As síndromes mielodisplásicas (SMD) são um grupo das doenças clonais de células-tronco caracterizado por hematopoese ineficaz, hiperproliferação de medula óssea, citopenias no sangue periférico e risco de transformação para leucemia aguda. Decidimos investigar os efeitos de um concentrado de soja em pacientes com SMD com base no fato de termos o seguimento de uma paciente japonesa, de 61 anos de idade, que foi diagnosticada em 2003 com SMD, citopenia refratária com displasia subtipo multilinhagens (hemoglobina = 11 g/dL; contagem de glóbulos brancos = 2.500/uL e plaquetas = 25.000/uL; medula com displasia leve e cariótipo normal; hemoglobinúria paroxística excluída), e que começou a usar a soja como suplemento alimentar em maio de 2004, apresentando gradual aumento da contagem das células sanguíneas, atingindo a normalização cerca de oito meses depois. Entre os componentes da soja, os principais compostos com propriedades anticarcinogênese são as isoflavonas (Ge nisteína e daidzeína). Com base nessas linhas de evidência, foi proposto oferecer diariamente um concentrado de soja padrão, por um período mínimo de três meses e máximo de doze meses, a 14 pacientes ambulatoriais, na tentativa de avaliar, prospectivamente, o possível aumento de hemoglobina, neutrófilos e plaquetas. Um grupo controle histórico foi utilizado para comparar os resultados. O uso de um concentrado de soja de forma padronizada foi associado ao aumento na contagem de neutrófilos e/ou de plaquetas em alguns casos, mas aumentos espontâneos também foram observados em controles históricos. Este estudo preliminar não permite estabelecer relação entre o uso de soja e o aumento na contagem sanguínea.

Myelodysplastic syndromes (MDS) are a group of clonal stem cell diseases characterized by ineffective hematopoiesis, bone marrow hyperproliferation, cytopenias in peripheral blood and risk of transformation into acute leukemia. We decided to investigate the effects of a soy concentrate on MDS patients based on the follow-up results of a 61 year-old Japanese female patient who was diagnosed with MDS and refractory cytopenia with multilineage dysplasia in 2003 (hemoglobin = 11g/dL; white blood cells count = 2,500/uL and platelets = 25,000/uL; marrow with mild dysplasia and normal karyotype; paroxysmal nocturnal hemoglobinuria was excluded). She started using soy as a dietary supplementation in May 2004 and presented a gradual increment in blood counts, achieving normalization approximately eight months afterwards. Among the soy components, the main compounds with anti-carcinogenic activity are the isoflavones (genistein and daidzein). Based on these lines of evidence, we proposed to administer daily a standard soy concentrate to 14 MDS out-patients for a minimum period of three months and maximum of 12 months, in an attempt to evaluate prospectively the possible increase in hemoglobin, neutrophils and platelet counts. A historical control group was used to compare results. The use of a soy concentrate in a standardized manner was associated with an increase in neutrophil and/or platelet counts in some cases, but spontaneous increments were also observed in historical controls. This preliminary study does not allow establishing a relation between soy supplementation and blood cell count increase.

The expression of P53, Bcl-2, Bax, Bag-1, and Mcl-1 proteins in CD5/CD20-positive B-chronic lymphocytic leukemia (B-CLL) cells from 30 typical CLL patients was evaluated before and after 48 h of incubation with 10-6 M fludarabine using multiparametric flow cytometric analysis. Protein expression was correlated with annexin V expression, Rai modified clinical staging, lymphocyte doubling time, and previous treatment. Our main goal was to determine the predictive value of these proteins in CLL cells in terms of disease evolution. Bcl-2 expression decreased from a median fluorescence index (MFI) of 331.71 ± 42.2 to 245.81 ± 52.2 (P < 0.001) after fludarabine treatment, but there was no difference between viable cells (331.57 ± 44.6 MFI) and apoptotic cells (331.71 ± 42.2 MFI) before incubation (P = 0.859). Bax expression was higher in viable cells (156.24 ± 32.2 MFI) than in apoptotic cells (133.56 ± 35.7 MFI) before incubation, probably reflecting defective apoptosis in CLL (P = 0.001). Mcl-1 expression was increased in fludarabine-resistant cells and seemed to be a remarkable protein for the inhibition of the apoptotic process in CLL (from 233.59 ± 29.8 to 252.04 ± 35.5; P = 0.033). After fludarabine treatment, Bag-1 expression was increased in fludarabine-resistant cells (from 425.55 ± 39.3 to 447.49 ± 34.5 MFI, P = 0.012), and interestingly, this higher expression occurred in patients who had a short lymphocyte doubling time (P = 0.022). Therefore, we could assume that Bag-1 expression in such situation might identify CLL patients who will need treatment earlier.

The purpose of this paper is the study of fuzzy control applied to a Dynamic Positioning System (DPS) of semi-submersible platforms. A numerical simulator program in time domain was coded using mathematical models of the floating platform dynamics and the external forces (wind, current, wave and thruster) that act on the platform. Subsequently, a fuzzy controller applied to DPS was developed. The Fuzzy controller and the Proportional-Integral-Derivative (PID) controller were then subjected to the same environmental conditions in order to compare their performance.

Acute myeloid leukemia (AML) is a disease predominantly of older adults. Treatment of AML in the elderly is complicated not only by comorbidities but also by the high prevalence of poor prognosis markers. Thirty-one consecutive unselected patients with AML older than 60 years (representing 33% of all AML cases diagnosed at our institution during the same period) were followed over a period of 5 years (1997-2002). A high incidence of AML with multilineage dysplasia (45%) and no favorable cytogenetic abnormalities but 62% intermediate and 38% unfavorable karyotypes were found. Sixteen patients (52%) were selected for induction of intensive cytotoxic treatment and complete remission was achieved only by some of these intensively treated patients (7 of 16). Of these, 3 remained alive without disease (median: 11 months), 1 patient died shortly after complete remission, and 3 patients relapsed and died from refractory disease. Only 1 patient that was refractory to intensive cytotoxic treatment remained alive with disease under supportive care. Fifteen patients (48%) were managed with palliative/supportive care: 7 received palliative treatment and supportive care, 8 received supportive care only, and 4 patients remained alive with disease under supportive care (median: 9 months). Mortality rate was 74% and overall survival at two years was 12%. To the best of our knowledge, there is no previous report regarding elderly patients with AML in Brazilian subsets. The present data are similar to previously reported studies showing that elderly AML patients are not only older but also biologically distinct from younger AML patients, particularly in terms of the high incidence of poor prognostic karyotypes and resistance to therapy.

Acute promyelocytic leukemia (AML M3) is a well-defined subtype of leukemia with specific and peculiar characteristics. Immediate identification of t(15;17) or the PML/RARA gene rearrangement is fundamental for treatment. The objective of the present study was to compare fluorescent in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR) and karyotyping in 18 samples (12 at diagnosis and 6 after treatment) from 13 AML M3 patients. Bone marrow samples were submitted to karyotype G-banding, FISH and RT-PCR. At diagnosis, cytogenetics was successful in 10 of 12 samples, 8 with t(15;17) and 2 without. FISH was positive in 11/12 cases (one had no cells for analysis) and positivity varied from 25 to 93% (mean: 56%). RT-PCR was done in 6/12 cases and all were positive. Four of 8 patients with t(15;17) presented positive RT-PCR as well as 2 without metaphases. The lack of RT-PCR results in the other samples was due to poor quality RNA. When the three tests were compared at diagnosis, karyotyping presented the translocation in 80% of the tested samples while FISH and RT-PCR showed the PML/RARA rearrangement in 100% of them. Of 6 samples evaluated after treatment, 3 showed a normal karyotype, 1 persistence of an abnormal clone and 2 no metaphases. FISH was negative in 4 samples studied and 2 had no material for analysis. RT-PCR was positive in 4 (2 of which showed negative FISH, indicating residual disease) and negative in 2. When the three tests were compared after treatment, they showed concordance in 2 of 6 samples or, when there were not enough cells for all tests, concordance between karyotype and RT-PCR in one. At remission, RT-PCR was the most sensitive test in detecting residual disease, as expected (positive in 4/6 samples). An incidence of about 40% of 5' breaks and 60% of 3' breaks, i.e., bcr3 and bcr1/bcr2, respectively, was observed.

Os autores relatam um caso de leucemia mielóide aguda (LMA) que apresentava, ao diagnóstico, basofilia no sangue periférico e cariótipo com presença do cromossomo Filadélfia (Ph1). Após um ano de tratamento com quimioterapia intensiva e em fase de remissão clínica e hematológica, a análise molecular pela técnica da reação em cadeia da polimerase-transcriptase reversa (RT-PCR) revelou presença de doença residual (rearranjo b2-a2). A seguir, o paciente apresentou primeira recidiva como LMA e, após a remissão, evoluiu com quadro hematológico sugestivo de leucemia mielóide crônica (LMC) em fase crônica. Após dez meses, apresentou nova recidiva da LMA. Os autores discutem a dificuldade do diagnóstico diferencial entre LMA Ph1-positivo de novo e crise blástica mielóide como primeira manifestação clínica da LMC, baseados nos aspectos clínicos e moleculares.

A case of AML presented with basophilia in peripheral blood and Ph1 chromosome in karyotype analysis is reported. After one year of treatment with intensive chemoterapy and clinical and hematological remission, molecular analysis (RT-PCR) detected minimal residual disease (b2-a2 rearrangement). Thus, the patient relapsed as AML and, after second remission, he developed a hematological picture of chronic CML. Ten months later, he relapsed again as AML. The difficulties of diagnosis between AML Ph1-positive de novo and myeloid blast crisis of CML, as the first manifestation of disease, based on clinical and molecular aspects are discussed.

A necrólise epidérmica tóxica é afecção dermatológica secundária ao uso de drogas e corresponde à síndrome de Lyell, relacionada ao eritema multiforme e à síndrome de Stevens-Johnson. OBJETIVOS: Relatar um caso de necrólise epidérmica fatal secundária à citosina-arabinosídeo (Ara-C) em dose intermediária. RELATO DE CASO: Paciente do sexo feminino, com 16 anos de idade, portadora de leucemia linfóide aguda - LLA-L1. Iniciou tratamento segundo o protocolo do Grupo Brasileiro de Tratamento da Leucemia Infantil/85, alto risco. Na fase II da indução, após o uso de Ara-C na dose de 1,5g/m², intravenoso, 12/12h x três dias, desenvolveu múltiplas lesões cutâneas bolhosas, que aumentaram rapidamente por progressão das bordas. As bolhas continham secreção serosa, evoluíram para ulceração superficial central, com infecção secundária múltipla. Faleceu por septicemia, no 13º dia após o início do quadro dermatológico. CONCLUSÃO: O Ara-C tem sido relacionado a diversas manifestações de toxicidade dermatológica; no entanto, até o momento, não há relato de necrólise epidérmica tóxica, sendo este o primeiro caso da literatura.

Toxic epidermal necrolysis is a drug-induced dermatologic disease related to Lyell syndrome, erythema multiforme and Stevens-Johnson syndrome. PURPOSE: To report a fatal case of toxic epidermal necrolysis owing to intermediate dose of cytarabine. CASE REPORT: A 16 year-old female patient with acute lymphocytic leukemia (LLA-L1) treated with the Protocol of the Brazilian Group for Treatment of Leukemia of Childwood (GBTLI-85-AR). On the second day after the administration of intermediate dose of cytarabine (1.5g/m² IV every 12 hours for 3 days), she presented bullous lesions in the left buttock that disseminated envolving to necrosis, sepsis, and death on the 13th day. CONCLUSION: Cytarabine is frequently associated with dermatologic toxicity but, until now, there is no other case of toxic epidermal necrolysis described.