Showing papers by "Giovanni Barosi published in 2011"
TL;DR: A review of critical concepts and recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first- and second-line therapy, and therapy for special issues are presented.
Abstract: We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, fi ...
731 citations
TL;DR: The MPN-SAF is a comprehensive and reliable instrument that is available in multiple languages to evaluate symptoms associated with all types of MPNs in clinical trials globally.
282 citations
TL;DR: EZH2 mutations are independently associated with shorter survival in patients with PMF and in multivariate analysis, survival of PMF patients was predicted by IPSS high-risk category, a < 25% JAK2V617F allele burden, and EZh2 mutation status.
244 citations
TL;DR: It is indicated that blood levels of high sensitivity C-reactive protein and petraxin 3 independently and in opposite ways modulate the intrinsic risk of cardiovascular events in patients with myeloproliferative disorders.
Abstract: We tested the hypothesis that levels of pentraxin high sensitivity C-reactive protein and pentraxin 3 might be correlated with cardiovascular complications in patients with essential thrombocythemia and polycythemia vera. High sensitivity C-reactive protein and pentraxin 3 were measured in 244 consecutive essential thrombocythemia and polycythemia vera patients in whom, after a median follow up of 5.3 years (range 0-24), 68 cardiovascular events were diagnosed. The highest C-reactive protein tertile was compared with the lowest (>3 vs. <1 mg/L) and correlated with age (P=0.001), phenotype (polycythemia vera vs. essential thrombocythemia, P=0.006), cardiovascular risk factors (P=0.012) and JAK2V617F allele burden greater than 50% (P=0.003). Major thrombosis rate was higher in the highest C-reactive protein tertile (P=0.01) and lower at the highest pentraxin 3 levels (P=0.045). These associations remained significant in multivariate analyses and indicate that blood levels of high sensitivity C-reactive protein and petraxin 3 independently and in opposite ways modulate the intrinsic risk of cardiovascular events in patients with myeloproliferative disorders.
160 citations
TL;DR: Results provide proof-of-concept that targeting mTOR pathway in myelofibrosis may be clinically relevant, and identify possible biomarkers associated with response.
145 citations
Imperial College London1, University of Pavia2, University of Barcelona3, University of Ulm4, University of Toronto5, Guy's and St Thomas' NHS Foundation Trust6, Icahn School of Medicine at Mount Sinai7, University of Paris8, Mayo Clinic9, Queen's University Belfast10, Institut Gustave Roussy11, Cornell University12, University of Turin13, University of Florence14, University of Texas MD Anderson Cancer Center15
TL;DR: A structured expert-panel consensus panel process is used to define RBC-transfusion-dependence and -independence or improvement and it is suggested these definitions may prove useful to persons studying or treating these diseases.
77 citations
TL;DR: The term “biosimilars” (“follow-on biologics” in the USA) has been used by the European Medicines Agency (EMA) to describe officially-approved subsequent versions of innovator biotechnological products made by a different competitor after the patent and exclusivity rights have expired.
Abstract: The term “biosimilars” (“follow-on biologics” in the USA) has been used by the European Medicines Agency (EMA) to describe officially-approved subsequent versions of innovator biotechnological products made by a different competitor after the patent and exclusivity rights have expired.1 Biosimilars pose a problem to the clinician who is bound to require guidance on how best to capitalize on these new pharmacological opportunities. In its mandate to promote the best hematologic care, the Italian Society of Hematology (SIE) and the affiliate societies SIES (Societa Italiana di Ematologia Sperimentale) and GITMO (Gruppo Italiano Trapianto di Midollo Osseo) convened an expert panel to produce a position paper on the two marketed biosimilars in hematology, i.e. epoetin and filgrastim. The panel of 8 experts was selected according to the conceptual framework elements of the NIH Consensus Development Program.2 Panel bias was minimized by eliminating from consideration strong advocates for or against the use of biosimilars. Each panel member was asked to disclose any tie he or she may have had with pharmaceutical companies manufacturing the drugs considered in the paper in the last five years. The project was conducted independently from any pharmaceutical company which sold either conventional drugs or biosimilars.
62 citations
TL;DR: Profound differences in megakaryocyte morphology and proplatelet formation distinguish PMF, both fibrotic and prefibrotic, from ET and PV, and MPNs are associated with high megakARYocyte proliferative potential.
Abstract: Background
Ph-negative myeloproliferative neoplasms (MPNs) are clonal disorders that include primary myelofibrosis (PMF), polycythemia vera (PV) and essential thrombocythemia (ET). Although the pathogenesis of MPNs is still incompletely understood, an involvement of the megakaryocyte lineage is a distinctive feature.
51 citations
TL;DR: Examination of TGFβ1 levels in Philadelphia-negative myeloproliferative diseases found that patients with primary myelofibrosis have higher peripheral blood plasma levels of both bioactive and total TGF β1 than healthy controls, with a balance bioactive/total T GFβ1 in favour of the latter.
29 citations
TL;DR: This data indicates that once the BRCA1/BRCA2 gene is removed, the B cell reprograming strategy is likely to be a viable alternative to chemotherapy and may be helpful in the selection of patients for B-cell transplantation.
Abstract: LBA6501 Background: MF, a myeloproliferative neoplasm characterized by dysregulation of the JAK pathway, is associated with splenomegaly, constitutional symptoms and reduced lifespan. Ruxolitinib is a potent and selective JAK1 and JAK2 inhibitor. Methods: COMFORT-II, a randomized (2:1) phase III study, compared the efficacy and safety of ruxolitinib PO BID with BAT (other agents or no therapy) in adults with intermediate-2 or high-risk (Cervantes et al, Blood 2009) PMF, PPV-MF or PET-MF and palpable splenomegaly. The primary endpoint was the proportion of patients (pts), stratified by baseline risk category, achieving ≥ 35% reduction in spleen volume at week (wk) 48 determined by MRI or CT. The key secondary endpoint was the proportion achieving ≥ 35% reduction in spleen volume at wk 24. Results: 219 pts were randomized: 146 to ruxolitinib and 73 to BAT. Both arms included 49% high- and 51% intermediate-2 risk pts. The wk 48 response rate was 28.5% vs 0% (ruxolitinib vs BAT, P < .0001). The wk 24 response...
29 citations
TL;DR: Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors.
Abstract: Introduction: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated myelofibrosis has provided a new target for innovative treatment strategies. Areas covered: This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated myelofibrosis from early 2000 to December 2010. Expert opinion: Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported...
TL;DR: Human mesenchymal stromal cells (MSCs) expanded in vitro for cell therapy approaches need to be carefully investigated for genetic stability, by employing both molecular and conventional karyotyping.
Abstract: Human mesenchymal stromal cells (MSCs) expanded in vitro for cell therapy approaches need to be carefully investigated for genetic stability, by employing both molecular and conventional karyotyping. Reliability of cytogenetic analysis may be hampered in some MSC samples by the difficulty of obtaining an adequate number of metaphases. In an attempt to overcome this problem, a methodology apt to evaluate the cell-cycle structure on synchronous MSCs was optimised. Results obtained in five independent experiments by comparing cell-cycle analysis of synchronous and asynchronous MSC populations evaluated at early and late culture passages documented that in synchronous MSCs, 30% of cells entered G2/M phase after about 27–28 h of culture, while in asynchronous MSCs only 8% of cells in G2/M phase could be observed at the same time point. Cytogenetic analysis on synchronous MSCs allowed us to obtain 20–25 valuable metaphases/slide, whereas only 0–4 metaphases/slide were detectable in asynchronous preparations. J. Cell. Biochem. 112: 1817–1821, 2011. © 2011 Wiley-Liss, Inc.
TL;DR: Ruxolitinib was shown to be more effective than BAT at reducing spleen volume in all patient subgroups regardless of gender, age, mutation status, IPSS risk category, baseline spleen size, MF subtype, or ruxolit inib starting dose.
Heidelberg University1, King's College London2, Uppsala University3, Imperial College London4, University of Bologna5, University of Upper Alsace6, University of Münster7, Cardiff University8, University of Southampton9, Radboud University Nijmegen10, University of Ulm11, University of Paris12, University of Würzburg13, Medical University of Vienna14, Goethe University Frankfurt15, University of Basel16, University of Cologne17, Ludwig Maximilian University of Munich18, University of Jena19, University of Zagreb20, Karolinska Institutet21, Leipzig University22, VU University Amsterdam23, Autonomous University of Barcelona24, University of Düsseldorf25
TL;DR: The European LeukemiaNet has improved leukemia research and management across Europe and has led to funding by the European Commission as a network of excellence.
Abstract: The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.
TL;DR: Givinostat confirms to be active in PV through the control of myeloproliferation and of some specific clinical needs, such as severe itching, which is well tolerated and about 50% of patients resistant to HU monotherapy achieved an overall ELN response (PR or CR).
TL;DR: The first US prospective phase II study of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary myelofibrosis or MF secondary to essential thrombocythemia (ET-MF) or polycythemia vera (PV-MF), designed by the Myeloproliferative Disorder-Research Consortium, is designed.
Rosalind Franklin University of Medicine and Science1, Mayo Clinic2, VU University Medical Center3, Vanderbilt University Medical Center4, Erasmus University Rotterdam5, Loyola University Medical Center6, Hospital Universitario La Paz7, University of Ulm8, University Hospital of Basel9, University of Puerto Rico10, University of Barcelona11, University of Florence12, University of Pavia13
TL;DR: The utility of an average total symptom score (TSS) from the most pertinent and representative MPN symptoms for purposes of assessing the burden of symptoms in MPN pts, and subsequent tracking in response to therapy is assessed.
TL;DR: Genotyped at diagnosis 370 pts with primary MF (PMF) and 148 with post-polycythemia vera/essential thrombocythemia MF (PPV/PET-MF) for mutations of EZH2 and ASXL1 to identify pts with very high-risk disease, based on intrinsic characteristics of the underlying disease.
TL;DR: Additional post hoc analyses from the COMFORT-II study further support that ruxolitinib improves overall HRQoL and MF symptoms compared with overall BAT, and assesses changes from baseline in HRQeL andMF symptom scores, including the EORTC subscales, LymS, and FACT total scores, which incorporate well-being and/or symptom subscales.
TL;DR: Recent data is cited illustrating the complexity of cell types comprising the bone marrow micro-environment and showing that at least some of the cells responsible for bone marrow fibrosis are clonal and genetically related to the MPN-clone.
TL;DR: The Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) as discussed by the authors is a research center for the study of myelofibrosis.
Abstract: 1Biotechnology Laboratory, Fondazione IRCCS Policlinico San Matteo,Pavia, Italy, 2Unit of Clinical Epidemiology and Centre for the Study of Myelofibrosis, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 3Immunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 4Unit of Haematopancreatic Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
TL;DR: Overall, the data indicate that MF adversely effects physical and emotional functioning and QOL, and justifies the search for MF therapies that seek to improve symptoms.
Abstract: 6610 Background: The symptomatic burden in patients (pts) with myeloproliferative neoplasm myelofibrosis (MF) is significant and being evaluated as a major target of experimental therapies. We cond...
TL;DR: The BM picture of preMF identifies a group of patients with PMF associated with a very indolent hematologic phenotype, female dominance and very young age at presentation characterized by high incidence of splanchnic vein thrombosis.
TL;DR: Ruxolitinib is currently the only drug to have completed phase 3 studies for the treatment of MF and has garnered a substantial number of requests for access through the individual supply program.