45 results on '"Morabito F."'
Search Results
2. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study
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Marzona, I., Avanzini, F., Lucisano, G., Tettamanti, M., Baviera, M., Nicolucci, A., Roncaglioni, M. C., Tombesi, M., Tognoni, G., Massa, E., Marrocco, W., Micalella, M., Caimi, V., Longoni, P., Franzosi, M. G., Monesi, L., Pangrazzi, I., Barlera, S., Milani, V., Nicolis, E., Casola, C., Clerici, F., Palumbo, A., Sgaroni, G., Marchioli, R., Silletta, M. G., Pioggiarella, R., Scarano, M., Marfisi, R. M., Flamminio, A., Macino, L., Ferri, B., Pera, C., Polidoro, A., Abbatino, D., Acquati, M., Addorisio, G., Adinolfi, D., Adreani, L., Agistri, M. R., Agneta, A., Agnolio, M. L., Agostini, N., Agostino, G., Airo, A., Alaimo, N., Albano, M., Albano, N., Alecci, G., Alemanno, S., Alexanian, A., Alfarano, M., Alfe, L., Alonzo, N., Alvino, S., Ancora, A., Andiloro, S., Andreatta, E., Angeli, S., Angiari, F., Angilletti, V., Annicchiarico, C., Anzivino, M., Aprea, R., Aprile, A., Aprile, E., Aprile, I., Aprile, L., Armellani, V., Arnetoli, M., Aronica, A., Autiero, V., Bacca, G., Baccalaro, A. M., Bacci, M., Baglio, G., Bagnani, M., Baiano, A., Baldari, A., Ballarini, L., Banchi, G., Bandera, R., Bandini, F., Baratella, M., Barbieri, A., Barbieri Vita, A., Bardi, M., Barlocchi, M., Baron, P., Bartoli, M., Basile, A., Basile, F., Basile, S., Battaggia, A., Battaglia, A., Bau, A., Beconcini, G., Beggio, R., Belfiore, P. A., Belicchi, M., Bellamoli, S., Bellini, C., Bellomo, M., Benetollo, C., Benetti, R., Beretta, E., Bertalero, P., Bertaso, F. G., Bertolani, U., Bettelli, G., Biagiotti, G., Bianchi, S., Bianco, G., Biccari, F., Bigioli, F., Bindi, M., Bisanti, G., Bitetti, E. M., Blasetti, M. P., Blesi, F., Boato, V., Boga, S., Boidi, E., Boldrin, G., Bollati, A., Bolzan, L., Bolzonella, S., Bonardi, P., Bonato, G. B., Bonci, M., Bonfitto, G., Bonincontro, E., Boninsegna, F., Bonissone, D., Bono, L., Bonollo, E., Borghi, M., Borioli, N., Borsatto, M., Bosco, T., Bosisio Pioltelli, M., Botarelli, C., Botassis, S., Bottini, F., Bottos, C., Bova, G., Bova, V., Bozzani, A., Bozzetto, R. M., Braga, V. T., Braglia, M., Bramati, E., Brazzoli, C., Breglia, G., Brescia, A., Briganti, D., Brigato, G., Brocchi, A., Brosio, F. A., Bruni, E., Buscaglia, E., Bussini, M. D., Bussotti, A., Buzzaccarini, F., Buzzatti, A., Caccamo, G., Cacciavillani, C., Caggiano, G., Calciano, F. P., Calderisi, M., Calienno, S., Caltagirone, P., Calzolari, I., Cammisa, M., Campanaro, M., Campanella, G. B., Campese, F., Canali, G., Candiani, D. E. L., Canepa, R., Canini, D., Canino, A., Cantoro, E. A., Capilupi, V., Capotosto, P., Cappelli, B., Capraro, G., Carafa, F. A., Carano, Q., Carcaterra, V., Carriero, D., Carrozzo, G., Cartanese, M., Casalena, M., Casarola, M., Caso, C., Casotto, M., Castaldi, F., Castegnaro, R., Castellani, G., Castri, S., Catalano, E., Catinello, N., Caturano, G., Cavallaro, R., Cavallo, A. M., Cavallo, G., Cavion, M. T., Cavirani, G., Cazzaniga, F., Cazzetta, D., Cecconi, V., Cefalo, A., Celebrano, M., Celora, A., Centonze, P., Cerati, D., Cesaretti, D., Checchia, G., Checchin, A., Cherubini, M., Chianese, L., Chiappa, A., Chiappa, M. V., Chiariello, G., Chiavini, G., Chicco, M., Chiumeo, F., Ciacciarelli, A., Ciaci, D., Ciancaglini, R., Cicale, C., Cicale, S., Cipolla, A., Ciruolo, A., Citeri, A. L., Citterio, G., Clerici, M., Coazzoli, E., Collecchia, G., Colletta, F., Colombo, I., Colorio, P., Coluccia, S., Comerio, M., Comoretto, P., Compagni, M., Conte, O., Contri, S., Contrisciani, A., Coppetti, T., Corasaniti, F., Corradi, M. T., Corsano, A., Corsini, A., Corti, N., Costantini, G., Costantino, A., Cotroneo, S., Cozzi, D., Cravello, M. G., Cristiano, E., Cucchi, R., Cusmai, L., D'Errico, G. B., D'Agostino, P., Dal Bianco, L., Dal Mutto, U., Dal Pozzo, G., Dallapiccola, P., Dallatorre, G., Dalle Molle, G., Dalloni, E., D'Aloiso, A., D'Amicis, G., Danese, R., Danieli, D., Danisi, G., D'Anna, M. A., Danti, G., D'Ascanio, S., Davidde, G., De Angeli, D., De Bastiani, R., De Battisti, A., De Bellis, A., De Berardinis, G., De Carlo, F., De Giorgi, D., De Gobbi, R., De Lorenzis, E., De Luca, P., De Martini, G., De Marzi, M., De Matteis, D., De Padova, S., De Polo, P., De Sabato, N., De Stefano, T., De Vita, M. T., De Vito, U., De Zolt, V., Debernardi, F., Del Carlo, A., Del Re, G., Del Zotti, F., D'Elia, R., Della Giovanna, P., Dell'Acqua, L., Dell'Orco, R. L., Demaria, G., Di Benedetto, M. G., Di Chiara, G., Di Corcia, V., Di Domizio, O., Di Donato, P., Di Donato, S., Di Fermo, G., Di Franco, M., Di Giovannantonio, G., Di Lascio, G., Di Lecce, G., Di Lorenzo, N., Di Maro, T., Di Mattia, Q., Di Michele, E., Di Modica, R. S., Di Murro, D., Di Noi, M. C., Di Paoli, V., Di Santi, M., Di Sanzo, A., Di Turi, C., Diazzi, A., Dileo, I., D'Ingianna, A. P., Dolci, A., Dona, G., Donato, C., Donato, P., Donini, A., Donna, M. E., Donvito, T. V., Esposito, L., Esposito, N., Evangelista, M., Faita, G., Falco, M., Falcone, D. A., Falorni, F., Fanciullacci, A., Fanton, L., Fasolo, L., Fassina, R., Fassone, A., Fatarella, P., Fedele, F., Fera, I., Fera, L., Ferioli, S., Ferlini, M. G., Ferlino, R., Ferrante, G., Ferrara, F. N., Ferrarese, M. F., Ferrari, G., Ferrari, O., Ferreri, A., Ferroni, M., Fezzi, G., Figaroli, C., Fina, M. G., Fioretta, A., Fiorucci, C., Firrincieli, R., Fischetti, M., Fischietti, G., Fiume, D. C., Flecchia, G., Forastiere, G., Fossati, B., Franceschi, P. L., Franchi, L., Franzoso, F., Frapporti, G., Frasca, G., Frisotti, A., Fumagalli, G., Fusco, D., Gabriele, P., Gabrieli, A., Gagliano, D., Galimberti, G., Galli, A., Gallicchio, N., Gallio, F., Gallipoli, T., Gallo, P., Galopin, T., Gambarelli, L., Garbin, A., Garozzo, G. M., Gasparri, R., Gastaldo, M., Gatti, E., Gazzaniga, P., Gennachi, N., Gentile, R. V., Germani, P., Gesualdi, F., Gherardi, E., Ghezzi, C., Ghidini, M. G., Ghionda, F., Giacci, L., Gialdini, D., Giampaolo, C., Giancane, R., Giannanti, A., Giannese, S., Giannini, L., Giaretta, M., Giaretta, R., Giavardi, L., Giordano, P., Giordano, E., Giordano, B., Gioria, G. M., Giugliano, R., Grassi, E. A., Greco, A., Greco, L., Grilletti, N., Grimaldi, N., Grisetti, G., Groppelli, G., Gualtieri, L., Guarducci, M., Guastella, G., Guerra, M., Guerrini, F., Guglielmini, A., Guido, A., Gulotta, P., Iacono, E., Iadarola, G., Ianiro, G., Iarussi, V., Ieluzzi, M. L., Ierardi, C., Ingaldi, F., Interlandi, S., Iocca, M., Iorno, A., Ioverno, E., Iurato, R., La Pace, L., La Piscopia, C., La Selva, R., Lafratta, M., Lamparelli, M., Lanaro, G., Lancerotto, R., Larcher, M., Lassandro, M., Lattuada, G., Laurino, P., Lefons, C., Legrottaglie, F., Lemma, A., Leone, D., Leone, F., Leso, A., Leuzzi, G., Levato, G., Libardi, L., Libralesso, N., Licini, P. I., Licursi, G., Lidonnici, F., Lillo, C., Liveri, L., Livio, A., Loiero, R. A., Loison, M., Lombardo, G., Lombardo, T., Lomunno, V., Lomuscio, S., Lonedo, A., Longo, E., Lora, L., Lotterio, A., Lucatello, L., Luongo, A., Lupoli, M., Macchia, C., Macri, G., Mafessanti, M., Maggialetti, V., Maggioni, A., Magnani, M., Maiellaro, G., Mancuso, A., Maniglio, A. R., Mannari, G. L., Manni, A., Manocchio, B., Mao, M., Marano, A., Maraone, E., Marascio, D., Marcheselli, P., Marchetto, B., Marchetto, S., Marchi, A., Marchi, G. L., Mariano, C., Marinacci, S., Marinelli, S., Marini, G., Marra, V. C., Marrali, F., Marseglia, C., Martello, G., Martino, C., Martino, G., Martino, M., Marulli, C. F., Maruzzi, G., Marzotti, A., Mascheroni, G., Mascolo, P., Masoch, G., Masone, R., Massa, L., Massafra, M., Massi, M., Massignani, D. M., Matarese, A. M., Matini, G., Mauro, R., Mazzi, M., Mazzillo, A., Mazzocato, E., Mazzoleni, N. S., Mazzone, A., Melacci, A., Mele, E., Meliota, P., Menaspa, S., Meneghello, F., Merola, G., Merone, L., Metrucci, A., Mezzina, V., Micchi, A., Michielon, A., Migliore, N., Minero, G., Minotta, F., Mirandola, C., Mistrorigo, S., Modafferi, L., Moitre, R., Mola, E., Monachese, C., Mongiardini, C., Montagna, F., Montani, M., Montemurno, I., Montolli, R., Montorsi, S., Montresor, M., Monzani, M. G., Morabito, F., Mori, G., Moro, A., Mosca, M. F., Motti, F., Muddolon, L., Mugnai, M., Muscas, F., Naimoli, F., Nanci, G., Nargi, E., Nasorri, R., Nastrini, G., Negossi, M., Negrini, A., Negroni, A., Neola, V., Niccolini, F., Niro, C. M., Nosengo, C., Novella, G., Nuti, C., Obici, F., Olita, C., Oliverio, S. S., Olivieri, I., Oriente, S., Orlando, G., Paci, C., Pagano, G., Pagliara, C., Paita, G., Paladini, G., Paladino, G., Palano, T., Palatella, A., Palermo, P., Palmisano, M., Pando, P., Panessa, P., Panigo, F., Panozzo, G., Panvini, F., Panzieri, F., Panzino, A., Panzitta, F., Paoli, N., Papagna, R., Papaleo, M. G., Papalia, G., Parisi, R., Parotti, N., Parravicini, D., Passarella, P., Pastore, G. A., Patafio, M., Pavone, P., Pedroli, W., Pedroni, M., Pelligra, G., Pellizzari, M., Penati, A., Perlot, M., Perrone, A., Perrone, G., Peruzzi, P., Peselli, C., Petracchini, L., Petrera, L., Petrone, S., Peverelli, C., Pianorsi, F., Piazza, G. P., Piazzolla, G., Picci, A., Pienabarca, G., Pietronigro, T. P., Pignocchino, P., Pilone, R., Pinto, D., Pirovano, E., Pirrotta, D., Pisante, V., Pitotto, P., Pittari, L., Piva, A., Pizzoglio, A., Plantera, O. R., Plebani, W., Plessi, S., Podrecca, D., Poerio, V., Poggiani, F., Pogliani, W., Poli, L., Poloni, F. G., Porcelli, R., Porto, S., Pranzo, L., Prevedello, C., Profeta, C., Profico, D., Punzi, A., Quaglia, G. M., Racano, M., Raccone, A., Radice, F., Raho, C. A., Raimondi, R., Raino, M., Ramponi, R., Ramunni, A., Ramunni, A. L., Ravasio, F., Ravera, M., Re Sarto, G., Rebustello, G., Regazzoli, S., Restelli, C., Rezzonico, M., Ricchiuto, F., Rigo, S., Rigon, G., Rigon, R., Rinaldi, O. V., Rinaldi, M., Risplendente, P. G., Rispoli, M., Riundi, R., Riva, M. G., Rizzi, A. L., Rizzi, D., Rizzo, L. D., Rocchi, L., Rondinone, B., Rosa, B., Rosati, F., Roselli, F., Rossetti, A., Rossetti, C., Rossi, R., Rossi, P. R., Rossi, A., Rossi, C. L., Rossitto, A., Ruffini, R., Ruffo, A., Ruggio, S., Ruo, M., Russo, B., Russo, L., Russo, R., Russo, S., Russo, U., Russo, V., Ruta, G., Sacchi, F., Sacco Botto, F., Saia, A., Salladini, G., Salmoiraghi, S., Saluzzo, F., Salvatore, C., Salvatori, E., Salvio, G., Sandri, P., Sandrini, T., Sangermano, V., Santoni, N., Saracino, A. D., Saracino, A., Sarasin, P., Sardo Infirri, C., Sarri, B., Sartori, G., Sartori, N., Sauro, C., Scaglioni, M., Scalfi, C., Scamardella, A. M., Scandale, G., Scandone, L., Scannavini, G., Scarati, R., Scardi, A., Scarpa, F. M., Scazzi, P., Schifone, A., Schiroso, G., Scigliano, G., Scilla, A., Sciortino, M., Scolaro, G., Scollo, E., Scorretti, G., Sellitti, R., Selmo, A., Selvaggio, G., Sempio, A., Seren, F., Serio, L., Serra, C., Serra, L., Siciliano, D., Sideri, A., Sighele, M., Signore, R., Siliberto, F., Silvestro, M., Simioni, G., Simmini, G., Simonato, L., Sinchetto, F., Sizzano, E., Smajato, G., Smaldone, M., Sola, G., Sordillo, L., Sovran, C. S., Spagnul, P., Spano, F., Sproviero, S., Squintani, A., Stella, L., Stilo, V., Stocchiero, B., Stornello, M. C., Stracka, G., Strada, S., Stranieri, G., Stucci, N., Stufano, N., Suppa, A., Susca, V. G., Sutti, M., Taddei, M., Tagliabue, E., Tagliente, G., Talato, F., Talerico, P., Talia, R., Taranto, R., Tartaglia, M., Tauro, N., Tedesco, A., Tieri, P., Tirelli, M., Tocci, L., Todesco, P., Tognolo, M., Tomba, A., Tonello, P., Tonon, R., Toscano, L., Tosi, A., Tosi, G., Toso, S., Travaglio, P., Tremul, L., Tresso, C., Triacchini, P., Triggiano, L., Trigilio, A., Trimeloni, J., Tripicchio, G., Tritto, G. S., Trono, F., Trotta, E., Trotta, G., Tubertini, A., Turri, C., Turri, L., Tuttolani, M. P., Urago, M., Ursini, G., Valcanover, F., Valente, L., Valenti, M., Valentini, F., Vallone, G., Valz, P., Valzano, L., Vanin, V., Vatteroni, M., Vegetti, L., Vendrame, D., Veramonti, I., Veronelli, G., Vesco, A., Vicariotto, G., Vignale, G., Villa, P. L., Vinciguerra, R., Visco, A., Visentin, G., Visona, E., Vitali, E., Vitali, S., Vitti, F., Volpone, D. A., Zambon, N., Zammarrelli, A., Zanaboni, A., Zane, D., Zanetti, B., Zanibellato, R., Zappetti, M., Zappone, P., Zerilli, G., Zirino, V., Zoccali, R., Zuin, F., Altomonte, M., Anelli, N., Angio, F., Annale, P., Antonacci, S., Anzilotta, R., Bano, F., Basadonna, O., Beduschi, L., Becagli, P., Bellotti, G., Blotta, C., Bruno, G., Cappuccini, A., Caramatti, S., Cariolato, M. P., Castellana, M., Castellani, L., Catania, R., Chielli, A., Chinellato, A., Ciaccia, A., Clerici, E., Cocci, A., Costanzo, G., D'Ercole, F., De Stefano, G., Dece, F., Di Cicco, N., Di Marco, A., Donati Sarti, C., Draghi, E., Dusi, G., Esposito, V., Ferraro, L., Ferretti, A., Ferri, E., Foggetti, L., Foglia, A., Fonzi, E., Frau, G., Fuoco, M. R., Furci, G., Gallo, L., Garra, V., Giannini, A., Gris, A., Iacovino, R., Interrigi, R., Joppi, R., Laner, B., La Fortezza, G., La Padula, A., Lista, M. R., Lupi, G., Maffei, D., Maggioni, G., Magnani, L., Marrazzo, E., Marcon, L., Marino, V., Maroni, A., Martinelli, C., Mastandrea, E., Mastropierro, F., Meo, A. T., Mero, P., Minesso, E., Moschetta, V., Mosele, E., Nanni, C., Negretti, A., Nistico, C., Orsini, A., Osti, M., Pacilli, M. C., Pennestre, C., Picerno, G., Piol, K., Pivano, L., Pizzuti, E., Poggi, L., Poidomani, I., Pozzetto, M., Presti, M. L., Ravani, R., Recalenda, V., Romagnuolo, F., Rossignoli, S., Rossin, E., Sabatella, C., Sacco, F., Sanita, F., Sansone, E., Servadei, F., Sisto, M. T., Sorio, A., Sorrentino, A., Spinelli, E., Spolaor, A., Squillacioti, A., Stella, P., Talerico, A., Todisco, C., Vadino, M., and Zuliani, C.
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Overweight ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Prediction model ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Diabetes Mellitus ,Medicine ,Humans ,Multicenter Studies as Topic ,Myocardial infarction ,Risk factor ,education ,Stroke ,Aged ,Randomized Controlled Trials as Topic ,education.field_of_study ,Lifestyle habits ,business.industry ,Major cardiovascular events ,Atrial fibrillation ,General Medicine ,Middle Aged ,medicine.disease ,Cardiovascular Diseases ,Heart failure ,Physical therapy ,Female ,medicine.symptom ,business ,Diabetic Angiopathies - Abstract
To verify whether it is possible, in people with diabetes mellitus (DM) considered at very high cardiovascular (CV) risk, stratify this risk better and identify significant modifiable risk factor (including lifestyle habits) to help patients and clinicians improve CV prevention. People with DM and microvascular diseases or one or more CV risk factors (hypertension, hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity) included in the Risk and Prevention study were selected. We considered the combined endpoint of non-fatal acute myocardial infarction and stroke and CV death. A multivariate Cox proportional analysis was carried out to identify relevant predictors. We also used the RECPAM method to identify subgroups of patients at higher risk. In our study, the rate of major CV events was lower than expected (5 % in 5 years). Predictors of CV events were age, male, sex, heart failure, previous atherosclerotic disease, atrial fibrillation, insulin treatment, high HbA1c, heart rate and other CV diseases while being physically active was protective. RECPAM analysis indicated that history of atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI 3.04–6.69). Among subjects with no previous atherosclerotic disease, men with HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86–4.14) with respect to women. In this population, the rate of major CV events was lower than expected. This prediction model could help clinicians identify people with DM at higher CV risk and support them in achieving goals of physical activity and HbA1c.
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- 2016
3. Final Height of Patients with Turner’s Syndrome Treated with Growth Hormone (GH): Indications for GH Therapy Alone at High Doses and Late Estrogen Therapy
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Cacciari E., Mazzanti L., Bergamaschi R., Perri A., Scarano E., Chiumello G., Guarnieri M. P., Rigon F., Licersi A., Pasquino A. M., Pucarelli I., Di Maio S., Severi F., Larizza D., Bernasconi S., Buzi F., Matarazzo P., Cavallo L., Saggese G., Tonini G., Sposito M., Gabrielli O., Radetti G., De Luca F., Borrelli P., Morabito F., Bona G., SALERNO, MARIACAROLINA, Cacciari, E., Mazzanti, L., Bergamaschi, R., Perri, A., Scarano, E., Chiumello, G., Guarnieri, M. P., Rigon, F., Licersi, A., Pasquino, A. M., Pucarelli, I., Di Maio, S., Salerno, Mariacarolina, Severi, F., Larizza, D., Bernasconi, S., Buzi, F., Matarazzo, P., Cavallo, L., Saggese, G., Tonini, G., Sposito, M., Gabrielli, O., Radetti, G., De Luca, F., Borrelli, P., Morabito, F., and Bona, G.
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medicine.medical_specialty ,Chemotherapy ,Gonad ,medicine.drug_class ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Final height, Turner's syndrome, growth hormone, GH therapy, estrogen therapy, Italian Study Group for Turner Syndrome ,Biochemistry (medical) ,Clinical Biochemistry ,Oxandrolone ,medicine.disease ,Biochemistry ,Group A ,Endocrinology ,medicine.anatomical_structure ,El Niño ,Estrogen ,Internal medicine ,Turner syndrome ,medicine ,Menarche ,business ,medicine.drug - Abstract
We report final height data of patients with Turner's syndrome collected by the Italian Study Group for Turner's Syndrome. One hundred and thirty-five patients reached their final height during GH therapy with different therapeutic regimens (dose and combination). They were divided into 3 groups: group A, 74 patients with high doses of GH (1 IU/kg/week) for at least 2 yr; group A1, GH alone and estrogen therapy added not before 14 yr of chronological age (47 patients, of whom 30 were treated for >4 yr and 10 for >6 yr); group A2, GH plus ethinyl estradiol (17 patients) or GH plus oxandrolone (10 patients); group B, 51 patients with low doses of GH (0.5 IU/kg-week) and high doses of GH for less than 2 yr; and group C, 10 patients with high doses of GH with spontaneous menarche. In contrast to the patients of groups B and C, the patients of group A showed a significantly higher final height (mean, 147.5+/-6.5 cm) than their projected height (mean, 142.9+/-6.4 cm). They showed also a significantly higher final height compared to the subjects of groups B (mean, 145.6+/-5.7 cm) and C (mean, 143.0+/-5.3). Among the patients of group A, the best results were obtained in the patients of group A1 treated with GH alone at high doses and for a longer period (4 yr, 149.3+/-6.4 cm; 6 yr, 153.8+/-4.0 cm). Karyotype, GH secretion, and birth weight did not influence the efficacy of GH therapy. A low target height and a high prevalence of a spontaneous ovarian activity or menarche may negatively influence the effect of GH therapy. Estrogens did not improve final height when added to GH therapy. The use of small doses of oxandrolone was not effective in our experience. GH therapy provides a satisfactory auxological result, especially with high doses of GH alone, given for a long period of time. Optimization of the treatment would seem to require the identification of the ideal age for starting therapy, and this is only possible with a specially designed multicenter study.
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- 1999
4. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma
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Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio COLLABORATORI: Tosi, P, Motta, Mr, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, Franco, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, Mc, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, Am, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, Mc, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E., Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A., Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio, Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, and Quartarone, E
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Male ,Boronic Acid ,medicine.medical_treatment ,PLUS DEXAMETHASONE ,Phases of clinical research ,Kaplan-Meier Estimate ,Hematopoietic stem cell transplantation ,Biochemistry ,Antineoplastic Agent ,Bortezomib-thalidomide-dexamethasone ,Bortezomib ,Immunosuppressive Agent ,Autologous stem-cell transplantation ,MULTIPLE MYELOMA ,Antineoplastic Combined Chemotherapy Protocols ,thalidomide-dexamethasone ,Multiple myeloma ,RANDOMIZED PHASE-3 ,LENALIDOMIDE ,STEM CELL TRANSPLANTATION ,Hematopoietic Stem Cell Transplantation ,PHASE-III TRIAL ,Hematology ,Middle Aged ,CHEMOTHERAPY ,Prognosis ,Boronic Acids ,Combined Modality Therapy ,Thalidomide ,Transplantation, Autologou ,Pyrazines ,HIGH-DOSE MELPHALAN ,INDUCTION TREATMENT ,Female ,Autologous ,Immunosuppressive Agents ,Pyrazine ,Human ,medicine.drug ,MAINTENANCE THERAPY ,medicine.medical_specialty ,DOXORUBICIN ,Antineoplastic Agents, Hormonal ,Prognosi ,Immunology ,Urology ,Antineoplastic Agents ,dexamethasone ,Transplantation, Autologous ,Disease-Free Survival ,Dexamethasone ,Humans ,Multiple Myeloma ,Cell Biology ,medicine ,Autologous transplantation ,METAANALYSIS ,Transplantation ,Antineoplastic Combined Chemotherapy Protocol ,Hormonal ,business.industry ,medicine.disease ,Surgery ,business ,Settore MED/15 - Malattie del Sangue - Abstract
In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.
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- 2012
5. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment
- Author
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Morabito, F, Gentile, M, Mazzone, C, Rossi, D, Di Raimondo, F, Bringhen, S, Ria, R, Offidani, M, Patriarca, F, Nozzoli, C, Petrucci, Mt, Benevolo, G, Vincelli, I, Guglielmelli, T, Grasso, M, Marasca, R, Baldini, L, Montefusco, V, Musto, P, Cascavilla, N, Majolino, I, Musolino, Caterina, Cavo, M, Boccadoro, M, Palumbo, A, Musolino, C., Morabito F., Gentile M., Mazzone C., Rossi D., Di Raimondo F., Bringhen S., Ria R., Offidani M., Patriarca F., Nozzoli C., Petrucci M.T., Benevolo G., Vincelli I., Guglielmelli T., Grasso M., Marasca R., Baldini L., Montefusco V., Musto P., Cascavilla N., Majolino I., Musolino C., Cavo M., Boccadoro M., and Palumbo A.
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Melphalan ,Male ,CHRONIC KIDNEY-DISEASE ,DOXORUBICIN-DEXAMETHASONE BDD ,PRESENTING FEATURES ,FAILURE ARF ,PHASE-II ,REGIMENS ,REVERSIBILITY ,PATHOGENESIS ,REVERSAL ,SURVIVAL ,Biochemistry ,Bortezomib ,chemistry.chemical_compound ,MULTIPLE MYELOMA ,Prednisone ,Multiple myeloma ,Antineoplastic Combined Chemotherapy Protocols ,Multiple Myeloma ,thalidomide ,bortezomib-melphalan-prednisone ,Kidney ,treatment ,Hematology ,Induction Chemotherapy ,Boronic Acids ,Neoadjuvant Therapy ,Thalidomide ,medicine.anatomical_structure ,Treatment Outcome ,Pyrazines ,Female ,Kidney Diseases ,medicine.drug ,Glomerular Filtration Rate ,renal impairment ,medicine.medical_specialty ,Immunology ,Urology ,Renal function ,MPT-VT ,Maintenance Chemotherapy ,medicine ,Humans ,Adverse effect ,Aged ,Creatinine ,business.industry ,Cell Biology ,medicine.disease ,Survival Analysis ,Surgery ,melphalan ,chemistry ,VMP ,prednisone ,bortezomib-melphalan-prednisone-thalidomide ,business - Abstract
We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan-prednisone (VMP). Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min), moderate RI (eGFR 31-50 mL/min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P = .022) and moderate RI (P = .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP. This study is registered at http://www.clinicaltrials.gov as NCT01063179.
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- 2011
6. Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study
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Gallamini, A., Stelitano, C., Calvi, R., Bellei, M., Mattei, D., Vitolo, U., Morabito, F., Martelli, M., Brusamolino, E., Iannitto, E., Zaja, F., Cortellazzo, S., Rigacci, L., Devizzi, L., Todeschini, G., Santini, G., Brugiatelli, M., Federico, M., Intergruppo Italiano Linfomi, Liberati, Anna Marina, Gallamini, A, Stelitano, C, Calvi, R, Bellei, M, Mattei, D, Vitolo, U, Morabito, F, Martelli, M, Brusamolino, E, Iannitto, E, Zaja, Francesco, Cortelazzo, S, Rigacci, L, Devizzi, L, Todeschini, G, Santini, G, Brugiatelli, M, and Federico, M.
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Male ,medicine.medical_specialty ,Multivariate analysis ,Time Factors ,B-CELL ,Immunology ,Peripheral T-cell lymphoma not otherwise specified ,Antineoplastic Agents ,Lymphoma, T-Cell ,Biochemistry ,Gastroenterology ,NHL ,REAL CLASSIFICATION ,Peripheral T-cell lymphoma ,new prognostic model ,PROPOSAL ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,NON-HODGKINS-LYMPHOMA ,Stage (cooking) ,Neoplasm Staging ,Retrospective Studies ,RISK ,Univariate analysis ,Performance status ,business.industry ,Patient Selection ,Cell Biology ,Hematology ,CHEMOTHERAPY ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Survival Analysis ,Surgery ,Lymphoma ,Relative risk ,Female ,business ,Follow-Up Studies ,Stem Cell Transplantation - Abstract
To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years ( P = .0002), equal to or more than 2 extranodal sites ( P = .0002), lactic dehydrogenase (LDH) value at normal levels or above ( P < .0001), performance status (PS) equal to or more than 2 ( P ≤ .0001), stage III or higher ( P = .0001), and bone marrow involvement ( P = .0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309; P < .0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327, P < .0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P < .0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P = .026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4, 3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively ( P ≤ .0001; log-rank, 66.79).
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- 2004
7. N-3 fatty acids in patients with multiple cardiovascular risk factors
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Roncaglioni, Maria Carla, Avanzini, Fausto, Barlera, Simona, Marzona, Irene, Milani, Valentina, Tombesi, Massimo, Caimi, Vittorio, Longoni, Paolo, Silletta, Maria Giuseppina, Tognoni, Gianni, Marchioli, Avanzini F, Roberto., Caimi, V, Longoni, P, Marchioli, R, Roncaglioni, Mc, Silletta, Mg, Tognoni, G, Tombesi, M, Barlera, S, Milani, V, Nicolis, Eb, Casola, C, Marzona, I, Massa, E, Marrocco, W, Micalella, M, Avanzini, F, Franzosi, Mg, Geraci, E, Giansiracusa, N, Rocchetti, L, Decarli, A, Satolli, R, Alli, C, Beghi, E, Bertele', V, Volpi, A, Baviera, M, Monesi, L, Pangrazzi, I, Nicolis, E, Clerici, F, Palumbo, A, Sgaroni, G, Pioggiarella, R, Scarano, M, Marfisi, Rm, Flamminio, A, Macino, L, Ferri, B, Pera, C, Polidoro, A, Abbatino, D, Acquati, M, Addorisio, G, Adinolfi, D, Adreani, L, Agistri, Mr, Agneta, A, Agnolio, Ml, Agostini, N, Agostino, G, Airò, A, Alaimo, N, Albano, M, Albano, N, Alecci, G, Alemanno, S, Alexanian, A, Alfarano, M, Alfè, L, Alonzo, N, Alvino, S, Ancora, A, Andiloro, S, Andreatta, E, Angeli, S, Angiari, F, Angilletti, V, Annicchiarico, C, Anzivino, M, Aprea, R, Aprile, A, Aprile, E, Aprile, I, Aprile, L, Armellani, V, Arnetoli, M, Aronica, A, Autiero, V, Bacca, G, Baccalaro, Am, Bacci, M, Baglio, G, Bagnani, M, Baiano, A, Baldari, A, Ballarini, L, Banchi, G, Bandera, R, Bandini, F, Baratella, M, Barbieri, A, Barbieri Vita, A, Bardi, M, Barlocchi, M, Baron, P, Bartoli, M, Basile, A, Basile, F, Basile, S, Battaggia, A, Battaglia, A, Baù, A, Beconcini, G, Beggio, R, Belfiore, Pa, Belicchi, M, Bellamoli, S, Bellini, C, Bellomo, M, Benetollo, C, Benetti, R, Beretta, E, Bertalero, P, Bertaso, Fg, Bertolani, U, Bettelli, G, Biagiotti, G, Bianchi, S, Bianco, G, Biccari, F, Bigioli, F, Bindi, M, Bisanti, G, Bitetti, Em, Blasetti, Mp, Blesi, F, Boato, V, Boga, S, Boidi, E, Boldrin, G, Bollati, A, Bolzan, L, Bolzonella, S, Bonardi, P, Bonato, Gb, Bonci, M, Bonfitto, G, Bonincontro, E, Boninsegna, F, Bonissone, D, Bono, L, Bonollo, E, Borghi, M, Borioli, N, Borsatto, M, Bosco, T, Bosisio Pioltelli, M, Botarelli, C, Botassis, S, Bottini, F, Bottos, C, Bova, G, Bova, V, Bozzani, A, Bozzetto, Rm, Braga, Vt, Braglia, M, Bramati, E, Brazzoli, C, Breglia, G, Brescia, A, Briganti, D, Brigato, G, Brocchi, A, Brosio, Fa, Bruni, E, Buscaglia, E, Bussini, Md, Bussotti, A, Buzzaccarini, F, Buzzatti, A, Caccamo, G, Cacciavillani, C, Caggiano, G, Calciano, Fp, Calderisi, M, Calienno, S, Caltagirone, P, Calzolari, I, Cammisa, M, Campanaro, M, Campanella, Gb, Campese, F, Canali, G, Candiani, De, Canepa, R, Canini, D, Canino, A, Cantoro, Ea, Capilupi, V, Capotosto, P, Cappelli, B, Capraro, G, Carafa, Fa, Carano, Q, Carcaterra, V, Carriero, D, Carrozzo, G, Cartanese, M, Casalena, M, Casarola, M, Caso, C, Casotto, M, Castaldi, F, Castegnaro, R, Castellani, G, Castri, S, Catalano, E, Catinello, N, Caturano, G, Cavallaro, R, Cavallo, Am, Cavallo, G, Cavion, Mt, Cavirani, G, Cazzaniga, F, Cazzetta, D, Cecconi, V, Cefalo, A, Celebrano, M, Celora, A, Centonze, P, Cerati, D, Cesaretti, D, Checchia, G, Checchin, A, Cherubini, M, Chianese, L, Chiappa, A, Chiappa, Mv, Chiariello, G, Chiavini, G, Chicco, M, Chiumeo, F, Ciacciarelli, A, Ciaci, D, Ciancaglini, R, Cicale, C, Cicale, S, Cipolla, A, Ciruolo, A, Citeri, Al, Citterio, G, Clerici, M, Coazzoli, E, Collecchia, G, Colletta, F, Colombo, I, Colorio, P, Coluccia, S, Comerio, M, Comoretto, P, Compagni, M, Conte, O, Contri, S, Contrisciani, A, Coppetti, T, Corasaniti, F, Corradi, Mt, Corsano, A, Corsini, A, Corti, N, Costantini, G, Costantino, A, Cotroneo, S, Cozzi, D, Cravello, Mg, Cristiano, E, Cucchi, R, Cusmai, L, D' Errico GB, D'Agostino, P, Dal Bianco, L, Dal Mutto, U, Dal Pozzo, G, Dallapiccola, P, Dallatorre, G, Dalle Molle, G, Dalloni, E, D'Aloiso, A, D'Amicis, G, Danese, R, Danieli, D, Danisi, G, D'Anna, Ma, Danti, G, D'Ascanio, S, Davidde, G, De Angeli, D, De Bastiani, R, De Battisti, A, De Bellis, A, De Berardinis, G, De Carlo, F, De Giorgi, D, De Gobbi, R, De Lorenzis, E, De Luca, P, De Martini, G, De Marzi, M, De Matteis, D, De Padova, S, De Polo, P, De Sabato, N, De Stefano, T, De Vita MT, De Vita, U, De Zolt, V, Debernardi, F, Del Carlo, A, Del Re, G, Del Zotti, F, D'Elia, R, Della Giovanna, P, Dell'Acqua, L, Dell'Orco, Rl, Demaria, G, Di Benedetto MG, Di Chiara, G, Di Corcia, V, Di Domizio, O, Di Donato, P, Di Donato, S, Di Fermo, G, Di Franco, M, Di Giovannantonio, G, Di Lascio, G, Di Lecce, G, Di Lorenzo, N, Di Maro, T, Di Mattia, Q, Di Michele, E, Di Modica RS, Di Murro, D, Di Noi MC, Di Paoli, V, Di Santi, M, Di Sanzo, A, Di Turi, C, Diazzi, A, Dileo, I, D'Ingianna, Ap, Dolci, A, Donà, G, Donato, C, Donato, P, Donini, A, Donna, Me, Donvito, Tv, Esposito, L, Esposito, N, Evangelista, M, Faita, G, Falco, M, Falcone, Da, Falorni, F, Fanciullacci, A, Fanton, L, Fasolo, L, Fassina, R, Fassone, A, Fatarella, P, Fedele, F, Fera, I, Fera, L, Ferioli, S, Ferlini, Mg, Ferlino, R, Ferrante, G, Ferrara, Fn, Ferrarese, Mf, Ferrari, G, Ferrari, O, Ferreri, A, Ferroni, M, Fezzi, G, Figaroli, C, Fina, Mg, Fioretta, A, Fiorucci, C, Firrincieli, R, Fischetti, M, Fischietti, G, Fiume, Dc, Flecchia, G, Forastiere, G, Fossati, B, Franceschi, Pl, Franchi, L, Franzoso, F, Frapporti, G, Frasca, G, Frisotti, A, Fumagalli, G, Fusco, D, Gabriele, P, Gabrieli, A, Gagliano, D, Galimberti, G, Galli, A, Gallicchio, N, Gallio, F, Gallipoli, T, Gallo, P, Galopin, T, Gambarelli, L, Garbin, A, Garozzo, Gm, Gasparri, R, Gastaldo, M, Gatti, E, Gazzaniga, P, Gennachi, N, Gentile, Rv, Germani, P, Gesualdi, F, Gherardi, E, Ghezzi, C, Ghidini, Mg, Ghionda, F, Giacci, L, Gialdini, D, Giampaolo, C, Giancane, R, Giannanti, A, Giannese, S, Giannini, L, Giaretta, M, Giaretta, R, Giavardi, L, Giordano, P, Giordano, E, Giordano, B, Gioria, Gm, Giugliano, R, Grassi, Ea, Greco, A, Greco, L, Grilletti, N, Grimaldi, N, Grisetti, G, Groppelli, G, Gualtieri, L, Guarducci, M, Guastella, G, Guerra, M, Guerrini, F, Guglielmini, A, Guido, A, Gulotta, P, Iacono, E, Iadarola, G, Ianiro, G, Iarussi, V, Ieluzzi, Ml, Ierardi, C, Ingaldi, F, Interlandi, S, Iocca, M, Iorno, A, Ioverno, E, Iurato, R, La Pace, L, La Piscopia, C, La Selva, R, Lafratta, M, Lamparelli, M, Lanaro, G, Lancerotto, R, Larcher, M, Lassandro, M, Lattuada, G, Laurino, P, Lefons, C, Legrottaglie, F, Lemma, A, Leone, D, Leone, F, Leso, A, Leuzzi, G, Levato, G, Libardi, L, Libralesso, N, Licini, Pi, Licursi, G, Lidonnici, F, Lillo, C, Liveri, L, Livio, A, Loiero, Ra, Loison, M, Lombardo, G, Lombardo, T, Lomunno, V, Lomuscio, S, Lonedo, A, Longo, E, Lora, L, Lotterio, A, Lucatello, L, Luongo, A, Lupoli, M, Macchia, C, Macri, G, Mafessanti, M, Maggialetti, V, Maggioni, A, Magnani, M, Maiellaro, G, Mancuso, A, Maniglio, Ar, Mannari, Gl, Manni, A, Manocchio, B, Mao, M, Maranò, A, Maraone, E, Marascio, D, Marcheselli, P, Marchetto, B, Marchetto, S, Marchi, A, Marchi, Gl, Mariano, C, Marinacci, S, Marinelli, S, Marini, G, Marra, Vc, Marrali, F, Marseglia, C, Martello, G, Martino, C, Martino, G, Martino, M, Marulli, Cf, Maruzzi, G, Marzotti, A, Mascheroni, G, Mascolo, P, Masoch, G, Masone, R, Massa, L, Massafra, M, Massi, M, Massignani, Dm, Matarese, Am, Matini, G, Mauro, R, Mazzi, M, Mazzillo, A, Mazzocato, E, Mazzoleni, Ns, Mazzone, A, Melacci, A, Mele, E, Meliota, P, Menaspà, S, Meneghello, F, Merola, G, Merone, L, Metrucci, A, Mezzina, V, Micchi, A, Michielon, A, Migliore, N, Minero, G, Minotta, F, Mirandola, C, Mistrorigo, S, Modafferi, L, Moitre, R, Mola, E, Monachese, C, Mongiardini, C, Montagna, F, Montani, M, Montemurno, I, Montolli, R, Montorsi, S, Montresor, M, Monzani, Mg, Morabito, F, Mori, G, Moro, A, Mosca, Mf, Motti, F, Muddolon, L, Mugnai, M, Muscas, F, Naimoli, F, Nanci, G, Nargi, E, Nasorri, R, Nastrini, G, Negossi, M, Negrini, A, Negroni, A, Neola, V, Niccolini, F, Niro, Cm, Nosengo, C, Novella, G, Nuti, C, Obici, F, Olita, C, Oliverio, Ss, Olivieri, I, Oriente, S, Orlando, G, Paci, C, Pagano, G, Pagliara, C, Paita, G, Paladini, G, Paladino, G, Palano, T, Palatella, A, Palermo, P, Palmisano, M, Pando, P, Panessa, P, Panigo, F, Panozzo, G, Panvini, F, Panzieri, F, Panzino, A, Panzitta, F, Paoli, N, Papagna, R, Papaleo, Mg, Papalia, G, Parisi, R, Parotti, N, Parravicini, D, Passarella, P, Pastore, Ga, Patafio, M, Pavone, P, Pedroli, W, Pedroni, M, Pelligra, G, Pellizzari, M, Penati, A, Perlot, M, Perrone, A, Perrone, G, Peruzzi, P, Peselli, C, Petracchini, L, Petrera, L, Petrone, S, Peverelli, C, Pianorsi, F, Piazza, Gp, Piazzolla, G, Picci, A, Pienabarca, G, Pietronigro, Tp, Pignocchino, P, Pilone, R, Pinto, D, Pirovano, E, Pirrotta, D, Pisante, V, Pitotto, P, Pittari, L, Piva, A, Pizzoglio, A, Plantera, Or, Plebani, W, Plessi, S, Podrecca, D, Poerio, V, Poggiani, F, Pogliani, W, Poli, L, Poloni, Fg, Porcelli, R, Porto, S, Pranzo, L, Prevedello, C, Profeta, C, Profico, D, Punzi, A, Quaglia, Gm, Racano, M, Raccone, A, Radice, F, Raho, Ca, Raimondi, R, Rainò, M, Ramponi, R, Ramunni, A, Ramunni, Al, Ravasio, F, Ravera, M, Re Sartò, G, Rebustello, G, Regazzoli, S, Restelli, C, Rezzonico, M, Ricchiuto, F, Rigo, S, Rigon, G, Rigon, R, Rinaldi, Ov, Rinaldi, M, Risplendente, Pg, Rispoli, M, Riundi, R, Riva, Mg, Rizzi, Al, Rizzi, D, Rizzo, Ld, Rocchi, L, Rondinone, B, Rosa, B, Rosati, F, Roselli, F, Rossetti, A, Rossetti, C, Rossi, R, Rossi, Pr, Rossi, A, Rossi, Cl, Rossitto, A, Ruffini, R, Ruffo, A, Ruggio, S, Ruo, M, Russo, B, Russo, L, Russo, R, Russo, S, Russo, U, Russo, V, Ruta, G, Sacchi, F, Sacco Botto, F, Saia, A, Salladini, G, Salmoiraghi, S, Saluzzo, F, Salvatore, C, Salvatori, E, Salvio, G, Sandri, P, Sandrini, T, Sangermano, V, Santoni, N, Saracino, Ad, Saracino, A, Sarasin, P, Sardo Infirri, C, Sarrì, B, Sartori, G, Sartori, N, Sauro, C, Scaglioni, M, Scalfi, C, Scamardella, Am, Scandale, G, Scandone, L, Scannavini, G, Scarati, R, Scardi, A, Scarpa, Fm, Scazzi, P, Schifone, A, Schirosa, G, Scigliano, G, Scilla, A, Sciortino, M, Scolaro, G, Scollo, E, Scorretti, G, Sellitti, R, Selmo, A, Selvaggio, G, Sempio, A, Seren, F, Serio, L, Serra, C, Serra, L, Siciliano, D, Sideri, A, Sighele, M, Signore, R, Siliberto, F, Silvestro, M, Simioni, G, Simmini, G, Simonato, L, Sinchetto, F, Sizzano, E, Smajato, G, Smaldone, M, Sola, G, Sordillo, L, Sovran, Cs, Spagnul, P, Spanò, F, Sproviero, S, Squintani, A, Stella, L, Stilo, V, Stocchiero, B, Stornello, Mc, Stracka, G, Strada, S, Stranieri, G, Stucci, N, Stufano, N, Suppa, A, Susca, Vg, Sutti, M, Taddei, M, Tagliabue, E, Tagliente, G, Talato, F, Talerico, P, Talia, R, Taranto, R, Tartaglia, M, Tauro, N, Tedesco, A, Tieri, P, Tirelli, M, Tocci, L, Todesco, P, Tognolo, M, Tomba, A, Tonello, P, Tonon, R, Toscano, L, Tosi, A, Tosi, G, Toso, S, Travaglio, P, Tremul, L, Tresso, C, Triacchini, P, Triggiano, L, Trigilio, A, Trimeloni, J, Tripicchio, G, Tritto, Gs, Trono, F, Trotta, E, Trotta, G, Tubertini, A, Turri, C, Turri, L, Tuttolani, Mp, Urago, M, Ursini, G, Valcanover, F, Valente, L, Valenti, M, Valentini, F, Vallone, G, Valz, P, Valzano, L, Vanin, V, Vatteroni, M, Vegetti, L, Vendrame, D, Veramonti, I, Veronelli, G, Vesco, A, Vicariotto, G, Vignale, G, Villa, Pl, Vinciguerra, R, Visco, A, Visentin, G, Visonà, E, Vitali, E, Vitali, S, Vitti, F, Volpone, Da, Zambon, N, Zammarrelli, A, Zanaboni, A, Zane, D, Zanetti, B, Zanibellato, R, Zappetti, M, Zappone, P, Zerilli, G, Zirino, V, Zoccali, R, Zuin, F, Altomonte, M, Anelli, N, Angiò, F, Annale, P, Antonacci, S, Anzilotta, R, Bano, F, Basadonna, O, Beduschi, L, Becagli, P, Bellotti, G, Blotta, C, Bruno, G, Cappuccini, A, Caramatti, S, Cariolato, Mp, Castellana, M, Castellani, L, Catania, R, Chielli, A, Chinellato, A, Ciaccia, A, Clerici, E, Cocci, A, Costanzo, G, D'Ercole, F, De Stefano, G, Decè, F, Di Cicco, N, Di Marco, A, Donati Sarti, C, Draghi, E, Dusi, G, Esposito, V, Ferraro, L, Ferretti, A, Ferri, E, Foggetti, L, Foglia, A, Fonzi, E, Frau, G, Fuoco, Mr, Furci, G, Gallo, L, Garra, V, Giannini, A, Gris, A, Iacovino, R, Interrigi, R, Joppi, R, Laner, B, La Fortezza, G, La Padula, A, Lista, Mr, Lupi, G, Maffei, D, Maggioni, G, Magnani, L, Marrazzo, E, Marcon, L, Marinò, V, Maroni, A, Martinelli, C, Mastandrea, E, Mastropierro, F, Meo, At, Mero, P, Minesso, E, Moschetta, V, Mosele, E, Nanni, C, Negretti, A, Nisticò, C, Orsini, A, Osti, M, Pacilli, Mc, Pennestre, C, Picerno, G, Piol, K, Pivano, L, Pizzuti, E, Poggi, L, Poidomani, I, Pozzetto, M, Presti, Ml, Ravani, R, Recalenda, V, Romagnuolo, F, Rossignoli, S, Rossin, E, Sabatella, C, Sacco, F, Sanità, F, Sansone, E, Servadei, F, Sisto, Mt, Sorio, A, Sorrentino, A, Spinelli, E, Spolaor, A, Squillacioti, A, Stella, P, Talerico, A, Todisco, C, Vadino, M, and Zuliani, C.
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Male ,medicine.medical_specialty ,General Practice ,Kaplan-Meier Estimate ,Placebo ,Double-Blind Method ,Risk Factors ,Internal medicine ,Fatty Acids, Omega-3 ,Clinical endpoint ,medicine ,Humans ,Myocardial infarction ,Treatment Failure ,Aged ,Proportional Hazards Models ,chemistry.chemical_classification ,Omega-3 ,business.industry ,Proportional hazards model ,Medicine (all) ,Hazard ratio ,Fatty Acids ,General Medicine ,Middle Aged ,medicine.disease ,Hospitalization ,Primary Prevention ,chemistry ,Cardiovascular Diseases ,Heart failure ,Cohort ,Female ,business ,Polyunsaturated fatty acid - Abstract
Background Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction. Methods In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes. Results Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points. Conclusions In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Societa Prodotti Antibiotici and others; ClinicalTrials.gov number, NCT00317707.).
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- 2013
8. Clinical categories identified by a new prognostic index reflect biological characteristics of patients in early chronic lymphocytic leukemia: The Gruppo Italiano Studio Linfomi (GISL) experience
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Molica, S, DI RAIMONDO, F, Cutrona, G, Fabris, S, Mauro, Francesca Romana, Brugiatelli, M, Baldini, L, Musto, P, Sacchi, S, Cortelezzi, A, Foa, Roberto, Neri, A, Federico, M, Ferrarini, M, Morabito, F, and GRUPPO ITALIANO STUDIO LINFOMI GISL
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Oncology ,Cancer Research ,medicine.medical_specialty ,Index (economics) ,Clinical score ,Chronic lymphocytic leukemia ,Internal medicine ,medicine ,Biological validation ,Humans ,Multicenter Studies as Topic ,CLL, Clinical score, Biological validation ,business.industry ,clinical score ,Hematology ,medicine.disease ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,CLL ,biological validation ,Physical therapy ,business ,Studio - Published
- 2010
9. Quantitative molecular evaluation in autotransplant programs for follicular lymphoma: efficacy of in vivo purging by Rituximab
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Galimberti, S, Guerrini, F, Morabito, F, Palumbo, Ga, DI RAIMONDO, Francesco, Papineschi, F, Caracciolo, F, Fazzi, R, Cervetti, G, Cuzzocrea, A, Petrini, M., and Palumbo, Giuseppe Alberto Maria
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Follicular lymphoma ,CHOP ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Transplantation, Autologous ,Disease-Free Survival ,Antibodies, Monoclonal, Murine-Derived ,In vivo ,Internal medicine ,medicine ,Autologous transplantation ,Humans ,Leukapheresis ,Lymphoma, Follicular ,Gene Rearrangement ,Transplantation ,Peripheral Blood Stem Cell Transplantation ,business.industry ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,medicine.disease ,Neoplastic Cells, Circulating ,Minimal residual disease ,Genes, bcl-2 ,Graft-versus-host disease ,Molecular Diagnostic Techniques ,Immunology ,Rituximab ,Female ,business ,medicine.drug - Abstract
The main aim of this paper was to compare results of Genescan and real-time PCR methods in order to detect contamination in harvests from patients with follicular lymphoma. The secondary goal was to evaluate the efficacy of Rituximab as an in vivo purging agent. A total of 23 patients had been treated with CHOP followed by either high-dose therapy (12 patients) or high-dose plus Rituximab (11 patients), both followed by autologous transplantation. Results show that 86% of harvests from patients treated whith Rituximab were PCR-negative compared to 14.3% from controls. Real-time PCR was more sensitive than Genescan PCR; quantitative analysis revealed a correlation between the amount of contamination in the harvests and relapse after transplantation. Whereas all patients reinfused with negative aphereses achieved complete remission and showed a significantly better 5-year PFS (100%) compared to those reinfused with contaminated samples (41%), a very low amount of contamination does not appear to negatively affect outcome, suggesting that determination of a cutoff in the contamination level of harvests could be useful. Results suggest that real-time PCR is superior to Genescan PCR to select transplantable harvests and confirm the ability of Rituximab as an in vivo purging tool for follicular lymphoma.
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- 2003
10. Prospective study of indolent non-follicular non-Hodgkin's lymphoma: validation of Gruppo Italiano per lo studio dei linfomi (GISL) prognostic criteria for watch and wait policy
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Morabito, F., Baldini, L., Stelitano, C., Luminari, Stefano, Frassoldati, A., Merli, F., Colombi, M., Sabbatini, R., Brugiatelli, M., Federico, Massimo, and per lo studio dei linfomi, G. I.
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Multivariate analysis ,Severity of Illness Index ,Disease-Free Survival ,Immunophenotyping ,Lymphoplasmacytic Lymphoma ,Risk Factors ,hemic and lymphatic diseases ,Internal medicine ,Severity of illness ,Humans ,Medicine ,Prospective Studies ,Progression-free survival ,Prospective cohort study ,Survival analysis ,Aged ,Aged, 80 and over ,Analysis of Variance ,80 and over ,Disease Management ,L-Lactate Dehydrogenase ,Lymphoma ,Non-Hodgkin ,Middle Aged ,Prognosis ,Survival Analysis ,business.industry ,Lymphoma, Non-Hodgkin ,Hematology ,medicine.disease ,Surgery ,B symptoms ,medicine.symptom ,business - Abstract
Only recently both the Revised European American Lymphoma (REAL) and World Health Organization (WHO) classifications clearly identified indolent non-follicular non-Hodgkin's lymphoma (NHL) as a distinct group of precise histological entities. Therefore, prognostic models, specifically designed for this NHL subset, are still lacking. In this study, we prospectically evaluated the prognostic criteria proposed by the Gruppo Italiano per lo studio dei linfomi (GISL) to identify patients with an indolent non-progressive clinical course, eligible for a watch and wait policy within this histological subset defined according to stringent criteria of histomorphology and immunophenotype. Fifty-three patients affected with small lymphocytic, marginal zone, lymphoplasmacytic lymphoma and lacking at presentation the following: B symptoms, bulky disease, anemia, thrombocytopenia, diffuse pattern of bone marrow infiltration and short tumor doubling time, were registered in a prospective therapeutic GISL trial and addressed to a watch and wait program. After 41.3 months of median follow-up, the median progression free survival (PFS) was not reached and 73% of cases did not progress. When additional variables were considered, in order to improve the prognostic model, it was evident that LDH level and the number of extranodal sites were of statistical significance in the multivariate analysis. Based on this finding, a prognostic score was devised which was able to further identify a small group of patients more likely to undergo early progression, and thus suitable for immediate treatment. In conclusion, the GISL definition of indolent disease is a reliable tool to design the appropriate therapeutic strategy in this histological setting.
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- 2002
11. Hema e-Chart: Italian Registry for prospective analysis of epidemiology, management and outcome of febrile events in patients with hematological malignancies
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Pagano, L, Caira, M, Nosari, A, Rossi, G, Locatelli, F, Viale, P, Aversa, F, Chart Group Italy:CollaboratorsLevis A, Hema E., Leoni, P, Liso, V, Baccarani, M, Cortellazzo, S, Russo, D, La Nasa, G, Storti, S, Giustolisi, R, Morabito, F, Cuneo, Antonio, Bosi, A, Capalbo, Sf, Cascavilla, N, Ghio, R, Carella, A, Brugiatelli, M, Ciceri, F, Martinelli, G, Morra, E, Pogliani, E, Mettivier, V, Carli, M, Abbadessa, V, Musso, M, Aricò, M, Lazzarino, M, Visani, G, Fioritoni, G, Di Bartolomeo, P, Vallisa, D, Petrini, M, Favre, C, Olivieri, A, Gugliotta, L, Leone, G, Amadori, S, De Rossi, G, De Fabritiis, P, Majolino, I, D'Arco, A, Lauria, F, Mazza, P, Fagioli, F, Gherlinzoni, F, Chesesi, T, Rodeghiero, F., Pagano L, Caira M, Nosari A, Rossi G, Locatelli F, Viale P, Aversa F, Baccarani M, and Hema E-Chart Group Italy.
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medicine.medical_specialty ,Pediatrics ,Myeloid ,Fever ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,hemic and lymphatic diseases ,Epidemiology ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Registries ,Medical diagnosis ,Prospective cohort study ,Multiple myeloma ,Pharmacology ,HAEMATOLOGY ,business.industry ,Incidence ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,FUNGI ,Fungal infection ,Hematological malignancies ,medicine.disease ,Surgery ,Lymphoma ,Settore MED/15 - MALATTIE DEL SANGUE ,Infectious Diseases ,medicine.anatomical_structure ,Italy ,Mycoses ,Oncology ,Hematologic Neoplasms ,business - Abstract
The aim of the study was to create a prospective computerized registry to collect and analyze febrile events, particularly due to fungal infections, in patients with hematological malignancies. A systematic approach that starts from the registration of new diagnosis and complete follow-up can be of help for the study of treatment and evolution of these complications. The software allows several concurrent users to create and manage medical information in a website. Its aim is to improve the speed, quality and integration of information related to subjects with febrile event, ultimately resulting in improving patients' care.Patients included adults and children with acute and chronic myeloid or lymphoid leukemia, Hodgkin's and non-Hodgkin's lymphoma, myelodysplastic syndrome, or multiple myeloma. The registry also included data regarding event onset in hematopoietic stem cell transplants (HSCTs). In order to evaluate the incidence of febrile events, all new diagnoses of hematological malignancy and all HSCTs were reported.The Hema e-Chart can be a very useful network collecting information about febrile events in patients with hematological malignancy and HSCTs. Significant trends and treatment practices are expected to be observed. As enrollment continues, data will be analyzed and published, which will provide valuable information concerning the epidemiology, therapy, and outcome of infectious complications.
12. Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
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Francesco D'Alo', Antonio Pinto, Giovanni Tripepi, Armando Santoro, Pier Luigi Zinzani, Fortunato Morabito, Francesca Ricci, Emanuela Morelli, Luigi Rigacci, Rosaria De Filippi, De Filippi R., Morabito F., Santoro A., Tripepi G., D'Alo F., Rigacci L., Ricci F., Morelli E., Zinzani P.L., Pinto A., De Filippi, R., Morabito, F., Santoro, A., Tripepi, G., D'Alo, F., Rigacci, L., Ricci, F., Morelli, E., Zinzani, P. L., and Pinto, A.
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,Immune Checkpoint Inhibitor ,Programmed Cell Death 1 Receptor ,Antineoplastic Agents ,Overweight ,General Biochemistry, Genetics and Molecular Biology ,Body Mass Index ,Immune checkpoint inhibitors ,Young Adult ,Antineoplastic Agents, Immunological ,Retrospective Studie ,Immune-related adverse events ,Internal medicine ,Immune-related adverse event ,80 and over ,medicine ,Humans ,Adverse effect ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Research ,Incidence (epidemiology) ,General Medicine ,Middle Aged ,Hodgkin Disease ,Settore MED/15 - MALATTIE DEL SANGUE ,Immunological ,Nivolumab ,B symptoms ,Toxicity ,Medicine ,Female ,Underweight ,medicine.symptom ,business ,Body mass index ,Hodgkin lymphoma ,Human - Abstract
Background Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. Methods Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions. Results Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. Conclusions In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic ‘equalizers’ counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.
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- 2021
13. TP53 Mutations with Low Variant Allele Frequency Predict Short Survival in Chronic Lymphocytic Leukemia
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Peter Hillmen, Davide Rossi, Riccardo Bomben, Filippo Vit, Michele Berton, Gabriele Pozzato, Anna Hockaday, Giovanni D'Arena, Jared A. Cohen, Pietro Bulian, Ilaria Cattarossi, Fortunato Morabito, Massimo Degan, Jacopo Olivieri, Gilberto Fronza, Chris Pepper, Francesco Di Raimondo, Anna Schuh, Annalisa Biagi, Jerry Polesel, Antonella Zucchetto, Francesca Rossi, Erika Tissino, Massimo Gentile, Giovanni Del Poeta, Valter Gattei, Francesco Zaja, Paola Nanni, Elena Vendramini, Eva Zaina, Annalisa Chiarenza, Federico Pozzo, Tamara Bittolo, Enrico Santinelli, Tiziana D'Agaro, Paola Varaschin, Alessandra Braida, Bomben, R., Rossi, F. M., Vit, F., Bittolo, T., D'Agaro, T., Zucchetto, A., Tissino, E., Pozzo, F., Vendramini, E., Degan, M., Zaina, E., Cattarossi, I., Varaschin, P., Nanni, P., Berton, M., Braida, A., Polesel, J., Cohen, J. A., Santinelli, E., Biagi, A., Gentile, M., Morabito, F., Fronza, G., Pozzato, G., D'Arena, G., Olivieri, J., Bulian, P., Pepper, C., Hockaday, A., Schuh, A., Hillmen, P., Rossi, D., Chiarenza, A., Zaja, F., Di Raimondo, F., Del Poeta, G., and Gattei, V.
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Oncology ,Cancer Research ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Chronic lymphocytic leukemia ,Variant allele ,Tp53 mutation ,medicine.disease ,Training cohort ,Chemoimmunotherapy ,Internal medicine ,Cohort ,Overall survival ,Medicine ,Small TP53 Mutated sub-clones in CLL ,business ,neoplasms ,Short survival - Abstract
Purpose: In chronic lymphocytic leukemia (CLL), TP53 mutations are associated with reduced survival and resistance to standard chemoimmunotherapy (CIT). Nevertheless, the clinical impact of subclonal TP53 mutations below 10% to 15% variant allele frequency (VAF) remains unclear. Experimental Design: Using a training/validation approach, we retrospectively analyzed the clinical and biological features of TP53 mutations above (high-VAF) or below (low-VAF) the previously reported 10.0% VAF threshold, as determined by deep next-generation sequencing. Clinical impact of low-VAF TP53 mutations was also confirmed in a cohort (n = 251) of CLL treated with fludarabine-cyclophosphamide-rituximab (FCR) or FCR-like regimens from two UK trials. Results: In the training cohort, 97 of 684 patients bore 152 TP53 mutations, while in the validation cohort, 71 of 536 patients had 109 TP53 mutations. In both cohorts, patients with the TP53 mutation experienced significantly shorter overall survival (OS) than TP53 wild-type patients, regardless of the TP53 mutation VAF. By combining TP53 mutation and 17p13.1 deletion (del17p) data in the total cohort (n = 1,220), 113 cases were TP53 mutated only (73/113 with low-VAF mutations), 55 del17p/TP53 mutated (3/55 with low-VAF mutations), 20 del17p only, and 1,032 (84.6%) TP53 wild-type. A model including low-VAF cases outperformed the canonical model, which considered only high-VAF cases (c-indices 0.643 vs. 0.603, P < 0.0001), and improved the prognostic risk stratification of CLL International Prognostic Index. Clinical results were confirmed in CIT-treated cases (n = 552) from the retrospective cohort, and the UK trials cohort. Conclusions: TP53 mutations affected OS regardless of VAF. This finding can be used to update the definition of TP53 mutated CLL for clinical purposes.
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- 2021
14. Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): long-term follow-up analysis of a randomised phase 3, open-label study
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Paola Tacchetti, Lucia Pantani, Francesca Patriarca, Maria Teresa Petrucci, Elena Zamagni, Luca Dozza, Monica Galli, Francesco Di Raimondo, Claudia Crippa, Mario Boccadoro, Simona Barbato, Patrizia Tosi, Franco Narni, Vittorio Montefusco, Nicoletta Testoni, Antonio Spadano, Carolina Terragna, Norbert Pescosta, Giulia Marzocchi, Claudia Cellini, Piero Galieni, Sonia Ronconi, Marco Gobbi, Lucio Catalano, Antonio Lazzaro, Giovanni De Sabbata, Clotilde Cangialosi, Fabrizio Ciambelli, Pellegrino Musto, Francesca Elice, Michele Cavo, Renato Fanin, Roberto Foa', Alessandro Rambaldi, Giuseppe Rossi, Pietro Leoni, Paolo Corradini, Giuseppe Torelli, Giuseppe Fioritoni, Sergio Cortelazzo, Giorgio Lambertenghi Deliliers, Giorgio La Nasa, Alfonso Zaccaria, Paolo De Fabritiis, Nicola Cascavilla, Alberto Bosi, Gianpietro Semenzato, Luigi Gugliotta, Filippo Gherlinzoni, Emanuele Angelucci, Massimo Fabrizio Martelli, Maria Concetta Petti, Giuseppe Leone, Angelo Michele Carella, Fabio Ciceri, Armando Santoro, Felicetto Ferrara, Francesco Nobile, Alfonso Maria D'Arco, Alessandro Levis, Luciano Guardigni, Andrea Gallamini, Pier Paolo Fattori, Sergio Morandi, Dino Amadori, Bruno Rotoli, Salvatore Mirto, Giorgio Paladini, Ruggero Mozzana, Graziella Pinotti, Francesco Rodeghiero, Nicola Cantore, Vincenzo Pavone, Enrico Maria Pogliani, Anna Marina Liberati, Ignazio Majolino, Sergio Amadori, Francesco Lauria, Massimo Aglietta, Giovanni Quarta, Sergio Storti, Fortunato Morabito, Silvana Franca Capalbo, Alessandro Massimo Gianni, Vincenzo Mettivier, Vittorio Rizzoli, Carlo Bernasconi, Giuseppe Visani, Michele Pizzuti, Giacinto La Verde, Giuseppe Avvisati, Maurizio Longinotti, Eugenio Gallo, Franco Dammacco, Domenico Russo, Andrea Bacigalupo, Caterina Musolino, Tacchetti P., Pantani L., Patriarca F., Petrucci M.T., Zamagni E., Dozza L., Galli M., Di Raimondo F., Crippa C., Boccadoro M., Barbato S., Tosi P., Narni F., Montefusco V., Testoni N., Spadano A., Terragna C., Pescosta N., Marzocchi G., Cellini C., Galieni P., Ronconi S., Gobbi M., Catalano L., Lazzaro A., De Sabbata G., Cangialosi C., Ciambelli F., Musto P., Elice F., Cavo M., Fanin R., Foa' R., Rambaldi A., Rossi G., Leoni P., Corradini P., Torelli G., Fioritoni G., Cortelazzo S., Lambertenghi Deliliers G., La Nasa G., Zaccaria A., De Fabritiis P., Cascavilla N., Bosi A., Semenzato G., Gugliotta L., Gherlinzoni F., Angelucci E., Martelli M.F., Petti M.C., Leone G., Carella A.M., Ciceri F., Santoro A., Ferrara F., Nobile F., D'Arco A.M., Levis A., Guardigni L., Gallamini A., Fattori P.P., Morandi S., Amadori D., Rotoli B., Mirto S., Paladini G., Mozzana R., Pinotti G., Rodeghiero F., Cantore N., Pavone V., Pogliani E.M., Liberati A.M., Majolino I., Amadori S., Lauria F., Aglietta M., Quarta G., Storti S., Morabito F., Capalbo S.F., Gianni A.M., Mettivier V., Rizzoli V., Bernasconi C., Visani G., Pizzuti M., La Verde G., Avvisati G., Longinotti M., Gallo E., Dammacco F., Russo D., Bacigalupo A., and Musolino C.
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Phases of clinical research ,Transplantation, Autologous ,Dexamethasone ,Bortezomib ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,GIMEMA-MMY-3006 trial, bortezomib, thalidomide, dexamethasone, VTD, double autologous haematopoietic stem-cell transplantation, multiple myeloma ,Multiple myeloma ,Aged ,Intention-to-treat analysis ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Thalidomide ,Transplantation ,Regimen ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Background: The phase 3 GIMEMA-MMY-3006 trial, which compared bortezomib, thalidomide, and dexamethasone (VTD) combination therapy with thalidomide and dexamethasone (TD) as induction therapy before and consolidation therapy after double autologous haematopoietic stem-cell transplantation (HSCT) for newly diagnosed multiple myeloma, showed the superiority of the triplet regimen over the doublet in terms of increased complete response rate and improved progression-free survival. We report the results from the final analysis of the study. Methods: In this randomised, open-label, phase 3 study, patients aged 18–65 years with previously untreated symptomatic multiple myeloma and a Karnofsky Performance Status of 60% or higher were enrolled at 73 centres in Italy. Patients were randomised (1:1) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily orally for the first 14 days and 200 mg daily thereafter) plus dexamethasone (total 320 mg per cycle; 40 mg on days 1–2, 4–5, 8–9, and 11–12 in the VTD regimen, and 40 mg on days 1–4 and 9–12 in the TD regimen), either alone (TD group) or with bortezomib (1·3 mg/m2 intravenously on days 1, 4, 8, and 11; VTD group). After double autologous HSCT, patients received two 35-day cycles of either the VTD or TD regimen, according to random assignment, as consolidation therapy. The primary outcome was the rate of complete response and near complete response after induction (already reported). In this updated analysis we assessed long-term progression-free survival and overall survival (secondary endpoints of the study) with an extended 10-year median follow-up, and analysed the variables influencing survival. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, NCT01134484. Findings: Between May 10, 2006, and April 30, 2008, 480 patients were enrolled and randomly assigned to receive VTD (241 patients) or TD (239 patients). Six patients withdrew consent before start of treatment. 236 (99 [42%] women) in the VTD group and 238 (102 [43%] women) in the TD group were included in the intention-to-treat analysis. The data cutoff date for this analysis was May 31, 2018. Median follow-up for surviving patients was 124·1 months (IQR 117·2–131·7). The 10-year progression-free survival estimate for patients in the VTD group was 34% (95% CI 28–41) compared with 17% (13–23) for the TD group (hazard ratio [HR] 0·62 [95% CI 0·50–0·77]; p
- Published
- 2020
15. An in-depth evaluation of acalabrutinib for the treatment of mantle-cell lymphoma
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Sara Galimberti, Mohammed Abu-Rayyan, Anna Grazia Recchia, Giovanna Cutrona, Cirino Botta, Moien Atrash, Lucio Morabito, Massimo Gentile, Ernesto Vigna, Mamdouh Skafi, Hamdi Al-Janazreh, Massimo Martino, Fortunato Morabito, Morabito F., Recchia A.G., Vigna E., Botta C., Skafi M., Abu-Rayyan M., Atrash M., Galimberti S., Morabito L., Al-Janazreh H., Martino M., Cutrona G., and Gentile M.
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Acalabrutinib ,BTK ,MCL ,therapy ,Agammaglobulinaemia Tyrosine Kinase ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Benzamides ,Humans ,Lymphoma, Mantle-Cell ,Protein Kinase Inhibitors ,Pyrazines ,Oncology ,medicine.medical_specialty ,Lymphoma ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Bruton's tyrosine kinase ,Pharmacology (medical) ,Lenalidomide ,Pharmacology ,biology ,business.industry ,Bortezomib ,Standard treatment ,General Medicine ,Mantle-Cell ,medicine.disease ,Clinical trial ,chemistry ,030220 oncology & carcinogenesis ,Ibrutinib ,biology.protein ,Mantle cell lymphoma ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Introduction: Regimens involving intensive immuno-chemotherapy, followed by high-dose therapy and autologous stem cell transplant represent the standard treatment for younger fit patients with mantle cell lymphoma (MCL). Targeted approaches (i.e. ibrutinib, bortezomib, and lenalidomide) represent the backbone of therapy for relapsed cases. Areas covered: Acalabrutinib is a novel small molecule with a butynamide moiety specifically designed to irreversibly inhibit Bruton tyrosine kinase (BTK), which is more potent and selective than ibrutinib. Relevant publications have been identified through literature searches using the terms 'mantle cell lymphoma' and 'acalabrutinib'. Expert opinion: Acalabrutinib has been approved for the treatment of relapsed/refractory (RR) MCL patients. To date, clinical trials have reported some adverse effects such as cardiac toxicity or atrial fibrillation. Acalabrutinib in combination with other drugs, either in chemo-containing or chemo-free schedules, represent a valid option for MCL. However, none of the treatment schedules containing BTK inhibitors have been shown to be curative in MCL. Acalabrutinib may ultimately represent an option for patients who are 'fit' and exhibit well-controlled disease, which often characterizes only a limited 'niche' among MCL patients.
- Published
- 2019
16. Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities
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Fortunato Morabito, Ernesto Vigna, Francesco Mendicino, Cirino Botta, Antonino Neri, Pierpaolo Correale, Domenica Ronchetti, Massimo Gentile, Enrica Antonia Martino, Botta C., Mendicino F., Martino E.A., Vigna E., Ronchetti D., Correale P., Morabito F., Neri A., and Gentile M.
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Review ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,tumor immunology ,Elotuzumab ,Multiple myeloma ,RC254-282 ,Isatuximab ,Monoclonal antibodie ,business.industry ,Daratumumab ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,medicine.disease ,Pomalidomide ,anti-cancer immune response ,Thalidomide ,multiple myeloma ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,immunotherapy ,monoclonal antibodies ,business ,Monoclonal gammopathy of undetermined significance ,medicine.drug - Abstract
Simple Summary The growing interest in immunotherapy for the treatment of multiple myeloma demands a deep knowledge of the complex interactions between malignant and immune cells within the bone marrow. Indeed, understanding the cellular and molecular mechanisms underlying this network should represent the basis for the design of novel patient-oriented biological therapeutic approaches. Here, we describe the role of the main immune components of the myeloma niche along disease evolution and their implication in impairing/improving the response to anti-cancer treatments. Additionally, we provided an overview of the potential weakness of this pro-tumor interplay, evidencing novel therapeutic opportunities, which deserve future clinical investigations. Abstract Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients.
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- 2021
17. Survival risk score for real-life relapsed/refractory chronic lymphocytic leukemia patients receiving ibrutinib. A campus CLL study
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Valter Gattei, Gian Matteo Rigolin, Yair Herishanu, Aaron Polliack, Annalisa Chiarenza, Francesca Rossi, Fortunato Morabito, Marzia Varettoni, Paolo Sportoletti, Roberta Murru, Riccardo Bomben, Gianluigi Reda, Giovanni Tripepi, Giacomo Loseto, Luca Laurenti, Graziella D’. Arrigo, Annalisa Biagi, Antonella Zucchetto, Adalgisa Condoluci, Ugo Consoli, Antonio Cuneo, Ilaria Del Giudice, Davide Rossi, Anna Grazia Recchia, Francesco Di Raimondo, Riccardo Moia, Giovanni Del Poeta, Robin Foà, Gianluca Gaidano, Ilaria Scortechini, Vincenzo Fraticelli, Ilaria Angeletti, Daniela Pietrasanta, Angela Rago, Cirino Botta, Marta Coscia, Ernesto Vigna, Francesca Romana Mauro, Massimo Gentile, Gentile M., Morabito F., Del Poeta G., Mauro F.R., Reda G., Sportoletti P., Laurenti L., Coscia M., Herishanu Y., Recchia A.G., Varettoni M., Murru R., Chiarenza A., Condoluci A., Moia R., Pietrasanta D., Loseto G., Consoli U., Scortechini I., Rossi F.M., Zucchetto A., Fraticelli V., Vigna E., Botta C., Tripepi G., Arrigo G.D., Rago A., Angeletti I., Biagi A., Del Giudice I., Bomben R., Rigolin G.M., Rossi D., Di Raimondo F., Gaidano G., Polliack A., Cuneo A., Foa R., and Gattei V.
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Oncology ,Cancer Research ,medicine.medical_specialty ,Survival risk score ,Chronic lymphocytic leukemia ,Treatment outcome ,Antineoplastic Agents ,risk score ,NO ,chemistry.chemical_compound ,relapsed/refractory chronic lymphocytic leukemia ,Antineoplastic Agents, Immunological ,Piperidines ,ibrutinib ,Internal medicine ,medicine ,Humans ,real-life ,Molecular Targeted Therapy ,Chronic ,Protein Kinase Inhibitors ,Framingham Risk Score ,Leukemia ,chronic lymphocytic leukemia ,prognosis ,business.industry ,Adenine ,B-Cell ,Hematology ,medicine.disease ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,prognostic score ,Lymphocytic ,Survival risk score, real-life, relapsed/refractory chronic lymphocytic leukemia, ibrutinib ,Settore MED/15 - MALATTIE DEL SANGUE ,Immunological ,Treatment Outcome ,chemistry ,Ibrutinib ,Relapsed refractory ,business - Published
- 2021
18. Assessment of the 4-factor score: Retrospective analysis of 586 CLL patients receiving ibrutinib. A campus CLL study
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Ilaria Scortechini, Riccardo Moia, Marzia Varettoni, Francesca Romana Mauro, Sara Galimberti, Giovanni Del Poeta, Graziella D'Arrigo, Marta Coscia, Luca Laurenti, Ernesto Vigna, Davide Rossi, Annalisa Biagi, Gianluca Gaidano, Daniele Caracciolo, Riccardo Bomben, Ilaria Angeletti, Gianluigi Reda, Giovanna Cutrona, Daniela Pietrasanta, Gilberto Fronza, Ramona Cassin, Antonino Neri, Aaron Polliack, Annalisa Chiarenza, Yair Herishanu, Fortunato Morabito, Ilaria Del Giudice, Valter Gattei, Francesca Rossi, Roberta Murru, Giovanni Tripepi, Andrea Visentin, Livio Trentin, Antonio Cuneo, Angela Rago, Antonella Zucchetto, Adalgisa Condoluci, Giacomo Loseto, Ugo Consoli, Enrica Antonia Martino, Manlio Ferrarini, Massimo Gentile, Francesco Di Raimondo, Francesco Mendicino, Paolo Sportoletti, Robin Foà, Cirino Botta, Morabito F., Tripepi G., Del Poeta G., Mauro F.R., Reda G., Sportoletti P., Laurenti L., Coscia M., Herishanu Y., Varettoni M., Murru R., Chiarenza A., Visentin A., Condoluci A., Moia R., Pietrasanta D., Loseto G., Consoli U., Scortechini I., Rossi F.M., Zucchetto A., Vigna E., Martino E.A., Mendicino F., Botta C., Caracciolo D., Cassin R., D'Arrigo G., Galimberti S., Rago A., Angeletti I., Biagi A., Del Giudice I., Bomben R., Neri A., Fronza G., Cutrona G., Rossi D., Di Raimondo F., Cuneo A., Gaidano G., Polliack A., Trentin L., Foa R., Ferrarini M., Gattei V., and Gentile M.
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Oncology ,Male ,chronic B cell leukemia ,chronic lymphocytic leukemia ,ibrutinib ,4-factor score ,prognosis ,Datasets as Topic ,Severity of Illness Index ,chemistry.chemical_compound ,Piperidines ,Retrospective analysis ,Multicenter Studies as Topic ,Chronic ,Leukemia ,Hematology ,Middle Aged ,Prognosis ,Lymphocytic ,Progression-Free Survival ,Ibrutinib ,Female ,medicine.medical_specialty ,real-word study ,Factor score ,Antineoplastic Agents ,Adenine ,Aged ,Follow-Up Studies ,Humans ,Leukemia, Lymphocytic, Chronic, B-Cell ,Proportional Hazards Models ,Protein Kinase Inhibitors ,Reproducibility of Results ,Retrospective Studies ,Risk Assessment ,Survival Analysis ,NO ,Internal medicine ,Severity of illness ,medicine ,Progression-free survival ,Survival analysis ,business.industry ,Proportional hazards model ,B-Cell ,Retrospective cohort study ,Settore MED/15 - MALATTIE DEL SANGUE ,chemistry ,business ,chronic lymphocytic leukaemia - Abstract
Not Available
- Published
- 2021
19. Modal Structure and Altered States of Consciousness
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Mario Bottone, Benedetta Muzii, Anna Esposito, Raffaele Sperandeo, Simone D’Andrea, Donatella Di Corrado, Nelson Mauro Maldonato, Maldonato, Nelson Mauro, Bottone, Mario, Muzii, Benedetta, di Corrado, Donatella, Sperandeo, Raffaele, D’Andrea, Simone, Esposito, Anna, Maldonato N.M., Bottone M., Muzii B., di Corrado D., Sperandeo R., D’Andrea S. Esposito A., Esposito A., Faundez-Zanuy M., Morabito F., Pasero E., Maldonato, N. M., Bottone, M., Muzii, B., di Corrado, D., Sperandeo, R., D'Andrea, S., and Esposito, A.
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Structure (mathematical logic) ,Psychopathology ,Consciousne ,media_common.quotation_subject ,Ascending reticular activating system ,Altered state of consciousness ,Modal structure ,medicine.disease ,The Void ,Clinical knowledge ,Phenomenon ,medicine ,Wakefulness ,Consciousness ,Psychology ,Altered state ,Cognitive psychology ,media_common - Abstract
Although it is a familiar experience for everyone, in the vast majority of cases we discover the importance of consciousness only when in front of someone who no longer appears to possess it: someone ‘absent’, with their eyes fixed in the void, while the heart beats vigorously and their muscle tone is intact; or a patient with a psycho-organic syndrome or brain trauma, who is awake, even alert, but no longer in contact with the surrounding environment. Despite the fact that millions of people around the world enter and leave the state of consciousness every day, neurophysiological and clinical knowledge about consciousness is still far from forming a coherent scientific corpus. In fact, nowadays, there is no general shared definition of an altered state of consciousness. In this paper we propose a structured model of the phenomenon of consciousness, viewed as a multivariate combination of independent factors, which includes the variations and transitions of consciousness from a normal state of wakefulness to a psychopathological condition (with discrete deviations in subjective experience), and to severe clinical-neurological pictures.
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- 2021
20. Testing graph robustness indexes for eeg analysis in alzheimer’s disease diagnosis
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Giuseppe M. L. Sarné, Domenico Rosaci, Nadia Mammone, Fabio La Foresta, Serena Dattola, Francesco Carlo Morabito, Dattola, S, Mammone, N, Morabito, F, Rosaci, D, Sarne, G, and Foresta, F
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medicine.medical_specialty ,TK7800-8360 ,Computer Networks and Communications ,Kirchhoff index ,Disease ,Brain network analysi ,Audiology ,03 medical and health sciences ,0302 clinical medicine ,Robustness (computer science) ,medicine ,Dementia ,Electrical and Electronic Engineering ,Randić index ,030304 developmental biology ,0303 health sciences ,Eeg analysis ,business.industry ,Functional connectivity ,Graph theory ,Connection density index ,medicine.disease ,ELORETA ,Hardware and Architecture ,Control and Systems Engineering ,Signal Processing ,Graph (abstract data type) ,brain network analysis ,Electronics ,business ,030217 neurology & neurosurgery - Abstract
Alzheimer’s Disease (AD) is an incurable neurodegenerative disorder which mainly affects older adults. An early diagnosis is essential because medical treatments can slow down the progression of the disease only if provided during the first stage, called Mild Cognitive Impairment (MCI). Starting from the study of electroencephalografic signals, brain functional connectivity analyses can be performed with the support of the graph theory. In particular, the purpose of this work is to verify the performances of three indexes, typically adopted to evaluate the graph robustness, in order to estimate the functional connectivity for three groups of subjects: healthy controls and people affected by dementia at two different stages (MCI and AD). The results obtained by the Connection Density Index, the Randić Index, and a normalized version of the Kirchhoff Index revealed a higher robustness in the brain networks of healthy people, followed by MCI and, finally, by AD patients, consistent with the hallmarks of Alzheimer’s disease. The statistical analysis showed that there is a significant difference between controls and AD for all three indexes. Finally, all three indexes were compared, revealing that the the Randić Index outperformed the other two indexes. These preliminary outcomes will be exploited to address further in-depth and time-expensive analyses for improving the diagnosis of Alzheimer’s disease.
- Published
- 2021
21. Elotuzumab, lenalidomide, and dexamethasone as salvage therapy for patients with multiple myeloma: Italian, multicenter, retrospective clinical experience with 300 cases outside of controlled clinical trials
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Nicola Cascavilla, Monica Galli, Mario Boccadoro, Dominella Gangemi, Silvia Mangiacavalli, Massimo Offidani, Anna Grazia Recchia, Elena Zamagni, Angelo Belotti, Alessandra Pompa, Claudio Cerchione, Giuseppina Uccello, Paola Curci, Catello Califano, Concetta Conticello, Elena Rossi, Maria Teresa Petrucci, Valerio De Stefano, Giovanni Tripepi, Ugo Consoli, Enrico Attingenti, Marino Brunori, Stelvio Ballanti, Clelia Criscuolo, Nicola Giuliani, Michele Cavo, Renato Zambello, Vincenzo Ludovico Fraticelli, Giorgina Specchia, Angela Bonalumi, Francesca Patriarca, Nicola Di Renzo, Alessandra Lombardo, Salvatore Palmieri, Elisabetta Antonioli, Cirino Botta, Agostina Siniscalchi, Raffaella Stocchi, Barbara Gamberi, Ferdinando Frigeri, Massimo Gentile, Giuseppe Mele, Ernesto Vigna, Pellegrino Musto, Donatella Vincelli, Silvana Capalbo, Annalisa Pitino, Sara Bringhen, Daniele Derudas, Francesco Di Raimondo, Massimo Martino, Roberto Ria, Alfredo Gagliardi, Gianpaolo Marcacci, Fortunato Morabito, Stefano Rocco, Gentile M., Specchia G., Derudas D., Galli M., Botta C., Rocco S., Conticello C., Califano C., Giuliani N., Mangiacavalli S., Attingenti E., Lombardo A., Brunori M., Rossi E., Antonioli E., Ria R., Zambello R., Di Renzo N., Mele G., Marcacci G., Musto P., Capalbo S., Cascavilla N., Cerchione C., Belotti A., Criscuolo C., Uccello G., Curci P., Vigna E., Fraticelli V., Vincelli D., Bonalumi A., Siniscalchi A., Stocchi R., Martino M., Ballanti S., Gangemi D., Gagliardi A., Gamberi B., Pompa A., Recchia A.G., Tripepi G., Pitino A., Frigeri F., Consoli U., Bringhen S., Zamagni E., Patriarca F., De Stefano V., Di Raimondo F., Palmieri S., Petrucci M.T., Offidani M., Boccadoro M., Cavo M., and Morabito F.
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Oncology ,medicine.medical_specialty ,Elotuzumab, lenalidomide, dexamethasone, salvage therapy, multiple myeloma ,Salvage therapy ,Antibodies, Monoclonal, Humanized ,Antibodies ,Dexamethasone ,Efficacy ,Internal medicine ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Elotuzumab ,Letters to the Editor ,Elotuzumab, lenalidomide, dexamethasone, multiple myeloma ,Humanized ,Lenalidomide ,Multiple myeloma ,Retrospective Studies ,Salvage Therapy ,business.industry ,Retrospective cohort study ,Hematology ,medicine.disease ,Clinical trial ,Italy ,Multiple Myeloma ,business ,medicine.drug - Abstract
No abstract available
- Published
- 2021
22. Treatment of Lenalidomide Exposed or Refractory Multiple Myeloma: Network Meta-Analysis of Lenalidomide-Sparing Regimens
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Ernesto Vigna, Fortunato Morabito, Cirino Botta, Giovanni Martinelli, Francesco Mendicino, Enrica Antonia Martino, Concetta Conticello, Alessandra Romano, Massimo Gentile, Giuseppe Antonio Palumbo, Claudio Cerchione, Francesco Di Raimondo, Botta C, Martino EA, Conticello C, Mendicino F, Vigna E, Romano A, Palumbo GA, Cerchione C, Martinelli G, Morabito F, Di Raimondo F, and Gentile M
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Oncology ,Cancer Research ,medicine.medical_specialty ,Opinion ,lenalidomide ,lcsh:RC254-282 ,chemistry.chemical_compound ,Internal medicine ,medicine ,Lenalidomide ,Isatuximab ,carfilzomib ,Bortezomib ,business.industry ,network meta analysis ,bortezomib ,Daratumumab ,Refractory Multiple Myeloma ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,daratumumab ,Carfilzomib ,myeloma ,chemistry ,Meta-analysis ,business ,medicine.drug ,isatuximab - Abstract
Over the past 10 years, the treatment of multiple myeloma (MM) dramatically changed due to the introduction of a number of new agents and combination regimens both in the frontline and in the relapsed/refractory setting. Currently, at least 11 classes of therapeutic agents, including steroids, alkylators (melphalan and cyclophosphamide), proteasome inhibitors (PI: bortezomib, carfilzomib, ixazomib), immunomodulatory agents (thalidomide, lenalidomide, pomalidomide), monoclonal antibodies (mAbs: elotuzumab, daratumumab), HDAC-inhibitors (panobinostat), BCL2 inhibitors (venetoclax), selective inhibitors of nuclear export (selinexor), drug-conjugated mAbs (belantamab mafodotin), bispecific agents and CAR-T, are approved (or are going to be approved) alone or in different combinations for the treatment of this disease, while few or no data are available to guide the therapeutic strategy to adopt at diagnosis or relapse (1). The choice of the treatment at relapse (2), in particular, poses particular challenges, and is currently dependent on patients (age, comorbidities, fitness, renal impairment, frailty) and disease characteristics (aggressive vs biochemical relapse, cytogenetics, presence of extra-medullary disease), previous treatments (classes of agents, duration of response, progression while on therapy), regional drug access (approval of combinations, reimbursement, costs) and, finally, patient’s choice. Unfortunately, there is a lack of trials specifically designed to help in this choice, and often, pre-planned subgroup analyses, do not include a sufficient number of patients to reach statistical evidence. Recently, since lenalidomide is progressively becoming the preferred one-line option to treat MM patients (and often, it is administered until progression), the choice of the treatment to be offered at relapse should be carefully evaluated. Interestingly, it has been reported that the longest prior lenalidomide treatment duration (>12 months) and IMiD-free interval (>18 months) could positively impact patients’ outcome (3), making the choice of a lenalidomide-sparing regimen of particular interest in this setting. On the bases of these premises, we performed a systematic review and a frequentist network meta-analysis in R [by using the netmeta package (4)] comparing direct and indirect evidence on the efficacy of seven different lenalidomide-sparing regimens (bortezomib-dexamethasone, VD; daratumumab-VD, DVD; carfilzomib-D, KD; daratumumab-KD, KdD; pomalidomide-VD, PVD; isatuximab-KD, IKD; selinexor-VD, SVD) in lenalidomide-exposed and lenalidomide-refractory patients, to provide statistical evidence to support clinical decision making
- Published
- 2020
23. Long-Term Remission Achieved by Ponatinib and Donor Lymphocytes Infusion in a Ph+ Acute Lymphoblastic Leukemia Patient in Molecular Relapse After Allogenic Stem Cell Transplant and Dasatinib: A Case Report
- Author
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Cirino Botta, Nadia Caruso, Sabrina Bossio, Francesca Storino, Giuseppe Console, Massimo Martino, Francesco Mendicino, Eugenio Lucia, Rosellina Morelli, Pierpaolo Correale, Fortunato Morabito, Massimo Gentile, Ernesto Vigna, Botta C., Caruso N., Bossio S., Storino F., Console G., Martino M., Mendicino F., Lucia E., Morelli R., Correale P., Morabito F., Gentile M., and Vigna E.
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cancer Research ,medicine.medical_treatment ,T lymphocytes ,Case Report ,Hematopoietic stem cell transplantation ,lcsh:RC254-282 ,Donor lymphocyte infusion ,bone marrow microenviroment ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,acute lymhoblastic leukemia ,Internal medicine ,hemic and lymphatic diseases ,T lymphocyte ,medicine ,ponatinib ,business.industry ,Ponatinib ,Donor Lymphocytes ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Dasatinib ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,donor lymphocyte infusion (DLI) ,Bone marrow ,Stem cell ,business ,CD8 ,medicine.drug - Abstract
Currently, the prognosis of Ph+ acute lymphoblastic leukemia (Ph+ ALL) patients relapsing after an allogenic hematopoietic stem cell transplantation (allo-SCT) remains poor, with few therapeutic options available. Here we present the case of a 32 years old patient with dasatinib-resistant post-transplant molecular relapse of ALL, who received, as second-line therapy, the combination of ponatinib and donor lymphocyte infusion (DLI). The therapy was safe and the patient achieved a sustained minimal residual disease negative disease, still ongoing after 22 months, which was accompanied by several changes in the immune populations distribution within the bone marrow (i.e., the increase in the CD8/CD4 lymphocytes ratio). Our report provides evidence of the efficacy of the third generation TKI inhibitor ponatinib in combination with DLI as second line therapy for Ph+ ALL relapsing after an allo-SCT.
- Published
- 2020
24. A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia
- Author
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Annalisa Chiarenza, Valter Gattei, Agostino Steffan, Neil E. Kay, Giovanni D'Arena, Francesca Rossi, Christopher Fegan, Davide Rossi, Fortunato Morabito, Chris Pepper, Jerry Polesel, Massimo Degan, Kari G. Rabe, Riccardo Bomben, Manlio Ferrarini, Enrico Santinelli, Jared A. Cohen, Lodovico Terzi-di-Bergamo, Francesco Di Raimondo, Antonino Neri, Gabriele Pozzato, Luca Laurenti, Antonella Zucchetto, Massimo Gentile, Idanna Innocenti, Giovanna Cutrona, Sameer A. Parikh, Giovanni Del Poeta, Francesco Zaja, Cohen, Ja, Rossi, Fm, Zucchetto, A, Bomben, R, Terzi-di-Bergamo, L, Rabe, Kg, Degan, M, Steffan, A, Polesel, J, Santinelli, E, Innocenti, I, Cutrona, G, D'Arena, G, Pozzato, G, Zaja, F, Chiarenza, A, Rossi, D, Di Raimondo, F, Laurenti, L, Gentile, M, Morabito, F, Neri, A, Ferrarini, M, Fegan, Cd, Pepper, Cj, Del Poeta, G, Parikh, Sa, Kay, Ne, and Gattei, V.
- Subjects
Oncology ,medicine.medical_specialty ,Prognostic variable ,Chronic lymphocytic leukemia ,Concordance ,Recursive partitioning ,Gene mutation ,Immunophenotyping ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Chronic Lymphocytic Leukemia ,Cytogenetics and Molecular Genetics ,business.industry ," ,Hematology ,Articles ,medicine.disease ,Prognosis ,Settore MED/15 ,Leukemia, Lymphocytic, Chronic, B-Cell ,United Kingdom ,Chromosome 17 (human) ,Settore MED/15 - MALATTIE DEL SANGUE ,Italy ,Mutation ,RC0267 ,business ,Trisomy ,Laboratories ,030215 immunology ,Cohort study - Abstract
We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count>32.0x103/microliter, 1 point. Low, intermediate and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144/395/540/322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era.
- Published
- 2019
25. Effects of Gender and Luminance Backgrounds on the Recognition of Neutral Facial Expressions
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Gennaro Cordasco, Vincenzo Capuano, Marcos Faundez-Zanuy, Mauro Maldonato, Filomena Scibelli, Anna Esposito, Springer Science and Business Media Deutschland GmbH, Capuano, Vincenzo, Cordasco, Gennaro, Scibelli, Filomena, Maldonato, Mauro, Faundez Zanuy, Marco, Esposito, Anna, Faundez-Zanuy, Marco, and Esposito A., Faudez-Zanuy M., Morabito F., Pasero E.
- Subjects
Emotion ,Facial expression ,medicine.medical_specialty ,Socio-cultural influence ,Computer Science (all) ,Audiology ,Luminance ,Emotional recognition ,Gender effect ,Decision Sciences (all) ,Emotion perception ,medicine ,Neutral facial expression ,Psychology - Abstract
In this study we challenged the universal view of facial emotion perception evaluating the effects of gender and different luminance backgrounds on the recognition accuracy of neutral facial expressions. To this aim, we applied the Ekman standard paradigm for assessing the human ability to decode neutral facial expressions reproduced on black, white and grey backgrounds and portrayed by male and female actors. The exploited stimuli consisted of 10 different neutral faces (5 females) selected from the Dutch Radboud database (Langner et al. Cogn Emot, 2010 [21]) where luminance backgrounds were changed in black, grey and white. The resulted 30 stimuli were assessed by 31 subjects (16 females) who were asked to tag each of them with one of the six primary emotion labels. The data analysis demonstrates a significant gender effect where neutral male faces are less accurately decoded than females ones. On the other hand, no effects of luminance backgrounds have been identified.
- Published
- 2017
26. microRNAome Expression in Chronic Lymphocytic Leukemia: Comparison with Normal B-cell Subsets and Correlations with Prognostic and Clinical Parameters
- Author
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Serena Matis, Cristian Bassi, Massimo Negrini, Sonia Fabris, Anna Grazia Recchia, Gian Matteo Rigolin, Manuela Ferracin, Monica Colombo, Antonino Neri, Barbara Zagatti, Lucilla D'Abundo, Giandomenico Russo, Fortunato Morabito, George A. Calin, Luca Agnelli, Manlio Ferrarini, Elena Saccenti, Sabrina Bossio, Daniele Reverberi, Marta Lionetti, Massimo Gentile, Pierfrancesco Tassone, Silvia Sabbioni, Giovanna Cutrona, Negrini M, Cutrona G, Bassi C, Fabris S, Zagatti B, Colombo M, Ferracin M, D'Abundo L, Saccenti E, Matis S, Lionetti M, Agnelli L, Gentile M, Recchia AG, Bossio S, Reverberi D, Rigolin G, Calin GA, Sabbioni S, Russo G, Tassone P, Morabito F, Ferrarini M, and Neri A.
- Subjects
Cancer Research ,tumor suppressor ,Immunoglobulin Heavy Chain ,Chronic lymphocytic leukemia ,B-Lymphocyte Subsets ,Trisomy ,Disease ,Biology ,medicine.disease_cause ,Chromosome Aberration ,survival ,NO ,immune system diseases ,hemic and lymphatic diseases ,microRNA ,CLL patients, profiling reveals, tumor suppressor, down regulation, 17p deletion, mir-34a, cancer, mir29, survival ,medicine ,Chromosomes, Human ,Humans ,cancer ,profiling reveals ,Cells, Cultured ,In Situ Hybridization, Fluorescence ,B cell ,B-Lymphocyte Subset ,Chromosome Aberrations ,mir-34a ,Mutation ,Cancer ,MicroRNA ,mir29 ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,17p deletion ,CLL patients ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,medicine.anatomical_structure ,Oncology ,Immunology ,Disease Progression ,Immunoglobulin Heavy Chains ,IGHV@ ,down regulation ,Human - Abstract
Purpose: Despite its indolent nature, chronic lymphocytic leukemia (CLL) remains an incurable disease. To establish the potential pathogenic role of miRNAs, the identification of deregulated miRNAs in CLL is crucial. Experimental Design: We analyzed the expression of 723 mature miRNAs in 217 early-stage CLL cases and in various different normal B-cell subpopulations from tonsils and peripheral blood. Results: Our analyses indicated that CLL cells exhibited a miRNA expression pattern that was most similar to the subsets of antigen-experienced and marginal zone–like B cells. These normal subpopulations were used as reference to identify differentially expressed miRNAs in comparison with CLL. Differences related to the expression of 25 miRNAs were found to be independent from IGHV mutation status or cytogenetic aberrations. These differences, confirmed in an independent validation set, led to a novel comprehensive description of miRNAs potentially involved in CLL. We also identified miRNAs whose expression was distinctive of cases with mutated versus unmutated IGHV genes or cases with 13q, 11q, and 17p deletions and trisomy 12. Finally, analysis of clinical data in relation to miRNA expression revealed that miR26a, miR532-3p, miR146-5p, and miR29c* were strongly associated with progression-free survival. Conclusion: This study provides novel information on miRNAs expressed by CLL and normal B-cell subtypes, with implication on the cell of origin of CLL. In addition, our findings indicate a number of deregulated miRNAs in CLL, which may play a pathogenic role and promote disease progression. Collectively, this information can be used for developing miRNA-based therapeutic strategies in CLL. Clin Cancer Res; 20(15); 4141–53. ©2014 AACR.
- Published
- 2014
27. Analyzing correlations between personality disorders and frontal functions: A pilot study
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Anna Esposito, Mauro Maldonato, Silvia Dell'Orco, Raffaele Sperandeo, Sperandeo, R, Esposito, A, Maldonato, N.M., Dell'Orco, S., Bassis S., Esposito A., Morabito F., Pasero E., Sperandeo, Raffaele, Esposito, Anna, Maldonato, Mauro, Dell’Orco, Silvia, and Bassis et al
- Subjects
Frontal lobe hypo-functioning ,Personality disorder ,media_common.quotation_subject ,Personality dimensional model ,Computer Science (all) ,Neuropsychology ,medicine.disease ,Executive functions ,Personality disorders ,030227 psychiatry ,Developmental psychology ,03 medical and health sciences ,0302 clinical medicine ,Frontal lobe ,Executive function ,Decision Sciences (all) ,medicine ,Personality ,Abnormality ,Psychology ,Biological basis of personality ,030217 neurology & neurosurgery ,Psychopathology ,media_common ,Clinical psychology - Abstract
This paper reports the results of an open cross-sectional study in which socio-demographic, clinical, psychopathological and neuropsychological features of outpatients—who consecutively enter for treatments in a private service of psychiatry and psychotherapy—are examined. The involved participants (63 subjects, 24 males and 39 females aged from 18 to 66, mean age 34 years) were assessed for personality disorders (PDs) by administering the Structured Clinical Interview for Diagnosis of axis II disorders (SCID-II) and for frontal lobe hypo-functioning activities by administering the Frontal Assessment Battery (FAB). 21 subjects reached a FAB total score less than 13.5, indicating the presence of frontal function deficits. 21 subjects had a diagnosis of Personality Disorder (PD). The remaining 42 subjects did not meet sufficient criteria for any diagnosis of PD even though they showed one or more typical PD symptoms. It was found that the PD syndromic diagnosis did not significantly correlate with frontal functions deficits, while some PD symptoms (such as abnormal behavior, emotional experiences and pathological cognitive processes) correlated negatively with the FAB total scores and therefore with a frontal lobe hypo-functioning. These significant negative correlations suggest that PD symptoms have more ecological value than the DSM V diagnostic categories confirming their artificial nature and uselessness for clinical practices.
- Published
- 2016
28. Aspirin, Warfarin, or Enoxaparin Thromboprophylaxis in Patients With Multiple Myeloma Treated With Thalidomide: A Phase III, Open-Label, Randomized Trial
- Author
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Claudia Crippa, Alessandra Romano, Michele Cavo, Francesca Elice, Roberto Marasca, Mario Boccadoro, Massimo Offidani, Renato Zambello, Claudia Cellini, Valeria Magarotto, Vincenzo Callea, Monica Galli, Claudia Polloni, Patrizia Tosi, Angelo Michele Carella, Giulia Benevolo, Elena Zamagni, Andrea Evangelista, Fabiana Gentilini, Stefano Pulini, Antonio Palumbo, Vittorio Montefusco, Sara Bringhen, Chiara Nozzoli, Davide Rossi, Norbert Pescosta, Roberto Ria, Paola Tacchetti, Francesca Patriarca, Luca Baldini, Tommaso Caravita, Fortunato Morabito, Palumbo A., Cavo M., Bringhen S., Zamagni E., Romano A., Patriarca F., Rossi D., Gentilini F., Crippa C., Galli M., Nozzoli C., Ria R., Marasca R., Montefusco V., Baldini L., Elice F., Callea V., Pulini S., Carella A.M., Zambello R., Benevolo G., Magarotto V., Tacchetti P., Pescosta N., Cellini C., Polloni C., Evangelista A., Caravita T., Morabito F., Offidani M., Tosi P., and Boccadoro M.
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Male ,Cancer Research ,medicine.medical_specialty ,Time Factors ,multiple myeloma ,thrombosis ,prophylaxis ,medicine.drug_class ,Low molecular weight heparin ,Antineoplastic Agents ,Hemorrhage ,Risk Assessment ,Sudden death ,Fibrinolytic Agents ,MULTIPLE MYELOMA ,Risk Factors ,Thromboembolism ,Internal medicine ,Multicenter trial ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Enoxaparin ,THROMBOPROPHYLAXIS ,Contraindication ,Aged ,wafarin ,Aspirin ,business.industry ,Warfarin ,Anticoagulants ,Middle Aged ,Thalidomide ,Surgery ,ASPIRIN ,Treatment Outcome ,Italy ,Oncology ,Cardiovascular Diseases ,Female ,business ,Enoxaparin sodium ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
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.
- Published
- 2011
29. Immunoreactivity for cyclin D1 is a reliable marker of gene aberration in plasma cell myeloma but does not specify patients prognosis
- Author
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Francesco Bertoni, Elena Sabattini, Sonia Fabris, Liliana Calabrese, Francesco Bertolini, Giovanni Martinelli, Giuseppe Viale, Alessandra Alietti, Antonino Neri, Alberto Agazzi, Luca Agnelli, Paola Rafaniello Raviele, Giorgio Lambertenghi-Deliliers, Luca Bottiglieri, Luca Baldini, Stefano Pileri, Daniele Laszlo, Patrick Maisonneuve, Fortunato Morabito, Silvano Bosari, Giancarlo Pruneri, Pruneri G, Alietti A, Agnelli L, Morabito F, Laszlo D, Calabrese L, Fabris S, Bertolini F, Agazzi A, Bottiglieri L, Raviele PR, Baldini L, Pileri S, Sabattini E, Bosari S, Maisonneuve P, Lambertenghi-Deliliers G, Bertoni F, Martinelli G, Viale G, and Neri A.
- Subjects
Adult ,Aged, 80 and over ,Male ,Cancer Research ,business.industry ,Hematology ,Middle Aged ,Prognosis ,Immunohistochemistry ,Survival Analysis ,Translocation, Genetic ,Cyclin D1 ,Oncology ,Cyclin D ,Cyclins ,Plasma Cell Myeloma ,Biomarkers, Tumor ,Cancer research ,Humans ,Medicine ,Female ,Multiple Myeloma ,business ,Gene ,Aged - Published
- 2008
30. B cell chronic lymphocytic leukaemia/small lymphocytic lymphoma: role of ZAP70 determination on bone marrow biopsy specimens
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Cristina Campidelli, Rocio Orduz, Simona Zupo, Giovanna Cutrona, Vincenzo Callea, Pier Luigi Zinzani, Manlio Ferrarini, Elena Sabattini, Stefano Pileri, Fortunato Morabito, Sabattini E, Orduz R, Campidelli C, Zinzani PL, Callea V, Zupo S, Cutrona G, Morabito F, Ferrarini M, and Pileri S.
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Biopsy ,Chronic lymphocytic leukemia ,Blotting, Western ,Immunoglobulin Variable Region ,Pathology and Forensic Medicine ,Immunoenzyme Techniques ,Bone Marrow ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Aged, 80 and over ,ZAP-70 Protein-Tyrosine Kinase ,biology ,medicine.diagnostic_test ,ZAP70 ,General Medicine ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Leukemia ,medicine.anatomical_structure ,Mutation ,biology.protein ,Immunohistochemistry ,Immunoglobulin heavy chain ,Original Article ,Female ,Bone marrow ,Antibody ,Immunoglobulin Heavy Chains - Abstract
Background: The course of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) partly depends on the mutational status of the variable region of immunoglobulin heavy chain genes (IgV H ), which defines two subgroups of tumours: mutated and unmutated. The expression of zeta-associated protein 70 (ZAP70) is significantly associated with the more aggressive unmutated forms. Aims: To assess the feasibility of the ZAP70 immunohistochemical test on bone-marrow biopsy (BMB) specimens and to compare the results with those of western blotting (WB) and IgV H mutational status assessed on neoplastic cells from peripheral blood. Methods: 26 patients with CLL/SLL detected on BMB and with known IgV H mutational status were selected. ZAP70 was determined by immunohistochemistry (IHC) comparing three antibodies from different sources (Upstate, Cell Signaling, Santa Cruz, California, USA) and two different methods (APAAP and EnVision + ). In 23 cases, ZAP70 WB results were also available. Results: ZAP70 determination on BMB specimens turned out to be easily feasible with routine procedures with reagents from Upstate and Cell Signaling. The results were concordant with those obtained with WB and mutational status analysis in >80% of the cases with both reagents. Three of four discordant cases were mutated/ZAP70 positive, with two staining weakly for ZAP70 on both WB and IHC. Conclusions: The study confirms the role of ZAP70 as a possible surrogate of mutational status and emphasises its application in routine diagnostics; it discloses a small subset of discordant cases (mutated/ZAP70 weakly positive) that clinically cluster with the more favourable forms.
- Published
- 2007
31. Bendamustine in combination with Ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial
- Author
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Daniele Vincenti, Nicola Cascavilla, Francesca Romana Mauro, Agostino Cortelezzi, Francesco Zaja, Antonino Neri, Marco Gobbi, Mariarita Sciumè, Anna Marina Liberati, Davide Rossi, Anna Guarini, Sonia Fabris, Giuseppe Gritti, Marco Vignetti, Fortunato Morabito, Sergio Storti, Robin Foà, Gianluigi Reda, Diana Giannarelli, Emanuele Angelucci, Roberto Marasca, Alfonso Piciocchi, Luca Laurenti, Antonio Cuneo, Annalisa Chiarenza, L. Orsucci, Cortelezzi, A, Sciumè, M, Liberati, Am, Vincenti, D, Cuneo, A, Reda, G, Laurenti, L, Zaja, Francesco, Marasca, R, Chiarenza, A, Gritti, G, Orsucci, L, Storti, S, Angelucci, E, Cascavilla, N, Gobbi, M, Mauro, Fr, Morabito, F, Fabris, S, Piciocchi, A, Vignetti, M, Neri, A, Rossi, D, Giannarelli, D, Guarini, A, Foà, R., Liberati, A, Zaja, F, Mauro, F, and Foà, R
- Subjects
Male ,Cancer Research ,Chronic lymphocytic leukemia ,Gastroenterology ,chemistry.chemical_compound ,Recurrence ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,Bendamustine Hydrochloride ,Chronic ,Relapse ,Nitrogen Mustard Compound ,Leukemia ,Hematology ,Refractory CLL ,Antibodies, Monoclonal ,Lymphocytic ,Oncology ,Nitrogen Mustard Compounds ,Bendamustine ,Toxicity ,bendamustine ,ofatumumab ,chronic lymphocytic leukemia ,relapse ,Female ,Refractory Chronic Lymphocytic Leukemia ,Human ,medicine.drug ,medicine.medical_specialty ,Author Keywords:bendamustine, ofatumumab, chronic lymphocytic leukemia, relapse KeyWords Plus:FLUDARABINE PLUS CYCLOPHOSPHAMIDE, INDEPENDENT PREDICTOR, PROGRESSION-FREE, RITUXIMAB, MUTATIONS, THERAPY, SURVIVAL, QUANTIFICATION, CHLORAMBUCIL, EXPRESSION ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Ofatumumab ,Antibodies ,NO ,Internal medicine ,medicine ,Humans ,Aged ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,B-Cell ,Leukemia, Lymphocytic, Chronic, B-Cell ,medicine.disease ,Surgery ,Settore MED/15 - MALATTIE DEL SANGUE ,Anesthesiology and Pain Medicine ,chemistry ,INGLESE ,business - Abstract
We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m 2) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features. © 2014 Macmillan Publishers Limited.
- Published
- 2014
32. The Ascending Reticular Activating System: The common root of consciousness and attention
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Mauro Maldonato, aa.vv., Bassis S., Esposito A., Morabito F., and Maldonato, Mauro
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Consciousne ,media_common.quotation_subject ,Thalamus ,Central nervous system ,Ascending reticular activating system ,Computer Science (all) ,High oscillatory frequency ,Biology ,Reticular formation ,Spinal cord ,Alertness ,medicine.anatomical_structure ,Decision Sciences (all) ,medicine ,Wakefulness ,Attention ,Reticular activating system ,Neuroscience ,Alertne ,Vigilance (psychology) ,media_common - Abstract
In the organization of the central nervous system the role of Ascending Reticular Activating System (ARAS) – comprising the reticular formation, thalamus and thalamo-cortical system of bi-directional projection which governs the activities of wakefulness and vigilance – does not correspond to a hierarchical superiority with respect to the cerebral hemispheres. The ARAS is not limited to the brain stem: it projects upwards towards the cerebral hemispheres and downwards towards the spinal cord. Its functions are much more complex than simple cortical desynchronization, even though this is essential in the state of alertness and attention. Its thalamo-cortical projections, which are a-specific with a high oscillatory frequency, are fundamental for some essential functions of consciousness.
- Published
- 2014
33. Deciding with (or without) the Future in Mind: Individual Differences in Decision-Making
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Ivana Baldassarre, Olimpia Matarazzo, Giovanna Nigro, Marina Cosenza, AA.VV., Bassis,S. Esposito,A., & Morabito, F. C. (Eds.), Cosenza, Marina, Matarazzo, Olimpia, Baldassarre, I, and Nigro, Giovanna
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media_common.quotation_subject ,Decision-making, Impulsivity, Risk-taking, Future orientation ,Regression analysis ,Ambiguity ,Impulsivity ,Iowa gambling task ,Task (project management) ,Barratt Impulsiveness Scale ,Consideration of future consequences ,Scale (social sciences) ,medicine ,medicine.symptom ,Psychology ,Clinical psychology ,media_common - Abstract
The aim of this study was to examine the influence of propensity to risk taking, impulsivity, and present versus future orientation in decision-making under ambiguity. One hundred and four healthy adults were administered the computer versions of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART). They then completed the Barratt Impulsiveness Scale (BIS-11) and the Consideration of Future Consequences Scale (CFC-14). Results indicated that high scores on the BIS-11 Non-Planning impulsivity scale, the CFC-14 Immediate scale, and the BART result in poorer performance on the IGT. In addition, the results of regression analysis showed also that the BART total score was the most powerful predictor of performance on the IGT. The study revealed that individuals who are more prone to risk, less likely to plan ahead carefully, and more oriented to the present, rather than to the future, performed worse on the IGT.
- Published
- 2014
34. Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia
- Author
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Giuseppe Pietrantuono, Giovanni D'Arena, Roberto Guariglia, F. Di Raimondo, Massimo Offidani, Paola Omedè, Attilio Olivieri, Nicola Cascavilla, Tommaso Caravita, Roberto Mina, Pellegrino Musto, Katia Todoerti, Maide Cavalli, Nunzio Filardi, Mario Boccadoro, Fortunato Morabito, Francesco Nobile, Sara Bringhen, Antonio Palumbo, Luca Agnelli, Maria Carmen Martorelli, Oreste Villani, Antonino Neri, Vittorio Simeon, G. Mansueto, A. Falcone, Giulia Benevolo, Rosa Lerose, M.T. Petrucci, Anna Levi, Musto, P, Simeon, V, Martorelli, M C, Petrucci, M T, Cascavilla, N, Di Raimondo, F, Caravita, T, Morabito, F, Offidani, M, Olivieri, A, Benevolo, G, Mina, R, Guariglia, R, D'Arena, G, Mansueto, G, Filardi, N, Nobile, F, Levi, A, Falcone, A, Cavalli, M, Pietrantuono, G, Villani, O, Bringhen, S, Omedè, P, Lerose, R, Agnelli, L, Todoerti, K, Neri, A, Boccadoro, M, and Palumbo, A
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Newly diagnosed ,Dexamethasone ,Leukemia, Plasma Cell ,Internal medicine ,medicine ,Humans ,Lenalidomide ,Aged ,Plasma cell leukemia ,Aged, 80 and over ,Chemotherapy ,business.industry ,Low dose ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Thalidomide ,Female ,business ,medicine.drug - Published
- 2013
35. Primary plasma cell leukemia in the era of new drugs: has something changed?
- Author
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Antonino Neri, Fortunato Morabito, Paola Omedè, Pellegrino Musto, Francesco Di Raimondo, Patrizia Tosi, Sara Bringhen, Maria Teresa Petrucci, Tommaso Caravita, Giovanni Battista Bochicchio, Fiorella D'Auria, Antonio Palumbo, Massimo Offidani, Luca Baldini, Livio Pagano, Mario Boccadoro, Michele Cavo, Musto P, Pagano L, Petrucci MT, Morabito F, Caravita T, Di Raimondo F, Baldini L, Tosi P, Bringhen S, Offidani M, Omede' P, Neri A, D'Auria F, Bochicchio GB, Cavo M, Boccadoro M, and Palumbo A
- Subjects
Oncology ,medicine.medical_specialty ,plasmacell leukemia ,Myeloma ,Antineoplastic Agents ,Disease ,Leukemia, Plasma Cell ,Bortezomib ,Autologous stem-cell transplantation ,Internal medicine ,Humans ,Medicine ,Lenalidomide ,Multiple myeloma ,Plasma cell leukemia ,Response rate (survey) ,STEM CELL TRANSPLANTATION ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Thalidomide ,Settore MED/15 - MALATTIE DEL SANGUE ,Immunology ,business ,medicine.drug - Abstract
Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. This disease is associated with a very poor prognosis, and unfortunately it has not significantly improved during the last three decades. Autologous stem cell transplantation is generally recommended in eligible patients, but survival in transplanted PPCL patients is significantly lower than that of multiple myeloma. Recent preliminary data indicate that new drugs, in particular lenalidomide and bortezomib, could significantly improve the clinical outcome of PPCL, increasing response rate and duration, as well as survival. In this review we report an updated literature analysis about the current therapeutic scenario of PPCL, with a particular focus on the use of novel agents.
- Published
- 2012
36. miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1
- Author
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Antonino Neri, Marzia Leotta, Fortunato Morabito, Kenneth C. Anderson, Valter Agosti, Pierosandro Tagliaferri, Gabriella Misso, Anna Maria Gullà, Nikhil C. Munshi, Michele Caraglia, M T Di Martino, Marco Rossi, Maria Rita Pitari, Emanuela Leone, Francesco Conforti, Marta Lionetti, Nicola Amodio, Umberto Foresta, Manlio Ferrarini, Mariateresa Fulciniti, Pierfrancesco Tassone, Amodio, N, Di Martino, Mt, Foresta, U, Leone, E, Lionetti, M, Leotta, M, Gullà, Am, Pitari, Mr, Conforti, F, Rossi, M, Agosti, V, Fulciniti, M, Misso, Gabriella, Morabito, F, Ferrarini, M, Neri, A, Caraglia, Michele, Munshi, Nc, Anderson, Kc, Tagliaferri, P, and Tassone, P.
- Subjects
Male ,Cancer Research ,Sp1 Transcription Factor ,Immunology ,Down-Regulation ,Apoptosis ,Mice, SCID ,Biology ,Sp1 ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,plasma cell leukemia ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Transcription factor ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Feedback, Physiological ,Plasma cell leukemia ,Regulation of gene expression ,0303 health sciences ,Sp1 transcription factor ,microRNA ,Bortezomib ,miR-29b ,bortezomib ,Cell Biology ,medicine.disease ,Boronic Acids ,Molecular biology ,Gene Expression Regulation, Neoplastic ,multiple myeloma ,MicroRNAs ,Proteasome ,Pyrazines ,030220 oncology & carcinogenesis ,miRNAs ,Proteasome inhibitor ,Cancer research ,Original Article ,medicine.drug - Abstract
MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells.
- Published
- 2012
37. The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia
- Author
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Fortunato Morabito, Anna Grazia Recchia, Antonio Pinto, Rosaria De Filippi, Katja Zirlik, Claudio Tripodo, Manlio Ferrarini, Giovanni Del Poeta, Barbara Amoroso, Vincenzo Gigliotti, Emanuela Morelli, Massimo Gentile, Ernesto Vigna, Luca Laurenti, Rosa Calemma, Stefano Molica, Giovanna Cutrona, Antonino Neri, Morabito, F, DE FILIPPI, Rosaria, Laurenti, L, Zirlik, K, Recchia, Ag, Gentile, M, Morelli, E, Vigna, E, Gigliotti, V, Calemma, R, Amoroso, B, Neri, A, Cutrona, G, Ferrarini, M, Molica, S, Del Poeta, G, Tripodo, C, Pinto, A., De Filippi, R, Recchia, AG, and Cutrona
- Subjects
Male ,Chronic lymphocytic leukemia ,MICROENVIRONMENT ,PROGRESSION ,CD38 ,GUIDELINES ,Biochemistry ,Cohort Studies ,Bone Marrow ,LYMPHOMA ,Medicine ,Aged, 80 and over ,Hematology ,Middle Aged ,Prognosis ,Leukemia ,B-CELLS ,Monoclonal ,Disease Progression ,Biological Markers ,Female ,IGHV@ ,Algorithms ,Adult ,medicine.medical_specialty ,DISORDERS ,CLINICAL-SIGNIFICANCE ,CD38 EXPRESSION ,CLL ,DIAGNOSIS ,Immunology ,Immunoglobulin light chain ,Immunoglobulin kappa-Chains ,Immunoglobulin lambda-Chains ,Humans ,Survival analysis ,Aged ,business.industry ,Cytogenetics ,Cell Biology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Cancer research ,Immunoglobulin Light Chains ,Lymph Nodes ,business ,Settore MED/15 - Malattie del Sangue ,Biomarkers ,Follow-Up Studies - Abstract
Identification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated with cytogenetic risk, exceeds the threshold of 60.6 mg/mL. Patients with sFLC(κ + λ) above cut-off displayed a poorer TFS outcome, irrespective of sFLC(κ/λ). Only ZAP-70, cytogenetics, stage, and TFS remained associated with sFLC(κ + λ) in a multivariate model. By assigning 1 point each for these variables, the 3-year probability of TFS was 94.8%, 84.5%, 61.6%, and 21.1% for patients scoring 0, 1, 2, and 3 + 4, respectively (P < .0001). These data, and the demonstration that monoclonal and polyclonal B cells concur to FLC synthesis in tumor tissues, suggest that sFLC(κ/λ) and sFLC(κ + λ) mirror distinct biologic processes in CLL. sFLC(κ + λ) assessment represents a sensitive and cost-effective tool for identifying CLL patients requiring early treatment.
- Published
- 2011
38. Cytological and histological detection of amyloid deposits in bone marrow of patients affected by multiple myeloma
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Eugenio Piro, Pellegrino Musto, Fabrizio Pane, Rosanna Ciancia, Giulia Vita, Laura Virginia Sosa Fernandez, Lucio Catalano, Immacolata Cozzolino, Giuseppe Ciancia, Fiorella D'Auria, Fortunato Morabito, Pio Zeppa, Maria Rita Costanza Ponti, Guido Pettinato, Fara Petruzziello, Mariarosaria Cervasio, Petruzziello, F, Zeppa, P, Ciancia, G, Cozzolino, I, Fernandez, L, Cervasio, M, Musto, P, D'Auria, F, Vita, G, Morabito, F, Piro, E, Ponti, Mr, Pettinato, G, Ciancia, R, Pane, Fabrizio, and Catalano, Lucio
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Amyloid ,Plaque, Amyloid ,Immunoglobulin Light-chain Amyloidosis ,Bone Marrow ,Biopsy ,Humans ,Medicine ,Iliac spine ,Multiple myeloma ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Biopsy, Needle ,Hematology ,Middle Aged ,medicine.disease ,Systemic amyloidosis ,medicine.anatomical_structure ,Oncology ,Female ,Bone marrow ,Multiple Myeloma ,business ,Core biopsy - Abstract
We recently published a study aiming to verify the frequency of amyloid deposits in the bone marrow of patients with multiple myeloma (MM) who did not present any signs or symptoms of systemic amyloidosis, applying the Congo red technique on bone marrow smears obtained by aspiration from the posterior iliac spine. The results suggested that nearly 40% of patients affected by MM may have amyloid deposits in their bone marrow. Subsequently, this finding has not been confirmed by another study performed with histological specimens of bone marrow in a similar clinical setting. To explain this discrepancy, we performed a comparative study on the bone marrows of 36 patients affected by MM, evaluated by both cytological and histological techniques. The results of this study confirm the high frequency of amyloid deposits in the bone marrow of patients affected by MM when the analysis is made on cytological smears, and indicate that the presence of amyloid on marrow smears is confirmed by core biopsies simultaneously performed in only 25% of cases. Should further studies confirm our findings, cytological assessment could be considered a sensitive technique to detect bone marrow amyloid deposits.
- Published
- 2011
39. Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches
- Author
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Mario Boccadoro, Orhan Sezer, Martin Kropff, Donald Bunjes, Andrew Spencer, Martina Kleber, Rom Hajek, Stefan Knop, Fortunato Morabito, Michele Cavo, Benedetto Bruno, Francesca Patriarca, Martin Gramatzki, Ralph Wäsch, Josefina Udi, Christian Straka, Monika Engelhardt, Hermann Einsele, Aaron Polliack, Antonino Neri, Antonio Palumbo, Engelhardt M, Kleber M, Udi J, Wäsch R, Spencer A, Patriarca F, Knop S, Bruno B, Gramatzki M, Morabito F, Kropff M, Neri A, Sezer O, Hajek R, Bunjes D, Boccadoro M, Straka C, Cavo M, Polliack A, Einsele H, and Palumbo A.
- Subjects
Cancer Research ,medicine.medical_specialty ,Consensus ,medicine.medical_treatment ,Art therapy ,Antineoplastic Agents ,Quality of life ,medicine ,Humans ,Intensive care medicine ,Multiple myeloma ,Lenalidomide ,Chemotherapy ,Bortezomib ,business.industry ,Remission Induction ,Hematology ,medicine.disease ,Surgery ,Thalidomide ,medicine.anatomical_structure ,Oncology ,Practice Guidelines as Topic ,Bone marrow ,Multiple Myeloma ,business ,Stem Cell Transplantation ,medicine.drug - Abstract
Treatment for multiple myeloma (MM) has changed beyond recognition over the past two decades. During the early 1980s, MM inevitably resulted in a slow progressive decline in quality of life until death after about 2 years, while today patients can expect a 50% chance of achieving a complete remission, median survival of 5 years, and a 20% chance of surviving longer than 10 years. An international expert opinion meeting (including members of the GIMEMA and DSMM study groups) was held in 2009. One of the outcomes of the meeting was the development of a consensus statement outlining contemporary optimal clinical practice for the treatment of MM. The international panel recommended that the state of the art therapy for MM should comprise: (a) evidence-based supportive care, (b) effective and well-tolerated chemotherapeutic regimens, (c) autologous hematopoietic stem cell transplant (ASCT) for patients suitable for intensive conditioning therapy, and (d) evidence-based incorporation of novel anti-MM agents. Maintenance strategies have also become increasingly important for the prolongation of remission after front-line therapies. In addition, improved understanding of the biology of MM has led to the development of novel biological therapeutic agents such as thalidomide, lenalidomide, bortezomib, and others. These agents specifically target intracellular mechanisms and interactions, such as those within the bone marrow microenvironment, and have been integrated into MM treatment. This report reviews recent clinical advances in the treatment strategies available for MM and provides an overview of the state of the art management of patients with MM.
- Published
- 2010
40. Safety and efficacy of bortezomib-based regimens for multiple myeloma patients with renal impairment: a retrospective study of Italian Myeloma Network GIMEMA
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Fortunato Morabito, Lucio Catalano, Eugenio Piro, Sara Galimberti, Donato Mannina, Antonio Francesco Casulli, Sara Bringhen, Luca Baldini, Michele Cavo, Mario Boccadoro, Massimo Offidani, Patrizia Tosi, Salvatore Palmieri, Vincenzo Callea, Giuseppe Mele, Graziella Pinotti, Francesco Di Raimondo, Massimo Gentile, Antonio Palumbo, Pellegrino Musto, Maria Teresa Petrucci, Stefania Ciolli, Morabito F, Gentile M, Ciolli S, Petrucci MT, Galimberti S, Mele G, Casulli AF, Mannina D, Piro E, Pinotti G, Palmieri S, Catalano L, Callea V, Offidani M, Musto P, Bringhen S, Baldini L, Tosi P, Di Raimondo F, Boccadoro M, Palumbo A, and Cavo M.
- Subjects
Male ,Gastrointestinal Diseases ,medicine.medical_treatment ,Gastroenterology ,Dexamethasone ,Bortezomib ,Antineoplastic Combined Chemotherapy Protocols ,Multicenter Studies as Topic ,Melphalan ,Multiple myeloma ,Aged, 80 and over ,Clinical Trials as Topic ,Peripheral Nervous System Diseases ,Hematology ,General Medicine ,Middle Aged ,Boronic Acids ,Neoplasm Proteins ,Thalidomide ,Italy ,Cardiovascular Diseases ,Pyrazines ,Female ,Kidney Diseases ,Multiple Myeloma ,Proteasome Inhibitors ,Glomerular Filtration Rate ,medicine.drug ,medicine.medical_specialty ,Renal function ,Internal medicine ,medicine ,Humans ,Protease Inhibitors ,Renal replacement therapy ,Cyclophosphamide ,Dialysis ,Survival analysis ,Aged ,Retrospective Studies ,business.industry ,Retrospective cohort study ,medicine.disease ,Hematologic Diseases ,Survival Analysis ,Surgery ,Discontinuation ,Doxorubicin ,business ,Follow-Up Studies - Abstract
Renal impairment (RI) is a severe complication throughout the course of multiple myeloma (MM). Bortezomib has been shown to be highly active in MM patients with RI. We designed this retrospective analysis to investigate the safety and efficacy of bortezomib-based therapy in 117 MM patients with RI, 14 cases required dialysis. A total of 603 cycles of bortezomib were administered (median number, five cycles/patient). Ten patients required early discontinuation of bortezomib because of WHO grade IV toxicity. The rate of bortezomib discontinuation in cases with severe, moderate and mild RI was 11%, 5% and 0%, respectively (P = NS). Overall, 91 episodes of WHO grade III/IV toxicity were observed. At least a partial response was documented in 83/113 evaluable patients (73%), including complete response (19%) and near complete response (8%). The overall response rate was similar across RI subgroups. Reversal of RI was documented in 41% of patients after a median of 2.3 months (range 0.4-7.9). In three of 14 patients on dialysis, renal replacement therapy was discontinued after 1, 1 and 4 months. The 2-yr estimate of response duration and overall survival was 70% and 51%, respectively. In conclusion, bortezomib-based regimens are safe and effective and should be considered as appropriate treatment options for MM patients with any degree of RI.
- Published
- 2010
41. First-line treatment of multiple myeloma in elderly patients: the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) multiple myeloma working party perspective
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Pellegrino Musto, Fiorella D'Auria, Giuseppe Pietrantuono, Luca Baldini, Sara Bringhen, Tommaso Caravita, Francesco Di Raimondo, Fortunato Morabito, Massimo Offidani, Maria Petrucci, Patrizia Tosi, Francesca Gay, Michele Cavo, Mario Boccadoro, Antonio Palumbo, Musto P, D'Auria F, Pietrantuono G, Baldini L, Bringhen S, Caravita T, Di Raimondo F, Morabito F, Offidani M, Petrucci MT, Tosi P, Gay F, Cavo M, Boccadoro M, and Palumbo A.
- Subjects
Oncology ,Melphalan ,Autologous transplantation ,medicine.medical_specialty ,Transplantation Conditioning ,Clinical Biochemistry ,Myeloma ,Reduced-intensity allogeneic transplantation ,Dexamethasone ,Bortezomib ,Elderly ,Internal medicine ,Drug Discovery ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cyclophosphamide ,Lenalidomide ,Multiple myeloma ,Aged ,Pharmacology ,Performance status ,business.industry ,medicine.disease ,Combined Modality Therapy ,Thalidomide ,Surgery ,Transplantation ,Survival Rate ,Treatment Outcome ,Doxorubicin ,Bendamustine ,Quality of Life ,Molecular Medicine ,business ,Multiple Myeloma ,medicine.drug ,Stem Cell Transplantation - Abstract
Multiple myeloma (MM) is a neoplastic disorder affecting elderly people. The treatment for all patients with MM was, for about 40 years, based on the combination of melphalan plus prednisone, with a very low rate of complete remissions and a survival that remained unacceptably low (about 36 months). Diverse factors, including comorbidity, performance status, decreased physiologic reserve, and potential undertreatment, contribute to these poor outcomes. Recently, however, the reduced treatment-related morbidity and mortality associated with autologous stem-cell transplantation and the availability of effective new drugs with acceptable toxicity, such as thalidomide, lenalidomide and bortezomib, have greatly modified the traditional treatment paradigms in older patients with MM, challenging, in some cases, the definition of elderly and rapidly transforming the traditional palliative treatments to a new global therapeutic strategy, with the final objective of significantly improving the quality and the duration of life for elderly people with this disease. In this review, we report updated data for the front-line treatment of MM in the elderly population, examining the role of new drugs combined with melphalan or their incorporation within more complex combinations, including other so-called conventional drugs such as (pegylated)-doxorubicin, cyclophosphamide, and dexamethasone. We also assess the role of autologous and allogeneic stem-cell transplantation with adjusted conditioning regimens in selected elderly patients. © 2009 Bentham Science Publishers Ltd.
- Published
- 2009
42. Considerations in the treatment of multiple myeloma: a consensus statement from Italian experts
- Author
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Paolo Corradini, Gianpietro Semenzato, Massimo Offidani, Rita Rizzi, Felicetto Ferrara, Francesco Di Raimondo, Luca Baldini, Antonio Palumbo, Fortunato Morabito, Sara Bringhen, Mario Petrini, Tommaso Caravita, Angelo Vacca, Antonietta Falcone, Francesca Patriarca, Patrizia Tosi, Maria Teresa Petrucci, Alessandro Corso, Pellegrino Musto, Mario Boccadoro, Michele Cavo, Patriarca F, Petrucci MT, Bringhen S, Baldini L, Caravita T, Corradini P, Corso A, Di Raimondo F, Falcone A, Ferrara F, Morabito F, Musto P, Offidani M, Petrini M, Rizzi R, Semenzato G, Tosi P, Vacca A, Cavo M, Boccadoro M, and Palumbo A.
- Subjects
Melphalan ,Oncology ,Adult ,medicine.medical_specialty ,Adolescent ,Myeloma ,Autologous stem-cell transplantation ,Recurrence ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Multiple myeloma ,Lenalidomide ,Aged ,TRANSPLANTATION ,Bortezomib ,business.industry ,Hematology ,General Medicine ,CHEMOTHERAPY ,Middle Aged ,medicine.disease ,Thalidomide ,Transplantation ,CLINICAL PRACTICE GUIDELINES ,Regimen ,Italy ,business ,Multiple Myeloma ,medicine.drug - Abstract
PURPOSE AND BASIC PROCEDURE OF THE STUDY: The availability of new targeted therapies has revolutionised the treatment of multiple myeloma (MM), for both the newly diagnosed and the relapsed and refractory settings. A panel of Italian experts provided guidelines for optimal clinical practice in the treatment of MM. MAIN FINDINGS AND CONCLUSIONS: The panel recommended that treatment should only be initiated in symptomatic patients. Autologous stem cell transplantation (ASCT) with melphalan is the treatment of choice in patients younger than 65 yr, and induction therapy including new drugs seems the most suitable preparatory regimen before ASCT. In patients who fail to achieve at least a very good partial response (VGPR) after transplant, a consolidation with a second transplant is of clinical benefit. Also, there is evidence that maintenance with thalidomide after ASCT in young patients failing to reach at least VGPR could prolong survival. In elderly patients, the combination of an alkylating drug with a novel agent should be considered as standard approach. Relapsed MM should be retreated after the reappearance of symptoms and signs of organ and tissue damage. Salvage regimens should include corticosteroids plus bortezomib, thalidomide or lenalidomide.
- Published
- 2008
43. Peg-filgrastim versus filgrastim after autologous stem cell tranplantation: case-control study in patients with multiple myeloma and review of the literature
- Author
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Pellegrino Musto, Giuseppe Messina, Fortunato Morabito, Potito Rosario Scalzulli, Grazia Sanpaolo, Maria Rosa Valvano, Fiorella D'Auria, Antonietta Falcone, Roberto Guariglia, Giuseppe Pietrantuono, Elisabetta Terruzzi, Fausto Rossini, Oreste Villani, Enrico Pogliani, Pasquale Iacopino, Musto, P, Scalzulli, P, Terruzzi, E, Rossini, F, Iacopino, P, Messina, G, Guariglia, R, Pietrantuono, G, Villani, O, D'Auria, F, Falcone, A, Sanpaolo, G, Valvano, M, Pogliani, E, and Morabito, F
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Filgrastim ,Neutropenia ,Polyethylene Glycol ,Polyethylene Glycols ,Autologous stem-cell transplantation ,MED/15 - MALATTIE DEL SANGUE ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Autologous transplantation ,Multiple myeloma ,business.industry ,Hematology ,medicine.disease ,Recombinant Proteins ,Surgery ,Granulocyte colony-stimulating factor ,Treatment Outcome ,Tolerability ,Case-Control Studies ,business ,Multiple Myeloma ,Febrile neutropenia ,medicine.drug ,Stem Cell Transplantation ,Human - Abstract
We investigated the effects of a single s.c. injection of peg-filgrastim in 32 patients with multiple myeloma who underwent autologous stem cell transplantation (AuSCT) as first line treatment. For comparison, 32 myeloma patients with similar characteristics and receiving standard daily administration of filgrastim were matched. Overall, there were no statistically significant differences between peg-filgrastim and filgrastim in terms of tolerability, marrow recovery, severity of neutropenia, incidence and duration of febrile neutropenia, documented infections and transfusions. However, some favourable trends or effects in favour of peg-filgrastim were observed. This was confirmed by a review of the published papers about this topic.
- Published
- 2007
44. PDGFRalpha/FIP1L1-positive chronic eosinophilic leukemia presenting with retro-orbital localization: efficacy of imatinib treatment
- Author
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Fortunato Morabito, Emanuela Ottaviani, Eugenio Lucia, Carlo Gentile, Michela Rondoni, Maria Grazia Bisconte, Giovanni Martinelli, Ernesto Vigna, Carla Mazzone, Antonio Armentano, Massimo Gentile, Vigna E, Lucia E, Gentile M, Mazzone C, Bisconte MG, Gentile C, Armentano A, Ottaviani E, Rondoni M, Martinelli G, and Morabito F.
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Receptor, Platelet-Derived Growth Factor alpha ,Oncogene Proteins, Fusion ,medicine.drug_class ,Antineoplastic Agents ,Toxicology ,IMATINIB ,Gastroenterology ,Tyrosine-kinase inhibitor ,Piperazines ,Internal medicine ,Hypereosinophilic Syndrome ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,mRNA Cleavage and Polyadenylation Factors ,Chronic eosinophilic leukemia ,ABL ,Hypereosinophilic syndrome ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Imatinib ,Hypoesthesia ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Imatinib mesylate ,Pyrimidines ,Oncology ,CHRONIC EOSINOPHILIC LEUKEMIA ,Benzamides ,Cancer research ,Imatinib Mesylate ,Orbital Neoplasms ,medicine.symptom ,business ,Tomography, X-Ray Computed ,Tyrosine kinase ,medicine.drug - Abstract
The fusion protein between the platelet-derived growth factor receptor alpha (PDGFRalpha, P) gene and the Fip1-like1 (FIP1L1, F) may be identified in 14 to 60% of HES and it indicates a clonal hypereosinophilic syndrome called F/P-positive CEL. We herein report a case of F/P-positive CEL with retro-orbital localization, who was successfully treated with imatinib. CASE REPORT: A 53-year-old male presented an absolute eosinophil count of 25,000/mm(3), anemia (Hb 10.2 g/dl) and a moderate increase in the platelet count (571,000/mm(3)). A clinical examination revealed left exophthalm, associated with diffuse hypoesthesia and diplopia. A CT scan of orbits showed a lesion located in the lachrymal fossa of the left orbit with intra- and extra-conical extension. Molecular analysis excluded the presence of bcr/abl transcript while a F/P fusion tyrosine kinase signal was documented. Imatinib mesylate (IM) was started and, after 7 days of treatment eosinophil count significantly declined along with a dramatic reduction of the left exophthalm. IM dosage was increased up to 300 mg/day. The drug was well tolerated with an initial modest haematological toxicity. The left exophthalm, as well as hypoesthesia and diplopia, disappeared after IM therapy. MRI showed a clear reduction of the intra- and extra-conical growth process. BM molecular signal of the F/P fusion gene resulted undetectable after 4 weeks of treatment. CONCLUSION: In our case, the diagnosis of FIPIL1-PDGFRA-positive CEL and IM therapy has allowed the patient to experience an excellent clinical therapeutic result, avoiding surgical treatment of the retro-orbital mass.
- Published
- 2007
45. CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy
- Author
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P Boccuni, Bruno Martino, Cesare Guglielmi, Fabrizio Pane, Mario Annunziata, Rosa Di Noto, Francesco Nobile, Giorgina Specchia, Mariacarla De Simone, Ettore Mariano Schiavone, Fortunato Morabito, Vincenzo Liso, Felicetto Ferrara, Francesco Lo Coco, Luigi Del Vecchio, Ferrara, F., Morabito, F., Martino, B., Specchia, G., Liso, V., Nobile, F., Boccuni, P., DI NOTO, Rosa, Pane, Fabrizio, Annunziata, M., Schiavone, E. M., De Simone, M., Guglielmi, C., DEL VECCHIO, Luigi, and Lo Coco, F.
- Subjects
Acute promyelocytic leukemia ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Tretinoin ,Acute ,Leukemia, Promyelocytic, Acute ,Multicenter trial ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Coagulopathy ,medicine ,Idarubicin ,Humans ,Antigens ,Preschool ,Child ,Aged ,Promyelocytic ,Chemotherapy ,Leukemia ,business.industry ,Myeloid leukemia ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,CD56 Antigen ,Child, Preschool ,Immunology ,Multivariate Analysis ,Female ,CD56 ,business ,Settore MED/15 - Malattie del Sangue ,medicine.drug ,Antigens, CD56 - Abstract
PURPOSE: Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy. PATIENTS AND METHODS: Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis. RESULTS: Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56+. No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56+ and CD56− populations. Conversely, compared with patients who were CD56−, patients with CD56+ APL had shorter CR duration (P = .04) and overall survival (P = .002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 × 109 cells/L retained statistical significance in overall survival (P = .04 and P = .02, respectively). CONCLUSION: The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.
- Published
- 2000
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