Bone marrow histology in marginal zone B-cell lymphomas: correlation with clinical parameters and flow cytometry in 120 patients

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High Frequency of Endothelial Colony Forming Cells Marks a Non-Active Myeloproliferative Neoplasm with High Risk of Splanchnic Vein Thrombosis

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54–17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×109/L or lower, and platelet count of 400×109/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45–13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment

Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation : A GITMO study

Background: Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified. Design and Methods: We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007. Results: Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P=0.017) and increased non-relapse mortality (hazard ratio=1.68, P=0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P=0.003; non-relapse mortality: hazard ratio=1.70, P=0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation (P=0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft-versus-host disease (P=0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival (P=0.01) and non-relapse mortality (P=0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload. Conclusions: Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non-relapse mortality. These results indicate that transfusion history should be considered in transplantation decision-making in patients with myelodysplastic syndrome

Hematologic passport for athletes competing in endurance sports: a feasibility study.

BACKGROUND AND OBJECTIVES: Strategies based on the use of upper thresholds of hemoglobin or hematocrit to detect blood doping in endurance sports have essentially failed to deter this malpractice. With the aim of establishing a more effective strategy, we analyzed the biological variations of hematologic parameters in professional athletes and investigated the possibility of defining subject-specific reference ranges that could distinguish between physiologic and abnormal variability. DESIGN AND METHODS: Hemoglobin concentration, hematocrit, reticulocyte count, serum ferritin and soluble transferrin receptor levels were sequentially evaluated in 923 professional football players. Using the analysis of variance we tested the effect of age, ethnicity, exercise modalities and training phases on hematologic parameters and then estimated components of variation. The significance of the difference between two measures was obtained from the distribution of the within-subject variance (the so-called reference change). Subject-specific reference ranges were centered around the individual mean value with dispersion based on the 95th percentile of the coefficient of variation distribution. RESULTS: A total of 2,506 hematologic determinations were made. Exercise modalities were found to have important effects on hematologic parameters. Hemoglobin and hematocrit values were higher at the beginning of the competition season, and then declined in well-trained athletes. Aerobic exercise was clearly associated with lower values, suggesting that marginally low hemoglobin and hematocrit values should physiologically be found in endurance sports. At least five determinations were required to define subject-specific reference ranges reliably. Considering athletes showing normal indices of red cell production (i.e., reticulocyte count and soluble transferrin receptor), the 95th percentile of the coefficient of variation distribution was lower than 5\% for both hemoglobin and hematocrit. Increases exceeding 10\% in these latter parameters should to be considered abnormal. Score systems capable of efficiently detecting non-physiologic increases in red cell production were developed. INTERPRETATION AND CONCLUSIONS: Using proper sequential determinations of hematologic variables subject-specific reference ranges can be defined for hemoglobin and hematocrit. Thus, the hematologic passport is feasible and might be employed to exclude athletes with non-physiologic increases in hemoglobin and hematocrit from competitions. The hematologic passport should be used within a global strategy to deter blood doping

Type 1 diabetes among sardinian children is increasing: the Sardinian diabetes register for children aged 0-14 years (1989-1999)

OBJECTIVE. The Sardinian type 1 diabetes register represented the basis to determine the most recent trends and the age distribution of type 1 diabetes incidence among Sardinians <15 years of age during 1989–1999. Part of the data (1989–1998) has been already published by the EURODIAB Group with a lower completeness of ascertainment (87%). The geographical distribution of type 1 diabetes risk was also investigated. RESEARCH DESIGN AND METHODS. The new cases of type 1 diabetes in children aged 0–14 years in Sardinia were prospectively registered from 1989 to 1999 according to the EURODIAB ACE criteria. The completeness of ascertainment calculated applying the capture-recapture method was 91%. Standardized incidence rates and 95% CI were calculated assuming the Poisson distribution. Trend of type 1 diabetes incidence was analyzed using the Poisson regression model. Maps of the geographical distribution of type 1 diabetes risk for the whole time period and separately for 1989–1994 and 1995–1999 were produced applying a Bayesian method. RESULTS. A total of 1,214 type 1 diabetic patients were registered yielding to an overall age- and sex-standardized incidence rate of 38.8/100,000 (95% CI 36.7– 41.1). There was a male excess with an overall male-to-female ratio of 1.4 (1.3–1.8). The increase of incidence during the 11 years analyzed was statistically significant (P= 0.002) with a yearly increasing rate of 2.8% (1.0–4.7). No evidence of an effect of age and sex on this trend has been found. The geographical distribution of type 1 diabetes relative risk (RR) showed that the highest risk areas are located in the southern and central-eastern part of the island and the lowest risk in the northeastern part, even if most of these differences were not statistically significant. This geographical distribution seemed to remain mainly the same between 1989–1994 and 1995–1999. CONCLUSIONS. The homogeneity of diabetes risk and the increase of incidence over the age-groups in the Sardinian population stress the role of an environmental factor uniformly distributed among the genetically high-risk Sardinians