T-cell malignancies in Brazil have a high seroprevalence rate of HTLV-I antibodies. We have analyzed the disease features in 188 Brazilian patients with a T-cell disorder. These included 40 with T-lymphoblastic leukaemia or lymphoma (T-ALL/T-LbLy) and 148 with mature T-cell diseases: 5 T-prolymphocytic leukaemia, 53 adult T-cell leukaemia/lymphoma (ATLL), 54 cutaneous T-cell lymphomas, 29 pleomorphic T-cell lymphomas and 7 large granular lymphocyte leukaemia. The diagnosis was based on clinical, morphological and immunological features and HTLV-I serology. ATLL in Brazil has the same diseases features as in other endemic regions, the only apparent differences being: age, Brazilian patients being younger than Japanese, and ethnic grouping, one third of Brazilians being white Caucasians of European descent. We applied a scoring system based on the presence or absence of typical features associated with ATLL; hypercalcaemia, cell morphology, immunophenotype, histopathology and HTLV-I status, to see whether it may help in diagnosing cases of ATLL. All had high scores, whereas all other T-cell diseases scored low. Only 5 ATLL cases were HTLV-I-negative by serology, but they had otherwise typical features of ATLL, and their cells did not have HTLV-I proviral sequences by DNA analysis. Such cases suggest that ATLL may develop in a minority of individuals living in regions where it is endemic, without evidence of HTLV-I infection, and that other factors may contribute to the pathogenesis of the disease.

Forty-five individuals with hepatosplenic schistosomiasis mansoni were studied with the aim of measuring levels of von Willebrand factor antigen (vWF:Ag), detecting abnormalities in platelet morphology and aggregation, and identifying changes to surface antigens. Haemograms, platelet aggregation tests, flow cytometry investigations of CD41/CD42b antibody and vWF:Ag assays were performed. Mean platelet counts were low (77,522/mm3) and 82.2% of patients presented thrombocytopenia. An inverse relationship between spleen size and platelet count was seen. Macroplatelets were found in 57.1% of patients, indicating good bone-marrow response, but were insufficient to compensate for the decrease in platelets due to splenomegaly. Decreased or absent platelet aggregation was seen in 50% of patients, probably due to low platelet counts. Markers for GPIIb/IIIa were normal in more than 90% of patients, not supporting the increased capture and destruction of platelets in the spleen that is hypothesized to occur with cirrhosis. Similar to cirrhosis, vWF:Ag levels were high or very high in 70.5% of patients. High levels of vWF:Ag were associated with platelet counts <100,000/mm3, larger spleen diameter and oesophageal varices. In conclusion, hepatosplenic schistosomiasis leads to a lower platelet count due to pooling in the spleen and, consequently, impaired aggregation, but not to increased capture and destruction of platelets in the spleen. High vWF:Ag levels probably promote stabilization of platelet microaggregates and prevent minor manifestations of thrombocytopenia such as petechiae, ecchymosis and gingival bleeding.

Stroke is a catastrophic complication of sickle cell anaemia (SCA) and is one of the leading causes of death in both adults and children with SCA. Evidence suggests that some genetic polymorphisms could be related to stroke development, but their association remains controversial. Here, we performed genotyping of five published single nucleotide polymorphisms, the α-thalassemia genotype, the G6PD A (-) variant deficiency, and the β(S) haplotype in a large series of SCA patients with well-defined stroke phenotypes. Of 261 unrelated SCA patients included in the study, 67 (9.5 %) presented a documented, primary stroke event. Markers of haemolysis (red blood cell (RBC) counts, p = 0.023; reticulocyte counts, p = 0.003; haemoglobin (Hb) levels, p < 0.001; indirect bilirubin levels, p = 0.006; lactate dehydrogenase (LDH) levels, p = 0.001) were associated with stroke susceptibility. Genetically, only the β(S) haplotype (odds ratio (OR) 2.9, 95 % confidence interval (CI) 1.56 to 4.31; p = 0.003) and the α(3.7kb)-thalassemia genotype (OR 0.31, 95 % CI 0.11 to 0. 83; p = 0.02) were associated with increased and decreased stroke risk, respectively. In multivariate analysis, the β(S) haplotype was independently associated with stroke development (OR 2.26, 95 % CI 1.16 to 4.4; p = 0.016). Our findings suggest that only the β(S) haplotypes and the α(3.7kb)-thalassemia genotype modulate the prevalence of stroke in our SCA population. Genetic heterogeneity among different populations may account for the irreproducibility amongst different studies.

Patients were classified according morphologic, immunophenotypic, and cytogenetic findings. Treatment protocols were similar between centers. For patients up to 60 years of age, the treatment protocol was adapted according to performance status and the presence of comorbidities (in particular, cardiac disorders). Briefly, the conventional chemotherapy consisted of daunorubicin (45-90 mg/m 2 per day for 3 days) and cytarabine (100-200 mg/m 2 per day for 7 days) or thioguanine, cytosine arabinoside, and daunorubicin as induction, 1 followed by 3 or 4 cycles of consolidation therapy with high doses of cytarabine (.1 g/m 2 per day). For patients who did not achieve complete remission (CR) after 1 course of chemotherapy, a second course was administered between days 28 and 35 after the end of the first course. CR was assessed by bone marrow examination on day 28 after each course of chemotherapy. For those who needed it, a postremission therapy based on autologous or allogeneic transplantation was performed. Patients older than 60 years were treated with low-dose cytarabine; a combination of etoposide, thioguanine, and idarubicin; or best supportive care. The local research ethics board of each participating center approved the study. Research was conducted in accordance with the Declaration of Helsinki.The baseline characteristics are summarized in supplemental Table 1. One hundred thirty patients were enrolled in Recife (northeast Brazil, 54%), and 111 patients were enrolled in Campinas (southeast Brazil, 46%). Baseline features were similar between centers. The median age was 47 years (range, 18-97 years) with 114 males (47%). Sixty-two patients (26%) were older than 60 years. Pretreatment bone marrow samples were analyzed by G-banding cytogenetics, of which 187 (78%) were successful. According to Medical Research Council trials, 2 patients were stratified as follows: favorable (30/187, 16%), intermediate (119/187, 64%), and adverse (38/187, 20%). Overall, 101 patients (42%) were cytogenetically normal. To test whether the samples without cytogenetics results were missing at random, the overall survival (OS) was evaluated for patients with and without cytogenetics data. The 5-year OS rate did not differ between patients with (18%) and without (23%) available cytogenetics data (P 5 .372). Additionally, the entire cohort was fully characterized for NPM1 and FLT3-ITD mutations. Details can be found in the supplemental Data, available on the Blood Web site.Out of 241 enrolled patients, 39 patients (16%) who started the induction treatment were lost to follow-up without assessment for CR. Of 202 evaluable patients, 115 (57%) achieved complete hematologic remission. CR rates according to the cytogenetic risk stratification were 33%, 64%, and 77% for adverse, intermediate, and favorable groups, respectively (P 5 .001). The logistic regression analysis revealed that age (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.93-0.98; P 5 .002) and cytogenetic risk stratification (OR, 0.41; 95% CI, 0.19-0.89; P 5 .024) wer...

Acute promyelocytic leukemia (APL) is characterized by the presence of rearrangements involving the retinoic acid receptor alpha (RARalpha) gene and a variable incidence in different populations. The hybrid gene PML-RARalpha, present in 98% of cases, encodes a fusion protein essential to the pathogenesis of the disease. Depending of the PML's gene breakpoint in chromosome 15, the transcript subtypes bcr1, bcr2 and bcr3 may be formed. The correlation between these transcript subtypes and clinical parameters is still controversial. The objective of this study was to determine the frequencies of the PML-RARalpha transcripts and subtypes in a series of 32 APL patients from Northeast Brazil and to evaluate the association of these subtypes to different parameters. The method used was RT-PCR. The frequency of our APL cases is approximately 28% of the acute leukemias. The results showed the presence of PML-RARalpha isoform in all patients and a higher frequency of the bcr1/2 subtype. No significant statistical association was found between molecular subtypes and age, sex, French-American-British (FAB) classification, leukocyte and platelet count, hemoglobin level or coagulation tests. In conclusion, these data suggest similar molecular and biological features for our APL patients at diagnosis in comparison with those reported in current scientific literature.