Alessandra Romano
University of Catania
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Publication
Featured researches published by Alessandra Romano.
Journal of Clinical Oncology | 2011
Antonio Palumbo; Michele Cavo; Sara Bringhen; Elena Zamagni; Alessandra Romano; Francesca Patriarca; Davide Rossi; Fabiana Gentilini; Claudia Crippa; Monica Galli; Chiara Nozzoli; Roberto Ria; Roberto Marasca; Vittorio Montefusco; Luca Baldini; Francesca Elice; Vincenzo Callea; Stefano Pulini; Angelo Michele Carella; Renato Zambello; Giulia Benevolo; Valeria Magarotto; Paola Tacchetti; Norbert Pescosta; Claudia Cellini; Claudia Polloni; Andrea Evangelista; Tommaso Caravita; Fortunato Morabito; Massimo Offidani
PURPOSE In patients with myeloma, thalidomide significantly improves outcomes but increases the risk of thromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin (ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens. PATIENTS AND METHODS A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were randomly assigned to receive ASA (100 mg/d), WAR (1.25 mg/d), or LMWH (enoxaparin 40 mg/d). A composite primary end point included serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment. RESULTS Of 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascular events, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WAR group, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were +1.3% (95% CI, -3.0% to 5.7%; P = .544) in the ASA group and +3.2% (95% CI, -1.5% to 7.8%; P = .183) in the WAR group. The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%) bleeding episodes were recorded. CONCLUSION In patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similar efficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deaths compared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.
Blood | 2011
Alessandra Larocca; Pierre W. Wijermans; Federica Cavallo; Davide Rossi; Ron Schaafsma; Mariella Genuardi; Alessandra Romano; Anna Marina Liberati; Agostina Siniscalchi; Maria Teresa Petrucci; Chiara Nozzoli; Francesca Patriarca; Massimo Offidani; Roberto Ria; Paola Omedè; Benedetto Bruno; Roberto Passera; Pellegrino Musto; Mario Boccadoro; Pieter Sonneveld; Antonio Palumbo
Complete response (CR) was an uncommon event in elderly myeloma patients until novel agents were combined with standard oral melphalan-prednisone. This analysis assesses the impact of treatment response on progression-free survival (PFS) and overall survival (OS). We retrospectively analyzed 1175 newly diagnosed myeloma patients, enrolled in 3 multicenter trials, treated with melphalan-prednisone alone (n = 332), melphalan-prednisone-thalidomide (n = 332), melphalan-prednisone-bortezomib (n = 257), or melphalan-prednisone-bortezomib-thalidomide (n = 254). After a median follow-up of 29 months, the 3-year PFS and OS were 67% and 27% (hazard ratio = 0.16; P < .001), and 91% and 70% (hazard ratio = 0.15; P < .001) in patients who obtained CR and in those who achieved very good partial response, respectively. Similar results were observed in patients older than 75 years. Multivariate analysis confirmed that the achievement of CR was an independent predictor of longer PFS and OS, regardless of age, International Staging System stage, and treatment. These findings highlight a significant association between the achievement of CR and long-term outcome, and support the use of novel agents to achieve maximal response in elderly patients, including those more than 75 years. This trial was registered at www.clinicaltrials.gov as #NCT00232934, #ISRCTN 90692740, and #NCT01063179.
Mammalian Genome | 1996
T. DiPalma; M. Tucci; G. Russo; D. Maglione; C. T. Lago; Alessandra Romano; Salvatore Saccone; G. Delia Valle; L. De Gregorio; Tommaso A. Dragani; G. Viglietto; M. G. Persico
Placenta growth factor (P1GF) and vascular endothelial growth factor (VEGF) are angiogenic factors containing the 8-cysteine motif of platelet-derived growth factor (PDGF). Both P1GF and VEGF are mitogens for endothelial cells in vitro and promote neoangiogenesis in vivo. In addition, PIGF strongly potentiates the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. We have now isolated the cDNA coding for mouse Plgf by screening a mouse heart cDNA library with the human P1GF sequence as probe. The human P1GF protein has two forms, P1GF-1 and P1GF-2, that arise from alternative splicing of a single gene mapping on Chromosome (Chr) 14; the isolated mouse Plgf cDNA encodes the longer of these two forms (PIGF-2). We show that the mouse Plgf- 2 mRNA is the only transcript present in the normal tissues analyzed. Mouse Plgf-2 is a 158-amino-acid-long protein that shows 78% similarity (65% identity) to the human P1GF-2. Computer analysis reveals a putative signal peptide and three probable N-glycosylation sites, two of which are also conserved in human P1GF. The mouse Plgf gene was isolated and characterized; the gene is encoded by 7 exons spanning a 13-kb DNA interval. Finally, we have mapped the mouse Plgf gene to Chr 12, one cM from D12Mit5, and the human P1GF gene to 14q24, using both FISH and genetic crosses.
BioMed Research International | 2014
Alessandra Romano; Concetta Conticello; Maide Cavalli; Calogero Vetro; Alessia La Fauci; Nunziatina Parrinello; Francesco Di Raimondo
Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.
British Journal of Haematology | 2015
Alessandra Romano; Nunziatina Parrinello; Calogero Vetro; Stefano Forte; Annalisa Chiarenza; Amalia Figuera; Giovanna Motta; Giuseppe Palumbo; Massimo Ippolito; Ugo Consoli; Francesco Di Raimondo
In the attempt to find a peripheral blood biological marker that could mirror the dysregulated microenvironment of Hodgkin Lymphoma (HL), we analysed the amount of myeloid‐derived suppressor cells (MDSC), including the three main sub‐types (monocytic, granulocytic and CD34 + fraction). The absolute MDSC count was investigated in 60 consecutive newly diagnosed HL patients and correlated with clinical variables at diagnosis and outcome. Patients received standard‐of‐care chemotherapy with the exception of interim fluorodeoxyglucose positron emission tomography (PET‐2)‐positive patients, who were switched early to a salvage regimen. All MDSC subsets were increased in HL patients compared to normal subjects (P < 0·0001) and were higher in non‐responders. However, a strong prognostic significance was limited to immature (CD34+) MDSC. A cut‐off level of 0·0045 × 109/l for CD34+MDSC resulted in 89% (95% confidence interval [CI] 52–99%) sensitivity and 92% (95% CI 81–98%) specificity. The positive predictive value to predict progression‐free survival was 0·90 for PET‐2 and 0·98 for CD34+MDSC count; the negative predictive value was 0·57 for PET‐2 and 0·73 for CD34+MDSC. PFS was significantly shorter in patients with more than 0·0045 × 109 CD34+MDSC cells/l at diagnosis and/or PET‐2 positivity (P < 0·0001). In conclusion, all circulating MDSC subsets are increased in HL; CD34+MDSC predict short PFS, similarly to PET‐2 but with the advantage of being available at diagnosis.
Leukemia Research | 2010
Vincenza Barresi; Giuseppe A. Palumbo; Nicolò Musso; Carla Consoli; Carmela Capizzi; Carmela Rita Meli; Alessandra Romano; Francesco Di Raimondo; D. F. Condorelli
By conventional metaphase and SNP array cytogenetics we serially studied a patient affected by high-risk myelodysplastic syndrome (MDS), documenting the conversion from partial trisomy 8q to trisomy 8 and partial tetrasomy 8q during progression to acute myeloid leukemia (AML). Moreover, the serial application of high resolution genomic array analysis at different disease stages allowed the description of cryptic abnormalities and the demonstration of their enrichment in the AML phase. In particular the detection and quantification of a copy-neutral loss of heterozygosity region located in chromosome 11q guided the search for point mutations in the CBL gene, thus allowing the escription of the novel missense mutation K382E and the demonstration of its selection during progression to secondary AML.
Haematologica | 2014
Manuela Gambella; Alberto Rocci; Roberto Passera; Paola Omedè; Claudia Crippa; Paolo Corradini; Alessandra Romano; Davide Rossi; Marco Ladetto; Mario Boccadoro; Antonio Palumbo
Multiple myeloma (MM) is a hematologic tumor characterized by accumulation of monoclonal plasma cells (PCs) in the bone marrow (BM) producing antigen-specific immunoglobulins. The transcription factor X box binding protein 1 (XBP1), the interferon regulatory factor 4 (IRF4) and the transcriptional
PLOS ONE | 2014
Cesarina Giallongo; Nunziatina Parrinello; Daniele Tibullo; Piera La Cava; Alessandra Romano; Annalisa Chiarenza; Ignazio Barbagallo; Giuseppe A. Palumbo; Fabio Stagno; Paolo Vigneri; Francesco Di Raimondo
Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs), able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML) patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1) that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs) we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.
Genes, Chromosomes and Cancer | 2010
Vincenza Barresi; Alessandra Romano; Nicolò Musso; Carmela Capizzi; Carla Consoli; Maria Paola Martelli; Giuseppe A. Palumbo; Francesco Di Raimondo; D. F. Condorelli
We analyzed, by the latest high‐resolution SNP arrays, 19 Normal Karyotype (NK)‐AML patients at diagnosis (Dx) and remission (R) phases, to determine the number of tumor‐associated copy number abnormalities (CNAs) and copy neutral‐loss of heterozygosity (CN‐LOH) regions per patient and to identify possible recurring genomic abnormalities. The number of tumor‐associated CNAs was determined after comparison of matched Dx/R samples using stringent conditions able to reduce the number of false positive CNAs. With the exception of a single outlier case, a low number of CNAs per patient was detected (median value of 1 somatic loss or gain per patient). However, a high prevalence of CNAs (60–70% of the patients showed at least one tumor‐associated gain or loss) and few recurring CNAs were observed, thus providing new hints towards identification of cooperating mutations. An extensive search of all tumor‐associated CN‐LOH regions >1 Mb revealed only three broad regions (terminal 12Mb of 22q, terminal 27Mb of 1p and the whole chromosome 21) in three patients out of 19 (16%). CN‐LOH of the whole chromosome 21 was responsible for homozygosity of a missense mutation (R80C) of RUNX1/AML1. Our study suggests that a relative submicroscopic copy number stability NK‐AML genomes is associated with low recurrence of specific CNAs and CN‐LOH in NK‐AML patient population. Sequencing of candidate genes in the identified CNAs and CN‐LOH regions should be considered a priority in the search of novel driver mutations of AML.
Immunotherapy | 2013
Alessandra Romano; Concetta Conticello; Francesco Di Raimondo
Management of multiple myeloma (MM) has been drastically changed in the last 10 years thanks to the introduction of novel agents, which, combined with the backbone of classical chemotherapy, have led to a significant improvement in disease control. Bortezomib is the first reversible proteasome inhibitor approved for the treatment of MM, with wide synergism in vitro and in vivo with a plethora of drugs active for MM. In patients eligible for autologous stem cell transplantation (ASCT), the achievement of complete response or very good partial response before ASCT is associated with prolonged progression-free and overall survival. Thus, the goal of induction regimens should include, at least for younger patients, a continued improvement of the quality and depth of the achieved response. This article is focused on reviewing the major efforts in frontline therapy for MM, including bortezomib-containing induction regimens in patients either eligible or ineligible for ASCT.