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Passamonti F.,University Hospital Ospedale Of Circolo ndazione Macchi
Leukemia | Year: 2012

My diagnostic approach in case of isolated erythrocytosis is based on the visit and the interview of patients, and on checking the causes of secondary erythrocytosis. If causes of secondary erythrocytosis are not evident and serum erythropoietin level is low-normal, I study JAK2 mutations. In the case of a patient with erythrocytosis and other signs of myeloproliferation, such as leukocytosis, thrombocytosis or splenomegaly, the diagnosis of polycythemia vera (PV) is likely, and I test serum erythropoietin and JAK2 mutations first. I stratify patients at diagnosis of PV according to age and history of thrombosis. I start hydroxyurea for patients who are at a high risk of thrombosis (that is, with one or two risk factors), while I continue only phlebotomy in other cases. All PV patients, if not contraindicated, receive aspirin. I follow up patients monthly until normalization of their blood cell counts or splenomegaly, and afterwards every 2 months with visit, cell blood count and blood smear evaluation. After diagnosis, I perform bone marrow biopsy only in the case of clinical signs of disease evolution. © 2012 Macmillan Publishers Limited All rights reserved.

Vernocchi A.,Laboratory Medicine IRCCS MultiMedica | Longhi E.,Laboratory Medicine IRCCS MultiMedica | Lippi G.,Laboratory of Clinical Chemistry and Hematology | Gelsumini S.,University Hospital Ospedale Of Circolo ndazione Macchi
Journal of Medical Biochemistry | Year: 2016

Background: Identification, quantification and typing of MProteins (MP) play an important role in the diagnosis, classification and monitoring of monoclonal gammopathies both of malignant origin (eg. Multiple Myeloma) and of unknown origin. Previous evidence attests that MGUS (Monoclonal Gammopathy of Undetermined Significance) detected by agarose gel electrophoresis has a prevalence of 3.2% in the general population. Therefore, our study aimed to verify this data by means of capillary zone electrophoresis (CZE). Methods: CZE was performed to evaluate the prevalence of M-Protein (MP) in 44.474 consecutive outpatients of all ages with a prescription for serum protein electrophoresis over a 2-year period (2008 and 2009). All MPs that were identified were then typed by immunofixation electro pho - resis on agarose gel (IFE). Results: In subjects aged over 50 (23.408, i.e., 52.6% of the whole cohort) MP ≤30 g/L (MGUS) was identified in 6.0% of cases, with a frequency nearly double than that previously reported. The population was then divided into ten-year age groups: the 71-80 age group had the highest percentage of MP (29%), followed by 61-70 (27%), 51-60 (18%), 81-90 (12%), 41-50 (8%), 31-40 (3%), >90 (2%) and <30 (1%). The frequency of MP types (IFE) was the same in each age group, with IgG Kappa being the most represented class. Conclusions: According to the high MGUS prevalence observed in this study, these results may be useful especially for general practitioners, because the identification even of small MP (analytical sensitivity: 0.5 g/L) may help optimize clinical management. © by Silvia Gelsumini 2016.

Passamonti F.,University Hospital Ospedale Of Circolo ndazione Macchi
Blood | Year: 2012

Polycythemia vera (PV) is a clonal disorder characterized by unwarranted production of red blood cells. In the majority of cases, PV is driven by oncogenic mutations that constitutively activate the JAK-STAT signal transduction pathway, such as JAK2 V617F, or exon 12 mutations or LNK mutations. Diagnosis of PV is based on the WHO criteria. Diagnosis of post-PV myelofibrosis is established according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria. Different clinical presentations of PV are discussed. Prognostication of PV is tailored to the most frequent complication during follow-up, namely, thrombosis. Age older than 60 years and prior history of thrombosis are the 2 main risk factors for disease stratification. Correlations are emerging between leukocytosis, JAK2(V617F) mutation, BM fibrosis, and different outcomes of PV, which need to be confirmed in prospective studies. In my practice, hydroxyurea is still the "gold standard" when cytoreduction is needed, even though pegylated IFN-alfa-2a and ruxolitinib might be useful in particular settings. Results of phase 1 or 2 studies concerning these latter agents should however be confirmed by the ongoing randomized phase 3 clinical trials. In this paper, I discuss the main problems encountered in daily clinical practice with PV patients regarding diagnosis, prognostication, and therapy. © 2012 by The American Society of Hematology.

Passamonti F.,University Hospital Ospedale Of Circolo ndazione Macchi
Blood | Year: 2014

In this issue of Blood, Cheah et al provide long-term data on the use of imatinib to treat patients with eosinophilia and myeloid neoplasms carrying the PDGFRB fusion gene, which is a very rare condition in medicine. © 2014 by The American Society of Hematology.

Barbui T.,Ospedali Riuniti di Bergamo | Finazzi G.,Ospedali Riuniti di Bergamo | Carobbio A.,Ospedali Riuniti di Bergamo | Thiele J.,University of Cologne | And 13 more authors.
Blood | Year: 2012

Accurate prediction of thrombosis in essential thrombocythemia (ET) provides the platform for prospective studies exploring preventive measures. Current risk stratification for thrombosis in ET is 2-tiered and considers low- and high-risk categories based on the respective absence or presence of either age > 60 years or history of thrombosis. In an international study of 891 patients with World Health Organization (WHO) - defined ET, we identified additional independent risk factors including cardiovascular risk factors and JAK2 V617F. Accordingly, we assigned risk scores based on multivariable analysis-derived hazard ratios (HRs) to age > 60 years (HR = 1.5; 1 point), thrombosis history (HR = 1.9; 2 points), cardiovascular risk factors (HR = 1.6; 1 point), and JAK2 V617F (HR = 2.0; 2 points) and subsequently devised a 3-tiered prognostic model (low-risk = < 2 points; intermediate-risk = 2 points; and high-risk = > 2 points) using a training set of 535 patients and validated the results in the remaining cohort (n = 356; internal validation set) and in an external validation set (n = 329). Considering all 3 cohorts (n = 1220), the 3-tiered new prognostic model (low-risk n = 474 vs intermediate-risk n = 471 vs high-risk n = 275), with a respective thrombosis risk of 1.03% of patients/y versus 2.35% of patients/y versus 3.56% of patients/y, outperformed the 2-tiered (low-risk 0.95% of patients/y vs high-risk 2.86% of patients/y) conventional risk stratification in predicting future vascular events. © 2012 by The American Society of Hematology.

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