A total of 187 consecutive patients with essential thrombocythemia (ET) were diagnosed and followed by our Hematology Department in the period October 1980-November 1994. The overall follow-up was 773 patient-years. Thrombosis-free survival and overall survival were calculated for the whole cohort; the same parameters were then calculated after arbitrary division of the cohort into two groups, according to the median age at diagnosis (55 years). Fifty percent of the patients had at least one thrombotic episode within 9 years after diagnosis. The thrombosis-free survival curves calculated for patients younger or older than 55 years at diagnosis were comparable. About 85% of the patients were alive 10 years after diagnosis. The survival curves for patients younger and older than 55 years at diagnosis were not significantly different in the observation period, and the observed mortality (seven patients) among patients younger than 55 years at diagnosis was significantly higher than expected (1.68 cases). The relative risk of death was four times greater (SMR = 4.17, 95% C.I. 1.6-8.6, p<0.01) than for healthy, age-matched people living in the same area. Age at diagnosis, smoking, sex, hypercholesterolemia, peak number of platelets, hypertension, and diabetes were not significant prognostic cardiovascular risk factors in our cohort. In conclusion, our data show that ET has to be considered a serious disease that significantly decreases both quality of life (expected life without thrombosis) and life expectancy for younger patients.
SummaryWe previously reported a 60% erythroid response rate with recombinant erythropoietin + 13-cis retinoic acid + dihydroxylated vitamin D3 in 63 elderly myelodysplastic patients (median age 75 years) with unfavourable features for response to erythropoietin alone [70% transfusion-dependent, 35% refractory anaemia with ring sideroblasts/refractory anaemia with excess of blasts type 1 (RAEB1), 70% with International Prognostic Scoring System (IPSS) Intermediate-1 or -2]. This report updates that case study at a 7-year follow-up, and compared the impact on overall survival of erythroid response to known prognostic factors. The erythroid response duration (median 17 months; 22 in non-RAEB patients, with 20% patients in response after 6 years of therapy) was longer than in most studies with erythropoietin alone. Overall survival (median 55 months in non-RAEB, 15 in RAEB1 patients) was negatively affected by RAEB1 diagnosis, IPSS and WPSS intermediate scores and transfusion-dependence. In the multivariate analysis, erythroid response maintained an independent positive impact on survival, particularly in non-RAEB patients in the first 3 years from diagnosis (90% survival compared to 50% of non-responders). In conclusion, the long-term follow-up confirmed the achievement, by our combined treatment, of fairly long-lasting erythroid response in the majority of MDS patients with unfavourable prognostic features for response to erythropoietin: this translated in a survival benefit that was independent from other prognostic features.
Procoagulant activity (PCA) of peripheral mononuclear cells (PMC) was evaluated in patients with primary thrombocythemia (PT, group A), polycythemia vera (PV), idiopathic myelofibrosis (IM) and myelodysplastic syndromes (group B), and in 15 healthy subjects as control group. PCA of PMC was assayed under basal conditions and after agonist-induced stimulation: bacterial lipopolysaccharide, glycosylated granu-locyte-macrophage colony-stimulating factor, recombinant α-interferon. PCA was similar in the control group and group A when no stimulation was used, while PCA was found significantly higher in group B patients in the same conditions. In group A patients and in the control group, but not in group B patients, a lower PCA expression was found when PMC were simultaneously coincubated with LPS and α-interferon with respect to LPS incubation alone.
Growth advantage of chronic myeloid leukemia CFU-GM in vitro: survival to growth factor deprivation, possibly related to autocrine stimulation, is a more common feature than hypersensitivity to GM-CSF/IL3 and is efficiently counteracted by retinoids ± ␣-interferon D Ferrero, C Foli, F Giaretta, C Argentino, C Rus and A Pileri Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S Giovanni Battista, Torino, Italy Bcr/abl fusion gene, in experimental models, induces survival to growth factor deprivation and hypersensitivity to IL3. However, conflicting data were reported about chronic myeloid leukemia (CML) progenitors. We investigated the responsiveness of purified CML CFU-GM to GM-CSF/IL3 and their survival to growth factor deprivation. CFU-GM hypersensitivity to IL3 and/or GM-CSF was found in 3/11 CML cases only. CML CFU-GM survived well in stroma-free 'mass' culture (5 × 10 4 cells/ml) without cytokine addition, up to day 11, average recovery being around 95% in medium + 10% fetal bovine serum and 67-81% in serum-free medium. Conversely, normal progenitors declined steadily, particularly after extensive purification (18 ± 10% recovery at the 7th day), and in serum-free medium (4 ± 6% recovery). By contrast, normal and CML CFU-GM declined in a similar way in limiting dilution cultures (1-10 cells/50 l). We also investigated the effects of retinoic acid and ␣-interferon on CFU-GM survival. Both all-trans-and 13-cis retinoic acid, particularly in combination with ␣-interferon, reduced CML CFU-GM recovery down to normal progenitors' values. In conclusion, hypersensitivity to CSFs is rare in CML, whereas resistance to growth factor deprivation has been confirmed in mass, but not in limiting, dilution cultures. Both stereoisomers of retinoic acid, at therapeutic concentrations and in combination with ␣-interferon, can overcome the survival advantage of CML progenitors. Leukemia (2001) 15, 422-429.
was performed 8 days after coupling (Fig. 2 in the online Data Supplement). However, on interpolation of data points from the calibration curve, the trend was reversed such that the highest signal was observed for experiment 3 and the lowest for experiment 1.In parallel studies, antigen-conjugated beads stored at 4°C gave consistent fluorescent emission within a period of 1 month, whereas antibody-conjugated beads showed diminished fluorescent emission (data not shown).We identified two limitations of this methodology: The inherent instability of antibody-coupled beads and the occurrence of data points from test samples outside the linear portion of the semilogarithmic calibration curve. To resolve the latter issue, serum samples exhibiting fluorescent output within the plateau of the trendline should be reassayed after further dilution. Problems with long-term stability of protein-conjugated bead sets were evident when the beads were stored at 4°C. On the Luminex platform, antibody-conjugated beads were viable for approximately 3 weeks. Antigen-conjugated beads exhibited slightly greater longevity, although decoding of the fluorescent signatures was problematic after storage at 4°C beyond 1 month. The constituents of the storage buffer may have a detrimental effect on the fluorescent dyes within the microspheres.The reversal of the signal output profile suggests that antibody-bound beads were more liable to degradation than antigen-coupled bead sets within the same timescale. The more elaborate structural complexity of antibodies compared with antigens may account for the greater instability of the former. Rapid freezing and lyophilization were procedures explored as alternative methods to prolong the shelf-life of protein-coupled beads, and both approaches appeared to be feasible (17 ). This provides the possibility of developing calibration bead sets as reference materials, thus enabling Luminex assay standardization.This study illustrated the complexity of quantifying target analytes within antigen arrays. Production of purified antibodies is laborious and expensive. Methods that can be used for antibody purification, e.g., affinity chromatography, could theoretically be used to obtain material comparable to the target analyte of an antigen array. However, consistent antibody purity is paramount for quantification.Although this approach has broad application for the comparison of any IgG, it will not measure absolute concentrations of target analyte. This is largely because of the presence of factors (e.g., soluble receptors, heterophilic antibodies, serum binding proteins, hemoglobin, and lipids) in sera that can interfere with antibody-based immunoassays (18 ). Nonetheless, this method has reduced intraassay variability and enables interassay comparisons for a wide range of antigen arrays.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.