Our observation of a 4.7-fold (95% CI: 2.1-11.0) and 2.3-fold (95% CI: 1.0-5.2) increased risk associated with the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6-fold (95% CI: 2.4-7.9) increased risk associated with the combined null genotype presents preliminary evidence that the inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.

The fractal nature of the DNA arrangement has been postulated to be a common feature of all cell nuclei. We investigated the prognostic importance of the fractal dimension (FD) of chromatin in blasts of patients with acute precursor B lymphoblastic leukemia (B-ALL). In 28 patients, gray scale transformed pseudo-3D images of 100 nuclei (May–Grünwald–Giemsa stained bone marrow smears) were analyzed. FD was determined by the Minkowski–Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R2 values in the log-log plots. Whereas FD presented no prognostic relevance, patients with higher R2 values showed a prolonged survival. White blood cell count (WBC), age and mean fluorescence intensity of CD45 (MFICD45) were all unfavorable prognostic factors in univariate analyses. In a multivariate Cox-regression, R2, WBC, and MFICD45, entered the final model, which showed to be stable in a bootstrap resampling study. Blasts with lower R2 values, equivalent to accentuated “coarseness” of the chromatin pattern, which may reflect profound changes of the DNA methylation, indicated a poor prognosis. In conclusion the goodness-of-fit of the Minkowski–Bouligand dimension of chromatin can be regarded as a new and biologically relevant prognostic factor for patients with B-ALL.

The expression of p53, p21/WAF-1, Mdm2, c-Myc, and proliferating cell nuclear antigen (PCNA) proteins was examined by the immunohistochemistry of paraffin-embedded tissues of 62 patients with aggressive non-Hodgkin's lymphomas (NHL) and correlated to clinical data. Expression of p53, p21/WAF-1, Mdm2, and c-Myc protein was observed in 17 out of 62 cases (30%), 25 out of 60 (42%), 13 out of 44 (30%), and 39 out of 51 (76.5%), respectively. The p53 + /p21WAF-1 phenotype, which is more frequently found in p53 mutations, was associated with a worse overall survival (P = 0.04) and with a lower rate of complete response (CR) (PF = 0.01). p53 and c-Myc negative expression was related to a better response to chemotherapy (PF = 0.005 and 0.035, respectively). The expression of p53, c-Myc, and Mdm2 was related to a shortened overall survival (P < 0.001, 0.05, and 0.037, respectively), suggesting that the expression of these proteins could be associated with a poor outcome in these patients. Am. J. Hematol. 67:84-92, 2001.

Many efforts have been made to standardize the interpretation of 18 f-fDG pet/ct in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of 18 F-FDG PET/CT considering the extent and intensity of bone 18 F-FDG uptake: Intensity of Bone Involvement (IBI). Whole body 18 F-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with 18 F-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement -PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00-1.35). Visual analysis categorized PET exams into three groups (negative/ mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients' hemoglobin values and IBI (r = −0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting.Lytic bone lesions are reported in approximately 80% of myeloma multiple (MM) patients 1,2 . Early and precise evaluation of bone involvement is crucial for staging and correct disease management.Hybrid image of positron emission tomography with 18 F-fluordeoxyglucose and computed tomography ( 18 F-FDG PET/CT) is one of the main methods for the evaluation of MM patients. It allows whole-body images, intra and extramedullary lesion detection, distinction between active lesions and scar or necrotic tissue and has been more sensitive than MRI in treatment assessment 3-5 .Many efforts have been attempted to standardize the interpretation of 18 F-FDG PET/CT in MM, using qualitative visual analysis or quantitative metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) 6-9 . However, none of these methods have been extensively used in clinical practice or research projects, probably because of the complexity of the visual quantification 6,7 or due to the lack of standardization of MTV and TLG calculations 8-10 . Also, MTV and TLG only consider areas visually defined as lesions and ignore diffuse uptake of the bone marrow.

Aplastic anemia and agranulocytosis are rare diseases in Brazil. However, there is considerable variability in their incidences between different regions.

The association of agranulocytosis with the use of many different drugs has been documented. LATIN is a case-control study designed to identify risk factors for agranulocytosis and aplastic anemia, including drugs, and to estimate the incidence rates of both diseases in some Latin American countries. This report will cover just agranulocytosis. In 4 years, 52 cases of agranulocytosis were diagnosed. The overall incidence rate was 0.38 cases per 1 million inhabitant-years (0.35 for Brazil, 2.09 for Argentina, and no case verified in Monterrey, Mexico). Agranulocytosis patients more often took medications already associated with agranulocytosis than controls (76.7% of cases and 52.5% of controls; OR 3.7, 95% CI 1.3–12.5; p = 0.01), the most important being methimazole (OR 44.2, 95% CI 6.8 to infinite). The population attributable risk percent (etiologic fraction) was 56%. The use of nutrients supplements was more frequent among agranulocytosis patients than controls (p = 0.03). The agranulocytosis incidence in Latin America was lower than that of European countries and Israel. The rarity of the disease indicates that it is not a public health problem, and there is no reason for major protection measures other than improving diagnostic tools and making earlier agranulocytosis diagnosis.

Aims-To study correlations between the pattern of silver stained nucleolar organiser regions (AgNORs) in chronic lymphocytic leukaemia (CLL) and parameters of tumour kinetics. To investigate whether quantitation of the AgNOR pattern can be used to discriminate between patients with stable and progressive disease. Methods-Peripheral blood smears from 48 patients with CLL, classified as having either stable or progressive disease (Rai stage III or IV; bulky lymph nodes or massive splenomegaly; or peripheral lymphocytes >100 x 10911), were studied. For each patient, total tumour mass (TTM) and for patients undergoing a period of observation without treatment, the TTM duplication time (DT) and the lymphocyte doubling time (LDT) were calculated.

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