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311 results on '"Gugliotta, G"'

1. Detection of the Cherenkov light diffused by Sea Water with the ULTRA Experiment

Author

Agnetta, G., Assis, P., Biondo, B., Brogueira, P., Cappa, A., Catalano, O., Chauvin, J., Staiti, G. D'Ali', Dattoli, M., Espirito-Santo, M. C., Fava, L., Galeotti, P., Giarrusso, S., Gugliotta, G., La Rosa, G., Lebrun, D., Maccarone, M. C., Mangano, A., Melo, L., Moreggia, S., Pimenta, M., Russo, F., Saavedra, O., Segreto, A., Silva, J. C., Stassi, P., Tome', B., Vallania, P., and Vigorito, C.

Subjects
Astrophysics
Abstract

The study of Ultra High Energy Cosmic Rays represents one of the most challenging topic in the Cosmic Rays and in the Astroparticle Physics fields. The interaction of primary particles with atmospheric nuclei produces a huge Extensive Air Shower together with isotropic emission of UV fluorescence light and highly directional Cherenkov photons, that are reflected/diffused isotropically by the impact on the Earth's surface or on high optical depth clouds. For space-based observations, detecting the reflected Cherenkov signal in a delayed coincidence with the fluorescence light improves the accuracy of the shower reconstruction in space and in particular the measurement of the shower maximum, giving a strong signature for discriminating hadrons and neutrinos, and helping to estimate the primary chemical composition. Since the Earth's surface is mostly covered by water, the ULTRA (UV Light Transmission and Reflection in the Atmosphere)experiment has been designed to provide the diffusing properties of sea water, overcoming the lack of information in this specific field. A small EAS array, made up of 5 particle detectors, and an UV optical device, have been coupled to detect in coincidence both electromagnetic and UV components. The detector was in operation from May to December, 2005, in a small private harbor in Capo Granitola (Italy); the results of these measurements in terms of diffusion coefficient and threshold energy are presented here., Comment: 4 pages, 3 figures, PDF format, Proceedings of 30th ICRC, International Cosmic Ray Conference 2007, Merida, Yucatan, Mexico, 3-11 July 2007

Published
2007

2. Results from the ULTRA experiment in the framework of the EUSO project

Author

Agnetta, G., Assis, P., Biondo, B., Brogueira, P., Cappa, A., Catalano, O., Chauvin, J., Staiti, G. D'Ali, Dattoli, M., Espirito-Santo, M. C., Fava, L., Galeotti, P., Giarrusso, S., Gugliotta, G., La Rosa, G., Lebrun, D., Maccarone, M. C., Mangano, A., Melo, L., Moreggia, S., Pimenta, M., Russo, F., Saavedra, O., Scarsi, P., Silva, J. C., Stassi, P., Tomè, B., Vallania, P., Vigorito, C., and Collaboration, the EUSO

Subjects
Astrophysics
Abstract

The detection of Cerenkov light from EAS in a delayed coincidence with fluorescence light gives a strong signature to discriminate protons and neutrinos in cosmic rays. For this purpose, the ULTRA experiment has been designed with 2 detectors: a small EAS array (ETscope) and an UV optical device including wide field (Belenos) and narrow field (UVscope) Cerenkov light detectors. The array measures the shower size and the arrival direction of the incoming EAS, while the UV devices, pointing both to zenith and nadir, are used to determine the amount of direct and diffused coincident Cerenkov light. This information, provided for different diffusing surfaces, will be used to verify the possibility of detecting from Space the Cerenkov light produced by UHECRs with the EUSO experiment, on board the ISS.

Published
2006

3. GAW (Gamma Air Watch): a novel imaging Cherenkov telescope

Author

Cusumano, G., Agnetta, G., Biondo, B., Catalano, O., Giarrusso, S., Gugliotta, G., La Fata, L., Maccarone, M. C., Mangano, A., Mineo, T., Russo, F., and Sacco, B.

Subjects
Astrophysics
Abstract

GAW (Gamma Air Watch) is a new imaging Cherenkov telescope designed for observation of very high-energy gamma-ray sources. GAW will be equipped with a 3 meter diameter Fresnel lens as light collector and with an array of 300 multi-anode photomultipliers at the focal plane. The pixel size will be 4 arcmin wide for a total field of view of 10.5 degrees. Whith respect to the planned imaging Cherenkov telescopes (CANGAROO III, HESS, MAGIC, VERITAS) GAW follows a different approach for what concerns both the optical system and the detection working mode: the Cherenkov light collector is a single acrylic flat Fresnel lens (instead of mirrors) that allows to achieve wide field of view; the photomultipliers operate in single photoelectron counting mode (instead of charge integration). The single photoelectron counting mode allows to reach a low energy threshold of ~200 GeV, in spite of the relatively small dimension of the GAW optic system., Comment: 5 pages, 3figures, to be published in the proceedings of Frascati Workshop 2001 Vulcano, May 21-26, 2001

Published
2001

4. Efficacy and safety of nilotinib as frontline treatment in elderly (> 65 years) chronic myeloid leukemia patients outside clinical trials

Author

Luciano, L., Latagliata, R., Gugliotta, G., Annunziata, M., Tiribelli, M., Martino, B., Sica, A., Esposito, M. R., Bocchia, M., Galimberti, S., Sora', Federica, Albano, F., Palmieri, R., Pregno, P., Dragani, M., Iovine, M., Sica, Simona, Iurlo, A., Castagnetti, F., Rosti, G., Breccia, M., Sora' F. (ORCID:0000-0002-9607-5298), Sica S. (ORCID:0000-0003-2426-3465), Luciano, L., Latagliata, R., Gugliotta, G., Annunziata, M., Tiribelli, M., Martino, B., Sica, A., Esposito, M. R., Bocchia, M., Galimberti, S., Sora', Federica, Albano, F., Palmieri, R., Pregno, P., Dragani, M., Iovine, M., Sica, Simona, Iurlo, A., Castagnetti, F., Rosti, G., Breccia, M., Sora' F. (ORCID:0000-0002-9607-5298), and Sica S. (ORCID:0000-0003-2426-3465)

Abstract

Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65–84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response.

Published
2023

6. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

Salvi, F., Pini, M., Leoni, P., Rupoli, S., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Albano, F., Russo Rossi, A., Rambaldi, A., Intermesoli, T., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, M.T., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Malagola, M., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., Storti, S., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Impera, S., Molica, S., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cavazzini, F., Bosi, A., Santini, V., Capalbo, S.F., Spinosa, G., Pierri, I., Bergamaschi, M., Carella, A.M., Bacigalupo, A., De Blasio, A., Ciccone, F., Di Renzo, N., Musolino, C., Russo, S., Cortelezzi, A., Morra, E., Pungolino, E.M., Luppi, M., Marasca, R., Pogliani, E.M., Gambacorti-Passerini, C., Luciano, L., Ferrara, F., Annunziata, M., Latte, G., Noli, D., Rege-Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Aversa, F., Crugnola, M., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidori, A., Fioritoni, G., Di Lorenzo, R., Vallisa, D., Trabacchi, E., Petrini, M., Galimberti, S., Pizzuti, M., Zaccaria, A., Salvucci, M., Ronco, F., Ielo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Musto, P., De Stefano, V., Sica, S., Latagliata, R., De Fabritiis, P., Trawiska, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Petti, M.C., Pisani, F., Tafuri, A., Montefusco, E., Iuliano, F., Dore, F., Pardini, S., Bocchia, M., Defina, M., Liberati, A.M., Luzzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Gherlinzoni, F., Calistri, E., Fanin, R., Pizzolo, G., Meneghini, V., Rodighiero, F., D'Emilio, A., Castagnetti, F., Gugliotta, G., Baccarani, M., Breccia, M., Specchia, G., Levato, L., Abruzzese, E., Rossi, G., Iurlo, A., Martino, B., Pregno, P., Stagno, F., Cuneo, A., Bonifacio, M., Gobbi, M., Russo, D., Gozzini, A., Tiribelli, M., de Vivo, A., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., and Rosti, G.

Published
2015
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7. P698: BOSUTINIB DOSE OPTIMIZATION IN THE SECOND-LINE TREATMENT OF ELDERLY CML PATIENTS: EXTENDED 3-YEAR FOLLOW-UP AND FINAL RESULTS OF THE BEST STUDY

Author

Castagnetti, F., primary, Bocchia, M., additional, Abruzzese, E., additional, Capodanno, I., additional, Bonifacio, M., additional, Rege Cambrin, G., additional, Crugnola, M., additional, Binotto, G., additional, Elena, C., additional, Lucchesi, A., additional, Bergamaschi, M., additional, Albano, F., additional, Luciano, L., additional, Sorà, F., additional, Lunghi, F., additional, Stagno, F., additional, Cerrano, M., additional, Iurlo, A., additional, Scortechini, A. R., additional, Leonetti Crescenzi, S., additional, Spadano, R., additional, Trabacchi, E., additional, Lunghi, M., additional, Spinosa, G., additional, Ferrero, D., additional, Rapezzi, D., additional, Ladetto, M., additional, Nocilli, L., additional, Gugliotta, G., additional, Iezza, M., additional, Cavo, M., additional, Saglio, G., additional, Pane, F., additional, and Rosti, G., additional

Published
2022
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8. S152: SETD2/H3K36ME3 DEFICIENCY SUSTAINS GENOMIC INSTABILITY AND ENHANCES CLONOGENIC POTENTIAL OF CHRONIC MYELOID LEUKEMIA (CML) PROGENITORS

Author

Mancini, M., primary, De Santis, S., additional, Monaldi, C., additional, Bruno, S., additional, Castagnetti, F., additional, Gugliotta, G., additional, Iurlo, A., additional, Cerrano, M., additional, Galimberti, S., additional, Balducci, S., additional, Stagno, F., additional, Rosti, G., additional, Cavo, M., additional, and Soverini, S., additional

Published
2022
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9. COVID-19 infection in chronic myeloid leukemia after one year of the pandemic in Italy Campus CML report

Author

Breccia, M, Abruzzese, E, Accurso, V, Attolico, I, Barulli, S, Bergamaschi, M, Binotto, G, Bocchia, M, Bonifacio, M, Caocci, G, Capodanno, I, Castagnetti, F, Cavazzini, F, Crisà, E, Crugnola, M, De Candia, M, Elena, C, Fava, C, Galimberti, S, Gozzini, A, Gugliotta, G, Intermesoli, T, Iurlo, A, La Barba, G, Latagliata, R, Crescenzi, Sl, Levato, L, Loglisci, G, Lucchesi, A, Luciano, L, Lunghi, F, Luzi, D, Malato, A, Miggiano, Mc, Pizzuti, M, Pregno, P, Rapezzi, D, Rege-Cambrin, G, Rosti, G, Russo, S, Sancetta, R, Scortechini, Ar, Sora', Federica, Sportoletti, P, Stagno, F, Tafuri, A, Tiribelli, M, Foà, R, Saglio, G, Sora, Federica (ORCID:0000-0002-9607-5298), Breccia, M, Abruzzese, E, Accurso, V, Attolico, I, Barulli, S, Bergamaschi, M, Binotto, G, Bocchia, M, Bonifacio, M, Caocci, G, Capodanno, I, Castagnetti, F, Cavazzini, F, Crisà, E, Crugnola, M, De Candia, M, Elena, C, Fava, C, Galimberti, S, Gozzini, A, Gugliotta, G, Intermesoli, T, Iurlo, A, La Barba, G, Latagliata, R, Crescenzi, Sl, Levato, L, Loglisci, G, Lucchesi, A, Luciano, L, Lunghi, F, Luzi, D, Malato, A, Miggiano, Mc, Pizzuti, M, Pregno, P, Rapezzi, D, Rege-Cambrin, G, Rosti, G, Russo, S, Sancetta, R, Scortechini, Ar, Sora', Federica, Sportoletti, P, Stagno, F, Tafuri, A, Tiribelli, M, Foà, R, Saglio, G, and Sora, Federica (ORCID:0000-0002-9607-5298)

Abstract

Limited information is available on the impact of the COVID-19 pandemic on the management of chronic myeloid leukaemia (CML). The Campus CML network collected retrospective information on 8 665 CML patients followed at 46 centres throughout Italy during the pandemic between February 2020 and January 2021. Within this cohort, we recorded 217 SARS-CoV-2-positive patients (2·5%). Most patients (57%) were diagnosed as having SARS-CoV-2 infection during the second peak of the pandemic (September 2020 to January 2021). The majority (35%) was aged between 50 and 65 years with a male prevalence (73%). Fifty-six percent of patients presented concomitant comorbidities. The median time from CML diagnosis to SARS-CoV-2 infection was six years (three months to 18 years). Twenty-one patients (9·6%) required hospitalization without the need of respiratory assistance, 18 (8·2%) were hospitalized for respiratory assistance, 8 (3·6%) were admitted to an intensive care unit, while 170 (78%) were only quarantined. Twenty-three percent of patients discontinued tyrosine kinase inhibitor (TKI) therapy during the infection. Twelve patients died due to COVID-19 with a mortality rate of 5·5% in the positive cohort and of 0·13% in the whole cohort. We could also document sequelae caused by the SARS-CoV-2 infection and an impact of the pandemic on the overall management of CML patients.

Published
2022

11. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

Author

Baccarani, M, Castagnetti, F, Gugliotta, G, Rosti, G, Soverini, S, Albeer, A, Pfirrmann, M, Bekadja, Ma, Entasoltan, B, Nachi, M, Elghandour, A, El Sorady, M, Abdelfattah, R, El Nahass, Y, Samra, M, Azzazi, M, Elsobki, E, Moussa, M, Fahmy, O, Mattar, M, Shehata, Azmy, Se, (Azmy, E, 9 ), Emad), Bolarinwa, (Bolarinwa, Ra, ( 10 ), Rahman A., Eid, (Eid, S, Samir)( 11, ), Khelif, (Khelif, A, Abderrhaim)( 11, ), Hached, (Hached, F, Farhat)( 11, ), Menif, (Menif, S, Samia)( 12, ), Rahman, (Rahman, H, Hafizur)( 13, ), Huang, (Huang, Xj, Xiaojun)(, 14, 15, ), Jiang, (Jiang, Q, Qian)(, 14, (Ye, Yx, Yuanxin)( 16, ), Zhu, (Zhu, Hl, Huanling)( 16, ), Chen, (Chen, Sn, Suning)( 17, ), Varma, (Varma, N, Neelam)( 18, ), Ganesan, (Ganesan, P, Prasanth)( 19, ), Gundeti, (Gundeti, S, Sadashivudu)( 20, ), Malhotra, (Malhotra, H, Hemant)( 21, ), Radhakrishnan, (Radhakrishnan, Vs, ( 22 ), Vivek S., Kumar, (Kumar, L, Lalit)( 23, ), Sharawat, (Sharawat, Sk, Surender Kumar)( 23, ), Seth, (Seth, T, Tulika)( 24, ), Ausekar, (Ausekar, Bv, ( 25 ), B. V., Balasubramanian, (Balasubramanian, P, Poonkuzhali)( 26, ), Poopak, (Poopak, B, Behzad)(, 27, 28, ), Inokuchi, (Inokuchi, K, Koiti)( 29, ), Kim, (Kim, Dw, Dong-Wook)( 30, ), Kindi, Al, S (Al Kindi, Salam)( 31, ), Mirasol, (Mirasol, A, Angelina)( 32, ), Qari, (Qari, M, Mohammed)( 33, ), Goh, (Goh, Yt, Yeow Tee)( 34, ), Shih, (Shih, Ly, Lee-Yung)(, 35, 36, ), Branford, (Branford, S, Susan)(, 37, 38, ), Lion, (Lion, T, Thomas)( 39, ), Valent, (Valent, P, Peter)( 40, ), Burgstaller, (Burgstaller, S, Sonja)( 41, ), Thaler, (Thaler, J, Joseph)( 41, ), Labar, (Labar, B, Boris)( 42, ), Zadro, (Zadro, R, Renata)( 42, ), Mayer, (Mayer, J, Jiri)(, 43, 44, ), Zackova, (Zackova, D, Daniela)(, 43, Faber, (Faber, E, Edgar)( 45, ), Pallisgaard, (Pallisgaard, N, Niels)( 46, ), Xavier-Mahon, (Xavier-Mahon, F, Francois)( 47, ), Lippert, (Lippert, E, Eric)( 48, ), Cayuela, (Cayuela, Jm, Jean Michel)( 49, ), Rea, (Rea, D, Delphine)( 49, ), Millot, (Millot, F, Frederic)( 50, ), Suttorp, (Suttorp, M, Meinolf)( 51, ), Hochhaus, (Hochhaus, A, Andreas)( 52, ), Niederwieser, (Niederwieser, D, Dietger)( 53, ), Saussele, (Saussele, S, Susanne)( 54, ), Haferlach, (Haferlach, T, Torsten)( 55, ), Jeromine, (Jeromine, S, Sabine)( 55, ), Panayiotidis, (Panayiotidis, P, Panayiotis)(, 56, 57, ), Conneally, (Conneally, E, Eibhlin)( 58, ), Langabeer, (Langabeer, S, Steve)( 58, ), Nagler, (Nagler, A, Arnon)(, 59, 60, ), Rupoli, (Rupoli, S, Serena)( 61, ), Santoro, (Santoro, N, Nicola)( 62, ), Albano, (Albano, F, Francesco)( 63, ), Castagnetti, (Castagnetti, F, Fausto), Ottaviani, (Ottaviani, E, Emanuela)(, 64, 65, ), Rambaldi, (Rambaldi, A, Alessandro)(, 66, 67, ), Stagno, (Stagno, F, Fabio)( 68, ), Molica, (Molica, S, Stefano)( 69, ), Biagiotti, (Biagiotti, C, Caterina)( 70, ), Scappini, (Scappini, B, Barbara)( 70, ), Lemoli, (Lemoli, R, Roberto)( 71, ), Iurlo, (Iurlo, A, Alessandra)(, 72, 73, ), Pungolino, (Pungolino, E, Ester)( 74, ), Menna, (Menna, G, Giuseppe), Pane, (Pane, F, Fabrizio)( 76, ), Gottardi, (Gottardi, E, Enrico)(, 77, 78, ), Rege-Cambrin, (Rege-Cambrin, G, Giovanna)(, 77, Binotto, (Binotto, G, Gianni)( 79, ), Putti, (Putti, Mc, Maria Caterina)( 80, ), Falzetti, (Falzetti, F, Franca)( 81, ), Visani, (Visani, G, Giuseppe)( 82, ), Galimberti, (Galimberti, S, Sara)( 83, ), Musto, (Musto, P, Pellegrino)( 84, ), Abruzzese, (Abruzzese, E, Elisabetta)( 85, ), Breccia, (Breccia, M, Massimo)( 86, ), Giona, (Giona, F, Fiorina)( 86, ), Chiusolo, (Chiusolo, P, Patrizia)( 87, ), Sica, (Sica, S, Simona)( 87, ), Fava, (Fava, C, Carmen)( 88, ), Ferrero, (Ferrero, D, Dario)( 88, ), Tiribelli, (Tiribelli, M, Mario)( 89, ), Bonifacio, (Bonifacio, M, Massimiliano)( 90, ), Griskevicius, (Griskevicius, L, Laimonas)( 91, ), Musteata, (Musteata, V, Vasile)( 92, ), Janssen, (Janssen, J, Jeroen)( 93, ), Prejzner, (Prejzner, W, Witold)( 94, ), Sacha, (Sacha, T, Tomasz)( 95, ), Waclaw, (Waclaw, J, Joanna)( 95, ), Almeida, (Almeida, Am, Antonio Medina)( 96, ), Kulikov, (Kulikov, S, Sergei)( 97, ), Turkina, (Turkina, A, Anna)( 97, ), Bogdanovic, (Bogdanovic, A, Andrija)( 98, ), Zupan, (Zupan, I, Irena)( 99, ), Marce, (Marce, S, Silvia)( 100, ), Cervantes, (Cervantes, F, Francisco)( 101, ), Steegmann, (Steegmann, Jl, Juan Luis)( 102, ), Kotlyarchuk, (Kotlyarchuk, K, Konstyantyn)( 103, ), Milner, (Milner, Bj, ( 104 ), Benedict J., Rose, (Rose, S, Susan)( 105, ), Clench, (Clench, T, Tim)( 106, ), Waits, (Waits, P, Paula)( 107, ), Austin, (Austin, S, Steve)( 108, ), Wickham, (Wickham, C, Caroline)( 109, ), Clark, (Clark, R, Richard)( 110, ), Apperley, (Apperley, J, Jane), Claudiani, (Claudiani, S, Simone)( 111, ), Foroni, (Foroni, L, Letizia)( 111, ), Szydlo, (Szydlo, R, Richard)( 111, ), Burt, (Burt, E, Emma)( 112, ), Bescoby, (Bescoby, R, Ruth)( 113, ), Cork, (Cork, L, Leanne)( 113, ), O'Brien, (O'Brien, S, Stephen)( 113, ), Green, (Green, B, Bethaney)( 114, ), Hawtree, (Hawtree, S, Sarah)( 114, ), Watson, (Watson, M, Mark)( 114, ), Bengio, (Bengio, Rm, Raquel Maria)( 115, ), Larripa, (Larripa, I, Irene)( 115, ), Pavlovsky, (Pavlovsky, C, Carolina)( 116, ), Moiraghi, (Moiraghi, B, Beatriz)( 117, ), Pinna, De, CAR (Requiao de Pinna, Cristiane Almeida)( 118, ), Magalhaes, GHR (Romani Magalhaes, Gustavo Henrique)( 119, ), Pagnano, (Pagnano, K, Katia)( 120, ), Funke, (Funke, V, Vaneuza)( 121, ), Tavares, (Tavares, Rs, Renato Sampaio)( 122, ), Prado, (Prado, A, Adriana)( 123, ), Azevedo, (Azevedo, Aa, Alita Andrade)( 124, ), Fogliatto, (Fogliatto, L, Laura)( 125, ), Bonecker, (Bonecker, S, Simone)( 126, ), Centrone, (Centrone, R, Renato)( 127, ), Moellman, (Moellman, A, Artur)( 128, ), Conchon, (Conchon, M, Monika)( 130, ), Centurion, (Centurion, Me, Maria Elida)( 131, ), (Prado, Ai, Ana-Ines)( 132, ), Lopez, (Lopez, Jl, ( 133 ), J. L., Petruzziello, (Petruzziello, F, Fara)( 75, ), Bendit, (Bendit, I, Israel), Baccarani M., Castagnetti F., Gugliotta G., Rosti G., Soverini S., Albeer A., and Pfirrmann M.

Subjects
Male, 0301 basic medicine, Cancer Research, bcr-abl, Fusion Proteins, bcr-abl, Global Health, 0302 clinical medicine, hemic and lymphatic diseases, 80 and over, Odds Ratio, Prevalence, Age Factor, Chronic, Young adult, Child, MOLECULAR RESPONSE, Leukemic, Aged, 80 and over, Leukemia, Hematology, Gene Expression Regulation, Leukemic, CHRONIC MYELOGENOUS LEUKEMIA, Age Factors, Myeloid leukemia, Middle Aged, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Human, Adult, Transcriptional Activation, medicine.medical_specialty, Adolescent, Immunology, IMATINIB MESYLATE, DENDRITIC CELLS, CML PATIENTS, Young Adult, 03 medical and health sciences, Myelogenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, BCR/ABL TRANSCRIPT, Preschool, CYTOGENETIC RESPONSE, Aged, Science & Technology, CHRONIC-PHASE, business.industry, Infant, Newborn, Fusion Proteins, ABL FUSION PROTEINS, P190 BCR-ABL, Infant, 1103 Clinical Sciences, Odds ratio, Newborn, medicine.disease, International BCR-ABL Study Group, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Imatinib mesylate, Gene Expression Regulation, BCR-ABL Positive, business, Chronic myelogenous leukemia
Abstract

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associatedwith gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission.

Published
2019

12. Observational study of chronic myeloid leukemia italian patients who discontinued tyrosine kinase inhibitors in clinical practice

Author

Fava, C, Rege-Cambrin, G, Dogliotti, I, Cerrano, M, Berchialla, P, Dragani, M, Rosti, G, Castagnetti, F, Gugliotta, G, Martino, B, Gambacorti-Passerini, C, Abruzzese, E, Elena, C, Pregno, P, Gozzini, A, Capodanno, I, Bergamaschi, M, Crugnola, M, Bocchia, M, Galimberti, S, Rapezzi, D, Iurlo, A, Cattaneo, D, Latagliata, R, Breccia, M, Cedrone, M, Santoro, M, Annunziata, M, Levato, L, Stagno, F, Cavazzini, F, Sgherza, N, Giai, V, Luciano, L, Russo, S, Musto, P, Caocci, G, Sora, F, Iuliano, F, Lunghi, F, Specchia, G, Pane, F, Ferrero, D, Baccarani, M, Saglio, G, Fava C., Rege-Cambrin G., Dogliotti I., Cerrano M., Berchialla P., Dragani M., Rosti G., Castagnetti F., Gugliotta G., Martino B., Gambacorti-Passerini C., Abruzzese E., Elena C., Pregno P., Gozzini A., Capodanno I., Bergamaschi M., Crugnola M., Bocchia M., Galimberti S., Rapezzi D., Iurlo A., Cattaneo D., Latagliata R., Breccia M., Cedrone M., Santoro M., Annunziata M., Levato L., Stagno F., Cavazzini F., Sgherza N., Giai V., Luciano L., Russo S., Musto P., Caocci G., Sora F., Iuliano F., Lunghi F., Specchia G., Pane F., Ferrero D., Baccarani M., Saglio G., Fava, C, Rege-Cambrin, G, Dogliotti, I, Cerrano, M, Berchialla, P, Dragani, M, Rosti, G, Castagnetti, F, Gugliotta, G, Martino, B, Gambacorti-Passerini, C, Abruzzese, E, Elena, C, Pregno, P, Gozzini, A, Capodanno, I, Bergamaschi, M, Crugnola, M, Bocchia, M, Galimberti, S, Rapezzi, D, Iurlo, A, Cattaneo, D, Latagliata, R, Breccia, M, Cedrone, M, Santoro, M, Annunziata, M, Levato, L, Stagno, F, Cavazzini, F, Sgherza, N, Giai, V, Luciano, L, Russo, S, Musto, P, Caocci, G, Sora, F, Iuliano, F, Lunghi, F, Specchia, G, Pane, F, Ferrero, D, Baccarani, M, Saglio, G, Fava C., Rege-Cambrin G., Dogliotti I., Cerrano M., Berchialla P., Dragani M., Rosti G., Castagnetti F., Gugliotta G., Martino B., Gambacorti-Passerini C., Abruzzese E., Elena C., Pregno P., Gozzini A., Capodanno I., Bergamaschi M., Crugnola M., Bocchia M., Galimberti S., Rapezzi D., Iurlo A., Cattaneo D., Latagliata R., Breccia M., Cedrone M., Santoro M., Annunziata M., Levato L., Stagno F., Cavazzini F., Sgherza N., Giai V., Luciano L., Russo S., Musto P., Caocci G., Sora F., Iuliano F., Lunghi F., Specchia G., Pane F., Ferrero D., Baccarani M., and Saglio G.

Abstract

It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TKI than with imatinib (P<0.001). Eighty-eight percent of patients discontinued as per clinical practice, and reasons for stopping treatment were: toxicity (20%), pregnancy (6%), and shared decision between treating physician and patient (62%). After a median follow up of 34 months (range, 12-161) overall estimated TFR was 62% (95%CI: 56;68). At 12 months, TFR was 68% (95%CI: 62;74) for imatinib, 73% (95%CI: 64;83) for second generation TKI. Overall median time to restart treatment was six months (IQR 4;11). No progressions occurred. Although our study has the limitation of a retrospective study, our experience within the Italian population confirms that discontinuation of imatinib and second generation TKI is feasible and safe in clinical practice

Published
2019

13. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

Castagnetti, F., Gugliotta, G., Baccarani, M., Breccia, M., Specchia, G., Levato, L., Abruzzese, E., Rossi, G., Iurlo, A., Martino, B., Pregno, P., Stagno, F., Cuneo, A., Bonifacio, M., Gobbi, M., Russo, D., Gozzini, A., Tiribelli, M., de Vivo, A., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Salvi, F., Pini, M., Leoni, P., Rupoli, S., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Albano, F., Russo Rossi, A., Rambaldi, A., Intermesoli, T., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, MT., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Malagola, M., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., Storti, S., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Impera, S., Molica, S., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cavazzini, F., Bosi, A., Santini, V., Capalbo, SF., Spinosa, G., Pierri, I., Bergamaschi, M., Carella, AM., Bacigalupo, A., De Blasio, A., Ciccone, F., Di Renzo, N., Musolino, C., Russo, S., Cortelezzi, A., Morra, E., Pungolino, EM., Luppi, M., Marasca, R., Pogliani, EM., Gambacorti-Passerini, C., Luciano, L., Ferrara, F., Annunziata, M., Latte, G., Noli, D., Rege-Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Aversa, F., Crugnola, M., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidori, A., Fioritoni, G., Di Lorenzo, R., Vallisa, D., Trabacchi, E., Petrini, M., Galimberti, S., Pizzuti, M., Zaccaria, A., Salvucci, M., Ronco, F., Ielo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Musto, P., De Stefano, V., Sica, S., Latagliata, R., De Fabritiis, P., Trawiska, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Petti, MC., Pisani, F., Tafuri, A., Montefusco, E., Iuliano, F., Dore, F., Pardini, S., Bocchia, M., Defina, M., Liberati, AM., Luzzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Gherlinzoni, F., Calistri, E., Fanin, R., Pizzolo, G., Meneghini, V., Rodighiero, F., and DʼEmilio, A.

Published
2015
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14. Chronic myeloid leukemia management at the time of the COVID-19 pandemic in Italy. A campus CML survey

Author

Breccia, M., Abruzzese, E., Bocchia, M., Bonifacio, M., Castagnetti, F., Fava, C., Galimberti, S., Gozzini, A., Gugliotta, G., Iurlo, A., Latagliata, R., Luciano, L., Pregno, P., Rege-Cambrin, G., Rosti, G., Stagno, F., Tiribelli, M., Foa, R., Saglio, G., Mariacristina, M. M., Isabella, C., Vincenzo, A., Federica, S., Debora, L., Mario, A., Immacolata, A., Alessandra, M., Rosaria, S., Chiara, E., Sara, B., Rita, S. A., Sabrina, L. -C., Agostino, T., Francesco, C., Giovanni, C., Alessandro, L., Davide, R., Michele, P., Gianni, B., Tamara, I., Alessandro, M., Elena, C., Monica, C., Mariella, D. A., Germana, B., Francesca, L., Iolanda -Donatella, V., Grazia, S., Luca, F., Sabina, R., Gaetano, L. B., Breccia M., Abruzzese E., Bocchia M., Bonifacio M., Castagnetti F., Fava C., Galimberti S., Gozzini A., Gugliotta G., Iurlo A., Latagliata R., Luciano L., Pregno P., Rege-Cambrin G., Rosti G., Stagno F., Tiribelli M., Foa R., Saglio G., MariaCristina M.M., Isabella C., Vincenzo A., Federica S., Debora L., Mario A., Immacolata A., Alessandra M., Rosaria S., Chiara E., Sara B., Rita S.A., Sabrina L.-C., Agostino T., Francesco C., Giovanni C., Alessandro L., Davide R., Michele P., Gianni B., Tamara I., Alessandro M., Elena C., Monica C., Mariella D.A., Germana B., Francesca L., Iolanda -Donatella V., Grazia S., Luca F., Sabina R., and Gaetano L.B.

Subjects
Cancer Research, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Protein Kinase Inhibitor, Time-to-Treatment, Betacoronavirus, Myelogenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Surveys and Questionnaires, Correspondence, Pandemic, Surveys and Questionnaire, COVID-19, Coronavirus Infections, Disease Management, Humans, Infection Control, Italy, Pandemics, Practice Guidelines as Topic, Protein Kinase Inhibitors, SARS-CoV-2, Telemedicine, Medicine, Viral, Chronic, Disease management (health), Chronic myeloid leukaemia, Leukemia, Betacoronaviru, Coronavirus Infection, business.industry, Myeloid leukemia, Pneumonia, Hematology, medicine.disease, Oncology, Family medicine, BCR-ABL Positive, business, Haematological diseases, Human
Abstract

No abstract available.

Published
2020

15. Extensive air showers and diffused Cherenkov light detection: The ULTRA experiment

Author

Agnetta, G., Assis, P., Biondo, B., Brogueira, P., Cappa, A., Catalano, O., Chauvin, J., D’Alí Staiti, G., Dattoli, M., Espirito-Santo, M.C., Fava, L., Galeotti, P., Giarrusso, S., Gugliotta, G., La Rosa, G., Lebrun, D., Maccarone, M.C., Mangano, A., Melo, L., Moreggia, S., Pimenta, M., Russo, F., Saavedra, O., Segreto, A., Silva, J.C., Stassi, P., Tomè, B., Vallania, P., and Vigorito, C.

Published
2007
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16. outcome of very elderly chronic myeloid leukemia patients treated with imatinib frontline

Author

Crugnola, M, Castagnetti, F, Breccia, M, Ferrero, D, Trawinska, Mm, Abruzzese, E, Annunziata, M, Stagno, F, Tiribelli, M, Binotto, G, Bonifacio, M, Fava, C, Iurlo, A, Bucelli, C, Mansueto, G, Gozzini, A, Falzetti, F, Montefusco, E, Crisà, E, Gugliotta, G, Russo, S, Cedrone, M, Russorossi, A, Pregno, P, Isidori, A, Mauro, E, Atelda, R, Giglio, G, Celesti, F, Sora', Federica, Storti, S, D'Addosio, A, Galimberti, S, Orlandi, E, Calistri, E, Bocchia, M, Cavazzini, F, Cambrin, Gr, Orofino, N, Luciano, L, Sgherza, N, Rosti, G, Latagliata, R, Capodanno, I, Sora, Federica (ORCID:0000-0002-9607-5298), Crugnola, M, Castagnetti, F, Breccia, M, Ferrero, D, Trawinska, Mm, Abruzzese, E, Annunziata, M, Stagno, F, Tiribelli, M, Binotto, G, Bonifacio, M, Fava, C, Iurlo, A, Bucelli, C, Mansueto, G, Gozzini, A, Falzetti, F, Montefusco, E, Crisà, E, Gugliotta, G, Russo, S, Cedrone, M, Russorossi, A, Pregno, P, Isidori, A, Mauro, E, Atelda, R, Giglio, G, Celesti, F, Sora', Federica, Storti, S, D'Addosio, A, Galimberti, S, Orlandi, E, Calistri, E, Bocchia, M, Cavazzini, F, Cambrin, Gr, Orofino, N, Luciano, L, Sgherza, N, Rosti, G, Latagliata, R, Capodanno, I, and Sora, Federica (ORCID:0000-0002-9607-5298)

Abstract

Very elderly (> 75 years) chronic myeloid leukaemia (CML) patients at diagnosis are sometimes treated with different doses of imatinib (IM) based on concomitant diseases and physicians' judgement. However, data on long-term follow-up of these patients are still lacking. To investigate treatment response and outcome, we retrospectively revised an Italian database of 263 very elderly CML patients receiving IM from the time of diagnosis. Median age at diagnosis was 78.5 years and 56% of patients had 2 or 3 comorbidities. A complete haematological and cytogenetic response were achieved in 244 (92.8%) and 184 (69.9%) patients, respectively. In 148 cases (56.2%), a major molecular response was observed, which was deep in 63 cases (24%). A blastic phase occurred in 11 patients (4.2%). After a median follow-up of 45.0 months, 93 patients have died (9 from disease progression) and 104 (39.5%) are still in treatment with IM. Incidence of grades 3-4 haematological and non-haematological toxicity was similar to those reported in younger patients. Five-year event-free survival was 54.5% and 45.2% in patients ≤ 80 years and > 80 years, respectively (p = 0.098). Five years OS was 75.7% and 61.6% in patients ≤80 years and > 80 years, respectively (p = 0.003). These findings show that IM plays an important role in frontline treatment of very elderly CML patients without increased toxicity and any effort to treat these patients with standard doses should be made in order to achieve responses as in younger subjects

Published
2019

18. Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party

Author

Gugliotta, G, Castagnetti, F, Palandri, F, Breccia, M, Intermesoli, T, Capucci, A, Martino, B, Pregno, P, Rupoli, S, Ferrero, D, Gherlinzoni, F, Montefusco, E, Bocchia, M, Tiribelli, M, Pierri, Ivana, Grifoni, F, Marzocchi, G, Amabile, M, Testoni, N, Martinelli, G, Alimena, G, Pane, F, Saglio, G, Baccarani, M, Rosti, G, Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working Party, Gugliotta, G, Castagnetti, F, Palandri, F, Breccia, M, Intermesoli, T, Capucci, A, Martino, B, Pregno, P, Rupoli, S, Ferrero, D, Gherlinzoni, F, Montefusco, E, Bocchia, M, Tiribelli, M, Pierri, I, Grifoni, F, Marzocchi, G, Amabile, M, Testoni, N, Martinelli, G, Alimena, G, Pane, Fabrizio, Saglio, G, Baccarani, M, Rosti, G, Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working, Party, Gugliotta G., Castagnetti F., Palandri F., Breccia M., Intermesoli T., Capucci A., Martino B., Pregno P., Rupoli S., Ferrero D., Gherlinzoni F., Montefusco E., Bocchia M., Tiribelli M., Pierri I., Grifoni F., Marzocchi G., Amabile M., Testoni N., Martinelli G., Alimena G., Pane F., Saglio G., Baccarani M., and Rosti G.

Subjects
Myeloid, Male, chronic myeloid leukemia, imatinib, elderly, Biochemistry, Piperazines, hemic and lymphatic diseases, 80 and over, Young adult, Aged, 80 and over, Leukemia, Mortality rate, Myeloid leukemia, Hematology, Middle Aged, Phase III as Topic, Survival Rate, Treatment Outcome, Benzamides, Leukemia, Myeloid, Chronic-Phase, Disease Progression, Imatinib Mesylate, Female, Complete Hematologic Response, Adult, medicine.medical_specialty, Adolescent, Immunology, Alpha interferon, Antineoplastic Agents, Young Adult, Clinical Trials, Phase II as Topic, Internal medicine, medicine, Humans, Clinical Trials, bone-marrow-transplantation, chronic myelogenous leukemia, complete cytogenetic response, early chronic phase, elderly-patients, european-leukemianet, interferon-alpha, line treatment, mesylate therapy, patients receiving imatinib, Survival rate, Aged, business.industry, Clinical Trials, Phase III as Topic, Health Surveys, Pyrimidines, Phase II as Topic, Cell Biology, medicine.disease, Surgery, Imatinib mesylate, Chronic-Phase, business, CHRONIC MYELOID LEUKEMIA (CML), Chronic myelogenous leukemia
Abstract

The median age of chronic myeloid leukemia (CML) patients is ∼ 60 years, and age is still considered an important prognostic factor, included in Sokal and EURO risk scores. However, few data are available about the long-term outcome of older patients treated with imatinib (IM) frontline. We analyzed the relationship between age and outcome in 559 early chronic-phase CML patients enrolled in 3 prospective clinical trials of Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working Party, treated frontline with IM, with a median follow-up of 60 months. There were 115 older patients (≥ 65 years; 21%). The complete cytogenetic and major molecular response rates were similar in the 2 age groups. In older patients, event-free survival (55% vs 67%), failure-free survival (78% vs 92%), progression-free survival (62% vs 78%), and overall survival (75% vs 89%) were significantly inferior (all P < .01) because of a higher proportion of deaths that occurred in complete hematologic response, therefore unrelated to CML progression (15% vs 3%, P < .0001). The outcome was similar once those deaths were censored. These data show that response to IM was not affected by age and that the mortality rate linked to CML is similar in both age groups. This trial was registered at www.clinicaltrials.gov as #NCT00514488 and #NCT00510926.

Published
2011

20. S123 SETD2 LOSS OF FUNCTION IS A RECURRENT EVENT IN ADVANCED-PHASE CHRONIC MYELOID LEUKEMIA INDUCED BY POST-TRANSLATIONAL MECHANISMS THAT CAN BE THERAPEUTICALLY TARGETED

Author

Mancini, M., primary, De Santis, S., additional, Monaldi, C., additional, Bavaro, L., additional, Martelli, M., additional, Castagnetti, F., additional, Gugliotta, G., additional, Rosti, G., additional, Fontana, M.C., additional, Dan, E., additional, Sinigallia, B., additional, Iurlo, A., additional, Orofino, N., additional, Abbruzzese, E., additional, Salvucci, M., additional, Pregno, P., additional, Gozzini, A., additional, Crugnola, M., additional, Albano, F., additional, Bonifacio, M., additional, Calistri, E., additional, Tiribelli, M., additional, Binotto, G., additional, Imovilli, A., additional, Trabacchi, E., additional, Galimberti, S., additional, Baratè, C., additional, Tenti, E., additional, Baccarani, M., additional, Martinelli, G., additional, Cavo, M., additional, and Soverini, S., additional

Published
2019
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21. ESTABLISHING A NATIONAL NETWORK OF LABORATORIES USING NEXT GENERATION AMPLICON DEEP SEQUENCING FOR BCR-ABL1 KINASE DOMAIN MUTATION SCREENING: THE 'NEXT-IN-CML' STUDY

Author

Soverini, S., Benedittis, C., Bavaro, L., Martelli, M., Stella, S., Iurlo, A., Orofino, N., Barate, C., Galimberti, S., Sica, S., Sora, F., Rossi, A. Russo, Albano, F., Ciceri, F., Lunghi, F., Castagnetti, F., Gugliotta, G., Tenti, E., Rosti, G., CRISTINA PAPAYANNIDIS, Stagno, F., Vigneri, P., Serra, A., Saglio, G., Carnuccio, F., Pane, F., Errichiello, S., Annunziata, M., Breccia, M., Abruzzese, E., Bonifacio, M., Novella, E., Di Bona, E., Sancetta, R., Calistri, E., Spinosa, G., D Adda, M., Capodanno, I., Baccarani, M., Cavo, M., and Martinelli, G.

Published
2017

22. Sopravvivenza libera da trombosi in 734 pazienti con trombocitemia essenziale (WHO 2016) stratificati secondo lo score 'Revised International Prognostic Score for Thrombosis in Essential Thrombocythemia (R-IPSET-Th)'. Studio del Regostro ItalianoTrombocitemie (RIT)

Author

Gugliotta, L, Iurlo, A, Gugliotta, G, Tieghi, A, Gaidano, G, Dragani, A, Scalzulli, P, Martinelli, V, Martino, B, Randi, Ml, Cattaneo, D, Appolloni, V, Maschio, N, Langella, M, Santoro, C, Rago, A, Cacciola, Emma, Cacciola, Rossella Rosaria, Caocci, G, Plebani, S, Santoro, U, Vianelli, N, Mazzucconi, Mg, Specchia, G, Passamonti, F, and Vannucchi, Am

Published
2017

24. The BCR-ABL1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib

Author

Castagnetti, F, Gugliotta, G, Breccia, M, Iurlo, A, Levato, L, Albano, F, Vigneri, Paolo, Abruzzese, E, Rossi, G, Rupoli, S, Cavazzini, F, Martino, B, Orlandi, E, Pregno, P, Annunziata, M, Usala, E, Tiribelli, M, Sica, S, Bonifacio, M, Fava, C, Gherlinzoni, F, Bocchia, M, Soverini, S, Bochicchio, Mt, Cavo, M, Giovanni, M, Saglio, G, Pane, F, Baccarani, M, Rosti, G, on behalf of the GIMEMA CML Working Party, Castagnetti, Fausto, Gugliotta, Gabriele, Breccia, Massimo, Iurlo, Alessandra, Levato, Luciano, Albano, Francesco, Vigneri, Paolo, Abruzzese, Elisabetta, Rossi, Giuseppe, Rupoli, Serena, Cavazzini, Francesco, Martino, Bruno, Orlandi, Ester, Pregno, Patrizia, Annunziata, Mario, Usala, Emilio, Tiribelli, Mario, Sica, Simona, Bonifacio, Massimiliano, Fava, Carmen, Gherlinzoni, Filippo, Bocchia, Monica, Soverini, Simona, Bochicchio, Maria Teresa, Cavo, Michele, Giovanni, Martinelli, Saglio, Giuseppe, Pane, Fabrizio, Baccarani, Michele, and Rosti, Gianantonio

Subjects
Oncology, Male, Transcription, Genetic, bcr-abl, Fusion Proteins, bcr-abl, BCR-ABL1, Chronic myeloid leukemia, Philadelphia chromosome, imatinib, prognosis, transcript type, cytogenetic response, 0302 clinical medicine, CHRONIC-PHASE, CYTOGENETIC RESPONSE, MOLECULAR-BIOLOGY, END-POINTS, 800 MG, RECOMMENDATIONS, SURVIVAL, CML, BREAKPOINT, E13A2, hemic and lymphatic diseases, 80 and over, Medicine, molecular biology, Chronic, Young adult, Prospective cohort study, Aged, 80 and over, breakpoint, Leukemia, Philadelphia Chromosome Positive, Myeloid leukemia, Hematology, Middle Aged, Prognosis, Treatment Outcome, 030220 oncology & carcinogenesis, Imatinib Mesylate, Female, Transcription, prognosi, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Socio-culturale, Antineoplastic Agents, Aged, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplasm Grading, Neoplasm Staging, Proportional Hazards Models, Protein Kinase Inhibitors, Young Adult, survival, 03 medical and health sciences, Genetic, Internal medicine, end points, chronic phase, cytogenetic response, molecular biology, end points, recommendations, survival, CML, breakpoint, chronic phase, business.industry, Proportional hazards model, Fusion Proteins, Imatinib, medicine.disease, Settore MED/15 - MALATTIE DEL SANGUE, Immunology, recommendations, BCR-ABL Positive, business, Myelogenous, 030215 immunology
Abstract

The most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed. A qualitative PCR was performed at baseline: 52% patients had a e14a2 transcript, 37% a e13a2 transcript, 11% co-expressed both transcripts and 1% had other rare transcripts. The median follow-up was 76 months (95% of the patients had at least a 5-year observation). The complete cytogenetic response rates were comparable in e14a2 and e13a2 patients. The median time to MR(3.0) (6 and 12 months) and MR(4.0) (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR(3.0) (88% and 83%, p

Published
2017

26. LONG-TERM FOLLOW-UP IN VERY ELDERLY PATIENTS WITH CHRONIC MYELOID LEUKEMIA TREATED WITH IMATINIB FRONTLINE

Author

Crugnola, M, Latagliata, R, Breccia, M, Ferrero, D, Trawinska, Mm, Castagnetti, F, Annunziata, M, Stagno, F, Tiribelli, M, Binotto, G, Fava, C, Crisa, E, Mansueto, G, Gozzini, A, Falzetti, F, Montefusco, E, Iurlo, A, Russo, S, Cedrone, M, Rossi, Ar, Gugliotta, G, Pregno, P, Isidori, A, Mauro, E, Atelda, R, Giglio, G, Celesti, F, Sora, F, Storti, S, D'Addosio, Am, Galimberti, S, Orlandi, E, Calistri, E, Bocchia, M, Cavazzini, F, Cambrin, Gr, Luciano, L, Abruzzese, E, and Capodanno, I

Published
2017

28. Observational Study of CML Italian Patients Who Discontinued TKIs

Author

Fava, C, Rege-Carmbrin, G, Dogliotti, I, Cerrano, M, Berchialla, P, Rosti, G, Castagnetti, F, Gugliotta, G, Martino, B, Gambacorti-Passerini, C, Abruzzese, E, Orlandi, Em, Elena, C, Pregno, P, Gozzini, A, Avanzini, P, Bergamaschi, M, Crugnola, M, Bocchia, M, Galimberti, S, Rapezzi, D, Iurlo, A, Cattaneo, D, Latagliata, R, Breccia, M, Cedrone, M, Santoro, M, Annunziata, M, Levato, L, Stagno, F, Cavazzini, F, Sgherza, N, Giai, V, Luciano, L, Russo, S, Musto, P, Caocci, G, Sora, F, Iuliano, F, Lunghi, F, Specchia, G, Pane, F, Baccarani, M, Ferrero, D, and Saglio, G

Published
2017

29. Use of trans-labial ultrasound in the diagnosis of female urethral diverticula: A diagnostic option to be strongly considered

Author

Gugliotta, G, Polito, S, Speciale, P, Adile, B., Calagna, Gloria, ADILE, Giorgio, PERINO, Antonino, Gugliotta, G, Calagna, G, Adile, G, Polito, S, Speciale, P, Perino, A, and Adile, B.

Subjects
urethral pathology, ultrasound, trans-labial ultrasound, Settore MED/40 - Ginecologia E Ostetricia, sonographic diagnosi, urethral diverticulum
Abstract

AIM: To demonstrate effectiveness of trans-labial ultrasound (TL-US) in the evaluation of female urethral diverticula (UD). METHODS: In the study period, 20 UD were diagnosed and treated. All data on demographic characteristics, presenting symptoms, physical examination findings, diagnostic and operative procedures, were considered. Patients were referred to TL-US for diverticular evaluation, using a 2D 7.5-MHz endfire probe. For each UD, size, complexity, echogenicity content, and presence of diverticular neck were considered. Follow-up controls were carried out at 1, 6 and 12 months after surgery, to evaluate outcome and need for further intervention. RESULTS: Mean patient age was 46 years (range, 35-55 years) and mean parity was 1 (range, 0-3). The principal symptoms associated with the diverticular mass was dysuria (25%). In all evaluated cases, UD was single (simple in 15 cases and complex in 5). The mean size of the diverticula was 28 mm (range, 8-50 mm). Nineteen diverticula were diagnosed on TL-US, and urethrocystoscopy was carried out for confirmation. Treatment consisted of diverticulectomy. At 1-, 6- and 12-month follow up after surgery, TL-US showed no recurrence of UD in any of the patients. CONCLUSIONS: TL-US is a valid, mini-invasive and reproducible method to diagnose UD.

Published
2015

30. Role of autologous stem cell transplantation or salvage chemotherapy in relapsed/refractory classical Hodgkin lymphoma patients after immune checkpoint inhibitors.

Author

Pellegrini, C., Casadei, B., Sutto, E., Cantelli, M., Argnani, L., Broccoli, A., Gugliotta, G., Stefoni, V., Nanni, L., Carella, M., Zoli, S., Coppola, P. E., Lolli, G., Morigi, A., Bagnato, G., Gentilini, M., and Zinzani, P. L.

Subjects
STEM cell transplantation, IMMUNE checkpoint inhibitors, HODGKIN'S disease, CANCER chemotherapy
Abstract

In addition, treatment with CPI, regardless of its success, appears to promote sensitization to subsequent chemotherapy regimen in a setting of heavily pretreated and chemorefractory patients. B Introduction: b Programmed death-1 (PD1) blockade is an efficient and safe therapeutic option in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). [Extracted from the article]

Published
2023
Full Text
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31. BEGEV as salvage regimen in first setting for relapsed/refractory classical Hodgkin lymphoma.

Author

Carella, M., Argnani, L., Coppola, P. E., Nanni, L., Zoli, S., Cantelli, M., Morigi, A., Gentilini, M., Lolli, G., Bagnato, G., Sutto, E., Gugliotta, G., Casadei, B., Pellegrini, C., Stefoni, V., Broccoli, A., and Zinzani, P. L.

Subjects
HODGKIN'S disease, STEM cell transplantation
Abstract

Six patients had an early BEGEV discontinuation due toxicity, but they were still able to perform ASCT with a CR. B Introduction: b One of the most critical issues in the management of Hodgkin lymphoma (HL) patients who resulted as primary relapsed or refractory is to obtain a minimal disease status before autologous stem cell transplantation (ASCT) with a salvage regimen able to induce this status without severe toxicity. [Extracted from the article]

Published
2023
Full Text
View/download PDF

32. Pleural effusion and molecular response in dasatinib-treated chronic myeloid leukemia patients in a real-life Italian multicenter series.

Author

Iurlo, A, Galimberti, S, Abruzzese, E, Annunziata, M, Bonifacio, M, Latagliata, R, Pregno, P, Ferrero, D, Sora', Federica, Orlandi, Em, Fava, Chiara, Cattaneo, Davide, Bucelli CBinotto, G, Pungolino, E, Tiribelli, M, Gozzini, A, Gugliotta, G, Castagnetti, F, Stagno, F, Rege-Cambrin, G, Martino, B, Luciano, L, Breccia, M, Sica, Simona, Bocchia, M, Pane, F, Saglio, G, Rosti, G, Specchia, G, Cortelezzi, A, Baccarani, M, Sorà F (ORCID:0000-0002-9607-5298), Sica S (ORCID:0000-0003-2426-3465), Iurlo, A, Galimberti, S, Abruzzese, E, Annunziata, M, Bonifacio, M, Latagliata, R, Pregno, P, Ferrero, D, Sora', Federica, Orlandi, Em, Fava, Chiara, Cattaneo, Davide, Bucelli CBinotto, G, Pungolino, E, Tiribelli, M, Gozzini, A, Gugliotta, G, Castagnetti, F, Stagno, F, Rege-Cambrin, G, Martino, B, Luciano, L, Breccia, M, Sica, Simona, Bocchia, M, Pane, F, Saglio, G, Rosti, G, Specchia, G, Cortelezzi, A, Baccarani, M, Sorà F (ORCID:0000-0002-9607-5298), and Sica S (ORCID:0000-0003-2426-3465)

Abstract

Pleural effusion (PE) represents the leading cause of dasatinib (DAS) discontinuation. However, the pathogenic mechanism of this adverse event (AE) is unknown and its management unclear. We investigated if a DAS dose reduction after the first PE would prevent the recurrence of this AE. We retrospectively collected data on all the cases of PE in CML-chronic phase (CP) DAS-treated patients from November 2005 to February 2017 in 21 Italian hematological centers. We identified 196 cases of PE in a series of 853 CML-CP DAS-treated patients (incidence 23.0%). DAS starting dose was 100 mg/day in 70.4% of patients, less than 100 mg/day in 14.3%, and more than 100 mg/day in the remaining cases. Median time from DAS start to PE was 16.6 months. At first PE development, 28.6% of patients were in MMR, and 37.8% in deep molecular response (DMR). DAS was temporary interrupted in 71.9% of cases, with a dose reduction in 59.2%. Recurrence was observed in 59.4% of the cases. Treatment was definitively discontinued due to PE in 29.1% of the cases. Interestingly, among patients whose DAS dosage was reduced, 59.5% experienced PE recurrence. DAS dose reduction after the first episode of PE did not prevent recurrence of this AE. Therefore, once a MMR or a DMR is achieved, different strategies of DAS dose management can be proposed prior to the development of PE, such as daily dose reduction or, as an alternative option, an on/off treatment with a weekend drug holiday.

Published
2017

33. A population-based study of chronic myeloid leukemia patients treated with imatinib in first line

Author

Castagnetti, F, DI RAIMONDO, Francesco, De Vivo, A, Spitaleri, A, Gugliotta, G, Fabbiano, F, Capodanno, I, Mannina, D, Salvucci, M, Antolino, A, Marasca, R, Musso, M, Crugnola, M, Impera, S, Trabacchi, E, Musolino, C, Cavazzini, F, Mineo, G, Tosi, P, Tomaselli, C, Rizzo, M, Siragusa, S, Fogli, M, Ragionieri, R, Zironi, A, Soverini, S, Martinelli, G, Cavo, M, Vigneri, Paolo, Stagno, F, Rosti, G, Baccarani, M., Castagnetti, Fausto, Di Raimondo, Francesco, De Vivo, Antonio, Spitaleri, Antonio, Gugliotta, Gabriele, Fabbiano, Francesco, Capodanno, Isabella, Mannina, Donato, Salvucci, Marzia, Antolino, Agostino, Marasca, Roberto, Musso, Maurizio, Crugnola, Monica, Impera, Stefana, Trabacchi, Elena, Musolino, Caterina, Cavazzini, Francesco, Mineo, Giuseppe, Tosi, Patrizia, Tomaselli, Carmela, Rizzo, Michele, Siragusa, Sergio, Fogli, Miriam, Ragionieri, Riccardo, Zironi, Alessandro, Soverini, Simona, Martinelli, Giovanni, Cavo, Michele, Vigneri, Paolo, Stagno, Fabio, Rosti, Gianantonio, and Baccarani, Michele

Subjects
Male, Leukemia, Chronic myeloid leukemia, Hematology, Middle Aged, Disease-Free Survival, NO, Hematology, Chronic myeloid leukemia, imatinib, Disease-Free Survival, Female, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Male, Middle Aged, Prospective Studies, Protein Kinase Inhibitors, Treatment Outcome, Treatment Outcome, imatinib, Female, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Prospective Studies, Protein Kinase Inhibitors, BCR-ABL Positive, Chronic, Myelogenous
Abstract

Chronic myeloid leukemia (CML) treatment is based on company-sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first-line therapy. These studies included patients selected according to many inclusion–exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real-life), inclusion–exclusion criteria do not exist, and the treatment outcome does not only depend on the choice of first-line TKI but also on second- and third-line TKIs. To investigate in a real-life setting the response and the outcome on first-line imatinib, with switch to second generation TKIs in case of unsatisfying response or intolerance, we analyzed all newly diagnosed patients (N = 236), living in two Italian regions, registered in a prospective study according to population-based criteria and treated front-line with imatinib. A switch from imatinib to second-generation TKIs was reported in 14% of patients for side effects and in 24% for failure or suboptimal response, with an improvement of molecular response in 57% of them. The 5-year overall survival (OS) and leukemia-related survival (LRS) were 85% and 93%, respectively; the 4-year rates of MR3.0 and MR4.0 were 75% and 48%, respectively. Cardiovascular complications were reported in 4% of patients treated with imatinib alone and in 6% of patients receiving nilotinib as second-line. Older age (≥70 years) affected OS, but not LRS. These data provide an unbiased reference on the CML management and on the results of TKI treatment in real-life, according to ELN recommendations, using imatinib as first-line treatment and second-generation TKIs as second-line therapy. Am. J. Hematol. 92:82–87, 2017. © 2016 Wiley Periodicals, Inc.

Published
2016

34. Deep sequencing of the bcr-abl kinase domain reveals a high frequency of bcr-abl35-ins insertion/truncation mutation in chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia patients

Author

De Benedittis C, Soverini S, Machova Polakova K, Brouckova A, Rosti G, Castagnetti F, Gugliotta G, Papayannidis C, Klamova H, Iacobucci I, Russo D, Martínez Lopez J, Barrio S, Baccarani M, Cavo M, Martinelli G, and De Benedittis C, Soverini S, Machova Polakova K, Brouckova A, Rosti G, Castagnetti F, Gugliotta G, Papayannidis C, Klamova H, Iacobucci I, Russo D, Martínez Lopez J, Barrio S, Baccarani M, Cavo M, Martinelli G

Subjects
bcr-abl35-in, truncation, Deep sequencing, chronic myeloid leukemia, bcr-abl kinase domain mutation, Philadelphia positive acute lymphoblastic leukemia, insertion
Published
2014

35. 'Accordo di collaborazione per l'avvio delle reti speciali di cui al decreto legislativo 155/2010 tra il Ministero dell'Ambiente e della Tutela del Territorio e del Mare, il Consiglio Nazionale delle Ricerche (CNR), l'Agenzia Nazionale per le nuove tecnologie, l'energia e lo sviluppo economico sostenibile (ENEA) e l'Istituto Superiore di Sanità (ISS), stipulato il 23/12/2010'

Author

Pirrone N., Cecinato A., Perrino C., Guerriero E., Sprovieri F., Bencardino M., Fardelli A., Annunziata L., Dirodi M., Gugliotta G., Leonardi C., Magnavita G., Modesti A., Sollazzo I., Poggi C., and Mazziotti C.

Subjects
Reti speciali, Qualità dell'aria
Abstract

IX S.A.L. Rapporto RT/CNR/IIA/2676 del 22 settembre 2016, Rapporto predisposto nell'ambito dell'accordo sulle reti speciali Accordo di collaborazione per l'avvio delle reti speciali di cui al decreto legislativo 155/2010 tra il Ministero dell'Ambiente e della Tutela del Territorio e del Mare, il Consiglio Nazionale delle Ricerche (CNR), l'Agenzia Nazionale per le nuove tecnologie, l'energia e lo sviluppo economico sostenibile (ENEA) e l'Istituto Superiore di Sanità (ISS), stipulato il 23/12/2010

Published
2016

36. TREATMENT, RESPONSE, AND OUTCOME IN UNSELECTED ELDERLY PATIENTS WITH NEWLY DIAGNOSED, CHRONIC PHASE (CP), PHILADELPHIA CHROMOSOME-POSITIVE (PH plus ) CHRONIC MYELOID LEUKEMIA

Author

Gugliotta, G, Stagno, F, De Vivo, A, Spitalieri, A, Castagnetti, F, Fabbiano, F, Capodanno, I, Mannina, D, Salvucci, M, Antolino, A, Marasca, R, Musso, M, Crugnola, M, Consoli, U, Trabacchi, E, Musolino, C, Cavazzini, F, Longo, G, Tosi, P, Cardinale, G, Rizzo, M, Soverini, S, Martinelli, G, Cavo, M, Vigneri, Paolo, Rosti, G, DI RAIMONDO, Francesco, and Baccarani, M.

Subjects
Socio-culturale
Published
2016

37. IMATINIB FIRST-LINE WITH SWITCH TO 2ND GENERATION TYROSINE KINASE INHIBITORS IN CASE OF FAILURE OR TOXICITY: REAL-LIFE DATA FROM A POPULATION-BASED REGISTRY OF BCR-ABL1+CML PATIENTS

Author

Castagnetti, F., Stagno, F., de Vivo, A., Spitalieri, A., Gugliotta, G., Fabbiano, F., Capodanno, I., Mannina, D., Salvucci, M., Antolino, A., Marasca, R., Musso, M., Crugnola, M., Consoli, U., Trabacchi, E., Musolino, C., Cavazzini, Francesco, Longo, G., Tosi, P., Cardinale, G., Soverini, S., Rizzo, M., Martinelli, G., Cavo, M., Vigneri, P., Rosti, G., Di Raimondo, F., and Baccarani, M.

Subjects
Socio-culturale
Published
2016

38. THE EUTOS LONG-TERM SURVIVAL SCORE IS PREDICTIVE FOR RESPONSE AND OUTCOME IN CML PATIENTS TREATED FRONTLINE WITH NILOTINIB-BASED REGIMENS

Author

Castagnetti, F., Gugliotta, G., Breccia, M., Stagno, F., D’Adda, M., Levato, L., Carella, Am, Martino, B., Tiribelli, M., Fava, C., Binotto, G., Avanzini, P., Bocchia, M., Bergamaschi, M., Russo Rossi, A., Cavazzini, Francesco, Abruzzese, E., Soverini, S., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Baccarani, M., and Rosti, G.

Subjects
Socio-culturale
Published
2016

39. High frequency of small insertions and deletions in the BCR-ABL Kinase Domain revealed by ultra-deep sequencing

Author

De Benedittis C, Soverini S, Machova Polakova K, Brouckova A, Castagnetti F, Gugliotta G, Palandri F, Papayannidis C, Klamova H, Bresciani P, Coluccio V, Salvucci M, Tiribelli M, Binotto G, Intermesoli T, Iacobucci I, Venturi C, Luppi M, Ottaviani E, Bochicchio MT, Cattina F, Mancini M, Leo E, Haferlach T, Kohlmann A, Russo D, Rosti G, Baccarani M, Cavo M, Martinelli G, and De Benedittis C, Soverini S, Machova Polakova K, Brouckova A, Castagnetti F,Gugliotta G, Palandri F, Papayannidis C, Klamova H, Bresciani P, Coluccio V, Salvucci M, Tiribelli M, Binotto G, Intermesoli T, Iacobucci I, Venturi C, Luppi M, Ottaviani E, Bochicchio MT, Cattina F, Mancini M, Leo E, Haferlach T, Kohlmann A, Russo D, Rosti G, Baccarani M, Cavo M, Martinelli G

Subjects
Philadelphia-positive Leukemia, 35-base insertion, Bcr-Abl kinase domain mutation, 35INS, deletion, deep-amplicon sequencing, resistance to tyrosine kinase inhibitor, insertion
Published
2013

40. VERY ELDERLY CP-CML PATIENTS TREATED WITH IMATINIB FRONTLINE: HAVE CONCOMITANT THERAPIES AN IMPACT ON OUTCOME AND TOXICITY?

Author

Iurlo, A, Latagliata, R, Bucelli, C, Ferrero, Dario, Castagnetti, F, Breccia, M, Abruzzese, E, Fava, Carmen, Annunziata, M, Stagno, F, Vigneri, P, Tiribelli, M, Cavazzini, F, Binotto, G, Mansueto, G, Gozzini, A, Russo, S, Falzetti, F, Montefusco, E, Gugliotta, G, Cattaneo, D, Djade, Cd, Cedrone, M, Rossi, Ar, Avanzini, P, Pregno, P, Mauro, E, Endri, M, Spadea, A, Celesti, F, Giglio, G, Isidori, A, Crugnola, M, Calistri, E, Sora, F, Sica, S, Storti, S, D'Addosio, A, Rege Cambrin, G, Luciano, L, Saglio, Giuseppe, Rosti, G, Alimena, G, Nobili, A, and Cortelezzi, A.

Published
2015

41. LONG-TERM OUTCOME OF ALTERNATING NILOTINIB 400 MG TWICE DAILY AND IMATINIB 400 MG ONCE DAILY AS FRONTLINE TREATMENT OF CHRONIC MYELOID LEUKEMIA: A PHASE 2 STUDY OF THE GIMEMA CML WORKING PARTY

Author

Gugliotta, G., Castagnetti, F., Breccia, M., Gozzini, A., Stagno, F., Rege Cambrin, G., Carella, A. M., Luciano, L., Abruzzese, E., Martino, B., Usala, E., Rossi, G., Bocchia, M., Cavazzini, Francesco, Tiribelli, M., Luatti, S., Venturi, C., Soverini, S., Cavo, M., Specchia, G., Alimena, G., Pane, F., Martinelli, G., Saglio, G., Rosti, G., and Baccarani, M.

Subjects
Socio-culturale
Published
2015

42. CARDIOVASCULAR EVENTS IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH NILOTINIB FIRST-LINE: AN ANALISYS OF THE GIMEMA CML WP

Author

Gugliotta, G, Castagnetti, F, Breccia, M, Stagno, F, Martino, B, Fava, Carmen, Luciano, L, Gozzini, A, Carella, Am, Abruzzese, E, Levato, L, Usala, E, Rossi, G, Bocchia, M, Tiribelli, M, Cavazzini, F, Salvucci, M, Cedrone, M, Trabacchi, E, Binotto, G, Venturi, C, Soverini, S, Cavo, M, Specchia, G, Alimena, G, Pane, F, Martinelli, G, Saglio, Giuseppe, Baccarani, M, and Rosti, G.

Subjects
Socio-culturale
Published
2015

44. Clinical and biological features in patients with Ph-negative chronic myeloproliferative neoplasms showing different molecular pattern comparative study in 596 patients of the Registro Italiano Trombocitemie (RIT)

Author

Gugliotta, L, Iurlo, A, Gugliotta, G, Tieghi, A, Specchia, G, Gaidano, G, Candoni, A, Randi, Ml, Scalzulli, Pr, Dragani, A, Martinelli, V, Tagariello, G, Antonioli, E, Liberati, Am, Palmieri, R, Langella, M, Rago, A, Cacciola, Rossella Rosaria, Pierri, I, Ricco, A, Cattaneo, D, Santoro, U, Rupoli, S, Santoro, C, Mastrullo, L, Mazzucconi, Mg, Vianelli, N, De Stefano, V, Passamonti, F, and Vannucchi, Am

Published
2015

45. A CRITICAL COMPARISON OF SOKAL, EURO, AND EUTOS RISK SCORES IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH TYROSINE KINASE INHIBITORS

Author

Baccarani, M., Castagnetti, F., Gugliotta, G., Breccia, M., Iurlo, A., Levato, L., Abruzzese, A., Stagno, F., Massimiliano BONIFACIO, Gozzini, A., Pregno, P., Binotto, G., Annunziata, M., Galieni, P., Fava, C., Bocchia, M., Gobbi, M., Russo, D., Specchia, G., Soverini, S., Alimena, G., Martinelli, G., Pane, F., Saglio, G., and Rosti, G.

Subjects
Chronic Myeloid Leukemia, prognosis, TKI treatment, Chronic Myeloid Leukemia, TKI treatment, prognosis
Published
2015

46. VERY ELDERLY CP-CML PATIENTS TREATED WITH IMATINIB FRONTLINE: HAVE CONCOMITANT THERAPIES AN IMPACT ON OUTCOME AND TOXICITY?

Author

Iurlo, A., Latagliata, R., Bucelli, C., Ferrero, D., Castagnetti, F., Breccia, M., Abruzzese, E., Annunziata, C. Fava M., Stagno, F., Vigneri, P., Tiribelli, M., Cavazzini, Francesco, Binotto, G., Mansueto, G., Gozzini, A., Russo, S., Falzetti, F., Montefusco, E., Gugliotta, G., Cattaneo, D., Djade, C. D., Cedrone, M., Russo Rossi, A., Avanzini, P., Pregno, P., Mauro, E., Endri, M., Spadea, A., Celesti, F., Giglio, G., Isidori, A., Crugnola, M., Calistri, E., Sorà, F., Sica, S., Storti, S., D’Addosio, A., Rege Cambrin, G., Luciano, L., Saglio, G., Rosti, G., Alimena, G., Nobili, A., and Cortelezzi, A.

Subjects
Socio-culturale
Published
2015

47. HOW DIAGNOSTIC AND THERAPEUTIC APPROACHE CHANGED IN THE LAST DECADES IN THE PHILADELPHIA NEGATIVE MPN PATIENTS OF THE REGISTRO ITALIANO TROMBOCITEMIE (RIT)

Author

Gugliotta, L., Iurio, A., Gugliotta, G., Alessia Tieghi, Candoni, A., Lunghi, M., Dragani, A., Antonioli, E., Scalzulli, P. R., Martinelli, V., Martino, B., Randi, M. L., Ricco, A., Appolloni, V., Maschio, N., Palmieri, R., Langella, M., Santoro, C., Rago, A., Ragionieri, R., Codeluppi, K., Cacciola, E., Cacciola, R., Mastrullo, L., Esposito, M. R., Caocci, G., Lanza, F., Rupoli, S., Pierri, I., Porretto, F., Melpignano, A., Crugnola, M., Di Ianni, M., Plebani, S., Molinari, E., Spinosa, G., Santoro, M., Villani, O., Ricciotti, M., Musolino, C., Usala, E., Falzetti, F., Biasi, E., Santoro, U., Federici, A., Vianelli, N., Mazzucconi, M. G., and Specchia, G.

Published
2015

48. Additional chromosomal abnormalities in Ph positive clone: adverse prognostic influence on frontline imatinib therapy, a GIMEMA WP on CML analysis

Author

Luatti S, Castagnetti F, Marzocchi G, Baldazzi C, Gugliotta G, Iacobucci I, Specchia G, Zanatta L, Rege Cambrin G, Mancini M, Abruzzese E, Zaccaria A, Grimoldi MG, Gozzetti A, Ameli G, Capucci MA, Palka G, Bernasconi P, Palandri F, Saglio G, Martinelli G, Rosti G, Baccarani M, Testoni N., PANE, FABRIZIO, Luatti, S, Castagnetti, F, Marzocchi, G, Baldazzi, C, Gugliotta, G, Iacobucci, I, Specchia, G, Zanatta, L, Rege Cambrin, G, Mancini, M, Abruzzese, E, Zaccaria, A, Grimoldi, Mg, Gozzetti, A, Ameli, G, Capucci, Ma, Palka, G, Bernasconi, P, Palandri, F, Pane, Fabrizio, Saglio, G, Martinelli, G, Rosti, G, Baccarani, M, and Testoni, N.

Published
2012

49. Ultra-Deep Amplicon Sequencing Using Roche 454 Technology Allows High Sensitivity Bcr-Abl Kinase Domain Mutation Screening and Anticipates Emerging Mutations Leading to Resistance to Tyrosine Kinase Inhibitors in Philadelphia-Positive Leukemia Patients

Author

Soverini S, De Benedittis C, Gnani A, Iacobucci I, Russo D, Cattina F, Castagnetti F, Gugliotta G, Papayannidis C, Vitale A, Elia L, Foà R, Palandri F, Bochicchio MT, Durante S, Rosti G, Baccarani M, Martinelli G., LONETTI, ANNALISA, Soverini S, De Benedittis C, Gnani A, Iacobucci I, Russo D, Cattina F, Castagnetti F, Gugliotta G, Papayannidis C, Vitale A, Elia L, Foà R, Palandri F, Lonetti A, Bochicchio MT, Durante S, Rosti G, Baccarani M, and Martinelli G

Subjects
Leukemia, hemic and lymphatic diseases, Deep Sequencing
Abstract

Definite spectra of point mutations in the Bcr-Abl kinase domain (KD) are known to confer resistance to the tyrosine kinase inhibitors (TKIs) imatinib (IM), dasatinib (DAS) and nilotinib (NIL) in Philadelphia-positive (Ph+) leukemias. Until the recent advent of next-generation sequencing (NGS) technologies, no method was available that could conjugate high sensitivity, possibility to screen for any known or unknown sequence variation and accurate quantitation of mutated subclones. Because of these key technical limitations, the clinical relevance of early detection of small mutated subclones could never be fully elucidated. We have set up and optimized a Bcr-Abl KD mutation screening assay taking advantage of the Roche 454 NGS technology on a GS Junior instrument, that allows parallel pyrosequencing of a hundred thousand clonally amplified DNA molecules of 400 bp average length. We have thus designed 4 partially overlapping amplicons covering the whole KD of the Bcr-Abl transcript (a.a. 240–520) to be generated by nested RT-PCR using sequence-specific primers conjugated with multiplex identifiers – allowing to pool and sequence different samples from one or multiple patients (pts) in a single run. The assay proved capable to identify, characterize and quantitate sequence variations in samples from pts already known to harbour mutations as assessed by conventional Sanger sequencing with 100% concordance. Given that the number of sequence reads generated in each run is relatively constant, the lower detection limit is inversely correlated with the number of samples that can simultaneously be analyzed. Sensitivity could thus be easily modulated – analyzing a single sample per run allowed to routinely achieve lower detection limits ranging between 0.02 and 0.05% (that is, to detect as little as 2 to 5 mutated Bcr-Abl transcripts in a total of 10,000 Bcr-Abl transcripts). With this target sensitivity, we first retrospectively analyzed samples collected at the time of diagnosis from selected chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) cases known to have developed a T315I mutation 3 to 9 months after TKI start. We found that the T315I could not always be traced back to the time of diagnosis. We also found that, both in CML and in Ph+ ALL pts, several low-level mutations (in the range of 0.05 to 1%) with apparently no clinical relevance (e.g., never reported in association with TKI resistance) were routinely detectable – and appeared not to be predictors of a higher level of genetic instability. More interestingly, when used for mutation monitoring of de novo Ph+ ALL pts enrolled in clinical trials with DAS or NIL, NGS could highlight emerging resistant clones far earlier than D-HPLC or conventional sequencing. Also, some IM-resistant CML and Ph+ ALL pts who had been scored as unmutated by conventional sequencing could be shown by NGS to harbour DAS- or NIL-resistant mutations at 1–10% level – a phenomenon that is known to happen because of the clonal deselection resulting from the temporary lack of any TKI selective pressure in the interval between IM discontinuation and DAS or NIL start. Analyses will be presented in detail. We can conclude that: 1) the 454 NGS technology on the GS Junior instrument is a reliable and cost-effective method to perform Bcr-Abl KD mutation screening of Ph+ leukemia pts – with a target sensitivity of 0,1%, 4 samples can simultaneously be analyzed with costs comparable to those of conventional Sanger sequencing and the advantage to quantitatively follow the dynamics of mutated subclones over time; 2) in line with a recent report, small mutated subclones with apparently no clinical relevance can be detected both in newly diagnosed CML and Ph+ ALL pts before TKI start – which further underlines that mutation screening of pts at diagnosis is uninformative, if not misleading; 3) during TKI therapy, the high sensitivity of NGS allows to detect emerging Bcr-Abl mutant subclones earlier than D-HPLC or conventional sequencing; this is particularly relevant: i) for mutation monitoring of Ph+ ALL pts, that are highly prone to develop resistance and mutations while on TKI therapy, and ii) in IM-resistant CML and Ph+ ALL pts, where NGS may uncover the presence of DAS- or NIL-insensitive mutations, and may thus help choosing the second-line therapeutic strategy most likely to be successful.

Published
2011

50. The 'gray zone' of the Ph-negative myeloproliferative neoplasm; proposal of a decision tree useful in the differential diagnosis

Author

Gianelli, U, Ascani, S, Bonoldi, E, Bossi, A, Boveri, E, Cortinovis, I, Moro, A, Fraternali Orcioni, G, Sabattini, E, Valli R, Gugliotta, G, FLORENA, Ada Maria, FRANCO, Vito, Gianelli, U, Ascani, S, Bonoldi, E, Bossi, A, Boveri, E, Cortinovis, I, Florena, AM, Moro, A, Fraternali Orcioni, G, Sabattini, E, Valli R, Gugliotta, G, and Franco, V

Subjects
ph-negative MPN, bone marrow biopsy, Settore MED/08 - Anatomia Patologica
Published
2010

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