasis and alcoholism. However, 10 to 30% of patients have been considered to have "idiopathic" acute pancreatitis. Recently, some studies showed that a significant rate of the so called idiopathic pancreatitis are caused by microlithiasis and/or biliary sludge, identified by the presence of cholesterol monohidrate and/or calcium bilirubinate microcrystals in the biliary sediment. In the present study, the analysis of microcrystals from bile obtained during endoscopic retrograde cholangiopancreatography was done in patients with pancreatitis (idiopathic, biliary or alcoholic -- 20 in each group). Patients with idiopathic pancreatitis and microcrystals in the bile underwent cholecystectomy whenever possible. Those who refused or were inapt to surgery underwent endoscopic sphincterotomy or received continuous therapy with ursodeoxycholic acid. Patients with idiopathic pancreatitis without biliary crystals did not receive any specific treatment. The prevalence of biliary microcrystals in patients with idiopathic pancreatitis (75%) and biliary pancreatitis (90%) was significantly higher than in those with alcoholic pancreatitis (15%). In the identification of the etiology of biliary pancreatitis, the presence of microcrystals had a sensitivity of 90%, specificity of 85%, positive predictive value of 85,7%, negative predictive value of 89,4% and accuracy of 87,5%. In the patients with recurrent idiopathic pancreatitis, with biliary crystals, there was an statistically significant reduction in the number of pancreatitis episodes after specific treatment. In the follow-up of this group during 23,3 ± 4,8 months, recurrence of pancreatitis occurred only in patients with "persistent biliary factor" (choledocholithiasis and/or persistence of cholesterol monohidrate). All patients with idiopathic pancreatitis who underwent cholecystectomy had chronic cholecystitis. Moreover, cholelithiasis was present in one case. In the ultrassonographic follow-up of the patients with idiopathic acute pancreatitis with microcrystals in the bile, cholelithiasis was detected in one case. In the subgroup of five patients with idiopathic pancreatitis without biliary microcrystals recurrence occurred in one case. Ultrassonographic study during follow-up did not reveal biliary stones in any of these patients. We concluded that the detection of biliary microcrystals in "idiopathic" pancreatitis suggested an underlying biliary etiology, even if occult. What's more, early specific therapeutic procedure (cholecystectomy, endoscopic sphincterotomy or ursodeoxycholic acid) in patients with recurrent idiopathic pancreatitis with microcrystals in the bile reduced significantly the recurrence during the follow-up. Finally, acute pancreatitis (specially recurrent) should not be called idiopathic before the microscopic analysis of the bile, aiming to detect or exclude the presence of microcrystals.

CONTEXTO: Na doença de Hodgkin, cada estágio clínico ou patológico pode ser relacionado com a extensão da área envolvida e predizer a próxima região anatômica de risco para disseminação. OBJETIVO: Estabelecer os fatores prognósticos que melhor predizem sobrevida em LNH. TIPO DE ESTUDO: Estudo retrospectivo LOCAL: Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo - Escola Paulista de Medicina. PARTICIPANTES: 142 pacientes com LNH diagnosticados entre fevereiro de 1988 e março de 1993. VARIÁVEIS ESTUDADAS: Tipo histológico, sexo, idade, raça, sintomas, sitação "performance", estágio, doença extranodal, desenvolvimento de Bulk, comprometimento mediastinal, envolvimento do SNC, infiltração da medúla óssea, nível de desidrogenose láctica, fenótipo imune. RESULTADOS: Ao primeiro estudo (113 pacientes), as seguintes variáveis tiveram uma pior influência na sobrevida: raça amarela (P<0.1); ECOG II, III e IV (P<0.1) e doença extranodal (P<0.1) para os linfomas de alto grau; sintomas constitucionais (P<0.1), ECOG II, III e IV (P<0.1) e envolvimento de SNC (P<0.1) para os linfomas de grau intermediário e o subtipo linfoplasmocitóide (P=0.0186) para os linfomas de baixo grau. Ao segundo estudo (93 pacientes), quando inclui-se o tratamento, as variáveis relacionadas a sobrevida foram : envolvimento de SNC (P<0.1) para o linfomas de alto grau; sintomas constitucionais (P<0.1), ECOG II, III, IV (P=0.0185) e envolvimento de SNC (P<0.1) para o grupo intermediário. Nenhuma variável relacionou-se com a sobrevida para os linfomas de baixo grau. CONCLUSÕES: Os linfomas de grau intermediário, provavelmente devido ao maior número de pacientes, foram mais compatíveis com os dados encontrados na literatura. Neste caso específico, o tratamento não influenciou a sobrevida.

CONTEXT: In Hodgkin's disease, each clinical or pathologic stage can be related to the extent of the area involved and predicts the next anatomical region at risk for tumor dissemination. OBJECTIVE: To determine the best prognostic factors that could predict survival in non-Hodgkin lymphoma cases. DESIGN: A retrospective study. LOCATION: Department of Hematology and Transfusion Medicine, Universidade Federal de São Paulo - Escola Paulista de Medicina. PARTICIPANTS: 142 patients with non-Hodgkin lymphoma diagnosed between February 1988 and March 1993. MAIN MEASUREMENTS: Histological subset, Sex, Age, Race, B symptoms, Performance status, Stage, Extranodal disease, Bulk disease, Mediastinal disease, CNS involvement, BM infiltration, Level of DHL, Immunophenotype. RESULTS: In the first study (113 patients), the following variables had a worse influence on survival: yellow race (P<0.1); ECOG II, III e IV (P<0.1) and extranodal disease (P<0.1) for high grade lymphomas; constitutional symptoms (P<0.1), ECOG II, III e IV (P<0.1) and involvement of CNS (P<0.1) for intermediate grade and the subtype lymphoplasmocytoid (P=0.0186) for low grade lymphomas. In the second survey (93 patients), when treatment was included, the variables related to NHL survival were: CNS involvement (P<0.1) for high grade lymphomas, constitutional symptoms (P<0.1), ECOG II, III, IV (P=0.0185) and also CNS involvement (P<0.1) for the intermediate group. There were no variables related to the survival for low-grade lymphomas. CONCLUSIONS: The intermediate grade lymphomas were more compatible with data found in the literature, probably because of the larger number of patients. In this specific case, the treatment did not have an influence on the survival.

OBJETIVO: Avaliar utilidades dos sistemas de escore de Cassano e Sanz e propor outro. DESENHO: Serie de Casos. LOCAL: Hospitais universitários: EPM-UNIFESP e Faculdade de Medicina de Botucatu. PARTICIPANTES: 59 pacientes diagnosticados entre 1979 e 1992. INTERVENÇÃO: Avaliação de parâmetros clínico-laboratoriais. MENSURAÇÃO: Comparação estatística, análise uni e multivariada e curva de sobrevida atuarial. RESULTADOS: O sistema de Cassano dividiu os pacientes em alto e baixo risco (p=0.0966) enquanto o de Sanz em alto, intermediário e baixo risco (p=0.0108). A análise univariada demonstrou que hemoglobina, contagem de GB, relação EM, aumento do fígado e % de blastos na medula (MO) eram estatisticamente significantes. A regressão multivariada demonstrou como sendo significantes a % de blastos da MO (p=0.004) e os níveis de Hb (p=0.050). O nosso sistema, considerando os parâmetros da análise univariada, dividiu os pacientes em alto, intermediário e baixo risco (p=0.0038). CONCLUSÕES: O sistema de Sanz foi mais prático que o de Cassano enquanto o nosso, demonstrou valor preditivo de sobrevida e uso fácil na prática clínica.

OBJECTIVE: To evaluate the score systems of Cassano and Sanz and suggest a new one. DESIGN: Case series. LOCATION: Teaching hospitals: EPM UNIFESP and Faculdade de Medicina de Botucatu. PARTICIPANTS: 59 patients diagnosed from 1979 to 1992. INTERVENTION: Evaluation of clinical-laboratorial data. MEASUREMENT: Statistical comparison, uni and multivariate analysis and actuarial survival curves. RESULTS: Cassano's system divided the patients into high and low risk (p=0.0966) while, Sanz's gave high, intermediate and low risk (p=0.0108). The univariate analysis showed hemoglobin, WBC count, E/M ratio, liver size and blast percentage in BM as statistically significant. The multivariate analysis showed blast percentage in BM (p=0.004) and Hb (p=0.050) as significant. Our system, considering the multivariate analysis data, divided the patients into high, intermediate and low risk (p=0.0038). CONCLUSIONS: Sanz's system was more functional than Cassano's, while ours showed predictive survival value and ease of use in clinical practice.

Avaliamos o valor prognóstico de diferentes fatores, ao diagnóstico, em 45 pacientes com LMC Ph1-positivos. A sobrevida mediana foi de 48 meses. A análise univariada identificou 5 fatores associados a pior prognóstico (sexo masculino, idade inferior a 45 anos, blastos na medula óssea maior ou igual a 10 percent, basófilos no sangue periférico maior ou igual a 6 percent e eosinófilos no sangue periférico maior ou igual a 6 percent), originando um sistema de estadiamento: estágio I com zero ou um fator e sobrevida de 100 percent em dois anos; estágio II com dois ou três fatores e sobrevida de 72,2 percent em dois anos; estágio III com 4 ou 5 fatores e sobrevida de 0 percent em dois anos (p = 0.00016). A análise multivariada demonstrou que a basofilia no sangue periférico e os blastos na medula óssea foram os fatores que melhor se correlacionaram com o tempo de sobrevida. Concluímos que a combinaçóo de fatores presentes no diagnóstico permite a identificação de diferentes grupos de risco na LMC, podendo ser útil na determinaçóo do prognóstico e na abordagem terapêutica.

The prognostic value of different factors upon diagnosis of CML was analysed in 45 Philadelphia (Ph1)-positive patients. The median survival was 48 months. Univariate analysis showed 5 poor prognostic factors (male sex, under 45 years-old, bone marrow blasts greater than or equal to 10 percent, blood basophils greater than or equal to 6 percent and blood eosinophils greater than or equal to 6 percent) which provided for the development of a clinical staging system: Stage I with none or one factor and a two-year survival rate of 100 percent; Stage II with two or three factors and two-year survival of 72.2 percent; and Stage III with four or five factors and two-year survival of 0 percent (p = 0.00016). Multivariate survival analysis showed that combination of blood basophilia and bone marrow blasts had the strongest predictive relationship to survival time. We conclude that a combination of pretreatment factors identifies different risk subcategories in CML patients and is helpful in assessing the overall prognosis and the treatment approach.