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1. 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
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2. 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
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3. Reply to: Second primary malignancies in myeloproliferative neoplasms and the role of aspirin

Author: Barbui, T., Ghirardi, A., Vannucchi, A. M., Marchetti, M., De Stefano, Valerio, Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Bertolotti, L., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Griesshammer, M., Alvarez-Larran, A., and Rambaldi, A.
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Aspirin, business.industry, Hematology, Second primary cancer, Settore MED/15 - MALATTIE DEL SANGUE, Internal medicine, medicine, business, Myelopriferative neoplasms, medicine.drug
Published: 2019
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4. 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

5. Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib

Author: Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., on behalf of the GIMEMA CML Working Party (Lucarelli, G., Polimeno, G., Ladetto, M., Pini, M., Rupoli, S., Scortechini, A. R., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Specchia, G., Russo, Rossi., Rambaldi, A., Ferrari, M. L., Palandri, F., Luatti, S., Iacobucci, I., Bochicchio, M. T., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Giuliani, G., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Molica, S., Lentini, M., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cuneo, A., Ciccone, M., Bosi, A., Gozzini, A., Gobbi, M., Pierri, I., Chianese, R., De Blasio, A., Ciccone, F., Capochiani, E., Pelosini, M., Musolino, C., Russo, S., Cortelezzi, A., Luppi, M., Marasca, R., Pogliani, E. M., Gambacorti-Passerini, C., Luciano, L., Izzo, B., Ferrara, F., Annunziata, M., Mettivier, V., Sessa, U., 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., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidor, I., Di Bartolomeo, P., Di Lorenzo, R., Vallisa, D., Trabacch, I., Pizzuti, M., Zuffa, E., Salvucci, M., Ronco, F., Lelo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Sica, S., Sorà, F., Latagliata, R., De Fabritiis, P., Trawiska, M., Amadori, S., Cantonetti, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Mengarelli, A., Romano, A., Tafuri, A., Montefusc, O., Iuliano, F., Infusino, S., Dore, F., Fozza, C., Bocchia, M., Defina, M., Liberati, Am., Luzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Nicolosi, M., Gottardi, M., Calistri, E., Fanin, R., Tiribelli, M., Pizzolo, G., Bonifacio, M., Rodeghiero, F., Di Bona, E. )., Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., and on behalf of the GIMEMA CML Working Party [, Palandri F.], Pane, Fabrizio, Gugliotta, G, Breccia, M, Stagno, F, Iurlo, A, Albano, F, Abruzzese, E, Martino, B, Levato, L, Intermesoli, T, Pregno, P, Rossi, G, Gherlinzoni, F, Leoni, P, Cavazzini, F, Venturi, C, Soverini, S, Testoni, N, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Baccarani, M, and GAMBACORTI PASSERINI, C
Subjects: DIAGNOSED CHRONIC-PHASE, Oncology, Male, Cancer Research, Time Factors, bcr-abl, Fusion Proteins, bcr-abl, Antineoplastic Agent, Hematology, Anesthesiology and Pain Medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Cumulative incidence, Young adult, Chronic, Aged, 80 and over, Leukemia, PATIENTS RECEIVING IMATINIB, CHRONIC MYELOGENOUS LEUKEMIA, TYROSINE KINASE INHIBITORS, BCR-ABL1 TRANSCRIPT LEVELS, EARLY MOLECULAR RESPONSE, CML WORKING PARTY, 3-YEAR FOLLOW-UP, EUROPEAN LEUKEMIANET, 400 MG, Myeloid leukemia, Middle Aged, Prognosis, Treatment Outcome, Retreatment, Imatinib Mesylate, Female, Tyrosine kinase, Human, medicine.drug, Adult, medicine.medical_specialty, Time Factor, Adolescent, Prognosi, Protein Kinase Inhibitor, Socio-culturale, Antineoplastic Agents, Treatment results, Follow-Up Studie, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, Protein Kinase Inhibitors, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Fusion Proteins, Imatinib, Follow-Up Studies, Surgery, Imatinib mesylate, BCR-ABL Positive, business, Myelogenous
Abstract: For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.
Published: 2015

6. Hormone replacement therapy reduced 24-hour blood pressure in postmenopausal hypertensive women

Author: Affinito, P., Palomba, S., Bonifacio, M., Fontana, D., Izzo, R., Trimarco, B., Nappi, C., Shlipak, M. G., Affinito, P., Palomba, S., Bonifacio, M., Fontana, D., Izzo, R., Trimarco, B., Nappi, C., and Shlipak, M. G.
Subjects: medicine.medical_specialty, Blood pressure, business.industry, Urology, medicine, Obstetrics and Gynecology, Hormone replacement therapy, business
Published: 2002
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7. Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial

Author: Alberto Ferrari, Cristina Bucelli, Elisa Rumi, Barbara Mora, Alessandra Carobbio, Fabrizio Pane, Tiziano Barbui, Gianni Tognoni, Andrea Patriarca, Francesca Palandri, Giuseppe Carli, Nicola Cascavilla, Elena Rossi, Sergio Siragusa, Alessandra Iurlo, Giuseppe Gaetano Loscocco, Fabio Ciceri, Maria Chiara Finazzi, Alessandro M. Vannucchi, Davide Rapezzi, Carmela Mannarelli, Giulia Benevolo, Arianna Masciulli, Marianna Caramella, Luigi Scaffidi, Arianna Ghirardi, Nicola Vianelli, Silvia Betti, Massimiliano Bonifacio, Alessandro Rambaldi, Valerio De Stefano, Marta Bellini, Paola Guglielmelli, Francesca Lunghi, Emma Cacciola, Alessandra Ricco, Caterina Musolino, Barbui T., Vannucchi A.M., De Stefano V., Masciulli A., Carobbio A., Ferrari A., Ghirardi A., Rossi E., Ciceri F., Bonifacio M., Iurlo A., Palandri F., Benevolo G., Pane F., Ricco A., Carli G., Caramella M., Rapezzi D., Musolino C., Siragusa S., Rumi E., Patriarca A., Cascavilla N., Mora B., Cacciola E., Mannarelli C., Loscocco G.G., Guglielmelli P., Betti S., Lunghi F., Scaffidi L., Bucelli C., Vianelli N., Bellini M., Finazzi M.C., Tognoni G., Rambaldi A., Barbui, T., Vannucchi, A. M., De Stefano, V., Masciulli, A., Carobbio, A., Ferrari, A., Ghirardi, A., Rossi, E., Ciceri, F., Bonifacio, M., Iurlo, A., Palandri, F., Benevolo, G., Pane, F., Ricco, A., Carli, G., Caramella, M., Rapezzi, D., Musolino, C., Siragusa, S., Rumi, E., Patriarca, A., Cascavilla, N., Mora, B., Cacciola, E., Mannarelli, C., Loscocco, G. G., Guglielmelli, P., Betti, S., Lunghi, F., Scaffidi, L., Bucelli, C., Vianelli, N., Bellini, M., Finazzi, M. C., Tognoni, G., and Rambaldi, A.
Subjects: Adult, Male, medicine.medical_specialty, Polycythaemia, Neutropenia, Adolescent, Policithemia vera, Interferon alpha-2, Polymorphism, Single Nucleotide, law.invention, Polyethylene Glycols, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Randomized controlled trial, Phlebotomy, law, Bone Marrow, Internal medicine, medicine, Clinical endpoint, Data monitoring committee, Humans, Polycythemia Vera, business.industry, Standard treatment, Interferon-alpha, Hematology, Janus Kinase 2, Middle Aged, Interim analysis, medicine.disease, Recombinant Proteins, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, Quality of Life, Female, business, 030215 immunology
Abstract: Summary Background There is no evidence that phlebotomy alone is sufficient to steadily maintain haematocrit on target level in low-risk patients with polycythaemia vera. This study aimed to compare the efficacy and safety of ropeginterferon alfa-2b on top of the standard phlebotomy regimen with phlebotomy alone. Methods In 2017, we launched the Low-PV study, a multicentre, open-label, two-arm, parallel-group, investigator-initiated, phase 2 randomised trial with a group-sequential adaptive design. The study involved 21 haematological centres across Italy. Participants were recruited in a consecutive order. Participants enrolled in the study were patients, aged 18–60 years, with a diagnosis of polycythaemia vera according to 2008–16 WHO criteria. Eligible patients were randomly allocated (1:1) to receive either phlebotomy and low-dose aspirin (standard group) or ropeginterferon alfa-2b on top of the standard treatment (experimental group). Randomisation sequence was generated using five blocks of variable sizes proportional to elements of Pascal's triangle. Allocation was stratified by age and time from diagnosis. No masking was done. Patients randomly allocated to the standard group were treated with phlebotomy (300 mL for each phlebotomy to maintain the haematocrit values of lower than 45%) and low-dose aspirin (100 mg daily), if not contraindicated. Patients randomly allocated to the experimental group received ropeginterferon alfa-2b subcutaneously every 2 weeks in a fixed dose of 100 μg on top of the phlebotomy-only regimen. The primary endpoint was treatment response, defined as maintenance of the median haematocrit values of 45% or lower without progressive disease during a 12-month period. Analyses were done by intention-to-treat principle. The study was powered assuming a higher percentage of responders in the experimental group (75%) than in the standard group (50%). Here we report results from the second planned interim analysis when 50 patients had been recruited to each group. The trial is ongoing, and registered with ClinicalTrials.gov , NCT03003325 . Findings Between Feb 2, 2017, and March 13, 2020, 146 patients were screened, and 127 patients were randomly assigned to the standard group (n=63) or the experimental group (n=64). The median follow-up period was 12·1 months (IQR 12·0–12·6). For the second pre-planned interim analysis, a higher response rate in the experimental group was seen (42 [84%] of 50 patients) than in the standard group (30 [60%] of 50 patients; absolute difference 24%, 95% CI 7–41%, p=0·0075). The observed z value (2·6001) crossed the critical bound of efficacy (2·5262), and the stagewise adjusted p value early showed superiority of experimental treatment. Thus, the data safety monitoring board decided to stop patient accrual for overwhelming efficacy and to continue the follow-up, as per protocol, for 2 years. Under the safety profile, no statistically significant difference between groups in frequency of adverse events of grade 3 or higher was observed; the most frequently reported adverse events were neutropenia (four [8%] of 50 patients) in the experimental group and skin symptoms (two [4%] of 50 patients) in the standard group. No grade 4 or 5 adverse events occurred. Interpretation Supplementing phlebotomy with ropeginterferon alfa-2b seems to be safe and effective in steadily maintaining haematocrit values on target in low-risk patients with polycythaemia vera. Findings from the current study might have implications for changing the current management of low-risk patients with polycythaemia vera. Funding AOP Orphan Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro
Published: 2020

8. Managing chronic myeloid leukemia for treatment-free remission: A proposal from the GIMEMA CML WP

Author: Francesca Lunghi, Gabriele Gugliotta, Chiara Elena, Valentina Giai, Monica Bocchia, Marco Cerrano, Monia Lunghi, Gaetano La Barba, Fausto Castagnetti, Germana Beltrami, Simona Soverini, Paola Fazi, Micaela Bergamaschi, Sara Galimberti, Mario Tiribelli, Claudio Fozza, Antonella Gozzini, Fabrizio Pane, Elena Trabacchi, Massimo Breccia, Mario Annunziata, Isabella Capodanno, Domenico Russo, Serena Rupoli, Sara Barulli, Giovanna Rege-Cambrin, Michele Baccarani, Gianni Binotto, Fausto Palmieri, Roberto Marasca, Bruno Martino, Alessandro Lucchesi, E Abruzzese, Paolo Vigneri, Carmen Fava, Alessandra Iurlo, Francesco Albano, Caterina Musolino, Michele Cedrone, Luigia Luciano, Fabio Stagno, Gianantonio Rosti, Patrizia Pregno, Rosaria Sancetta, Angela Melpignano, Raffaele Spadano, Massimiliano Bonifacio, Luciano Levato, Marzia Salvucci, Vincenzo Accurso, Monica Crugnola, Michele Malagola, Davide Rapezzi, Giovanni Caocci, Mariella D'Adda, Simona Sica, Giuseppe Saglio, Maria Cristina Miggiano, Enrico Montefusco, Simona Tomassetti, Francesco Cavazzini, Baccarani, M., Abruzzese, E., Accurso, V., Albano, F., Annunziata, M., Barulli, S., Beltrami, G., Bergamaschi, M., Binotto, G., Bocchia, M., Caocci, G., Capodanno, I., Cavazzini, F., Cedrone, M., Cerrano, M., Crugnola, M., D'Adda, M., Elena, C., Fava, C., Fazi, P., Fozza, C., Galimberti, S., Giai, V., Gozzini, A., Gugliotta, G., Iurlo, A., la Barba, G., Levato, L., Lucchesi, A., Luciano, L., Lunghi, F., Lunghi, M., Malagola, M., Marasca, R., Martino, B., Melpignano, A., Miggiano, M. C., Montefusco, E., Musolino, C., Palmieri, F., Pregno, P., Rapezzi, D., Rege-Cambrin, G., Rupoli, S., Salvucci, M., Sancetta, R., Sica, S., Spadano, R., Stagno, F., Tiribelli, M., Tomassetti, S., Trabacchi, E., Bonifacio, M., Breccia, M., Castagnetti, F., Pane, F., Russo, D., Saglio, G., Soverini, S., Vigneri, P., Rosti, G., Baccarani M., Abruzzese E., Accurso V., Albano F., Annunziata M., Barulli S., Beltrami G., Bergamaschi M., Binotto G., Bocchia M., Caocci G., Capodanno I., Cavazzini F., Cedrone M., Cerrano M., Crugnola M., D'Adda M., Elena C., Fava C., Fazi P., Fozza C., Galimberti S., Giai V., Gozzini A., Gugliotta G., Iurlo A., la Barba G., Levato L., Lucchesi A., Luciano L., Lunghi F., Lunghi M., Malagola M., Marasca R., Martino B., Melpignano A., Miggiano M.C., Montefusco E., Musolino C., Palmieri F., Pregno P., Rapezzi D., Rege-Cambrin G., Rupoli S., Salvucci M., Sancetta R., Sica S., Spadano R., Stagno F., Tiribelli M., Tomassetti S., Trabacchi E., Bonifacio M., Breccia M., Castagnetti F., Pane F., Russo D., Saglio G., Soverini S., Vigneri P., and Rosti G.
Subjects: Male, Pediatrics, Fusion Proteins, bcr-abl, Chronic myelogenous leukemia, tyrosine kinase inhibitors, additional chromosomal-abnormalities, deep molecular responses, high-dose imatinib, randomized cml, domain mutations, prognostic-significance, cytogenetic response, frontline nilotinib, Pregnancy, chronic myeloid leukemia,management,recommendations,Gimema,treatment-free remission, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Young adult, Disease management (health), Myeloid Neoplasia, Remission Induction, Myeloid leukemia, Disease Management, Hematology, Health Care Costs, Middle Aged, Leukemia, Treatment Outcome, Italy, Retreatment, Treatment strategy, Female, management, Human, Adult, medicine.medical_specialty, Adolescent, Chronic Myeloid Leukemia, Protein Kinase Inhibitor, Socio-culturale, Treatment-Free Remission, Gimema, Myelogenous, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Long term survival, Humans, Protein Kinase Inhibitors, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, Health Care Cost, Settore MED/15 - MALATTIE DEL SANGUE, treatment in chronic phase chronic myeloid leukemia, Health Care Survey, Health Care Surveys, recommendations, Disease risk, business
Abstract: Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.
Published: 2019

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

Author: D. Ielo, Mario Cazzola, A. De Vivo, Mario Petrini, G. Fioritoni, Simona Sica, Fausto Castagnetti, B. Falini, Miriam Fogli, Agostino Cortelezzi, C. Viganò, Giuliana Alimena, Maurizio Musso, G. Spinosa, Flavia Salvi, Giancarlo Latte, Michele Pizzuti, Nicola Cantore, D. Luzzi, B. Ronci, Francesco Merli, Mario Boccadoro, Diamante Turri, Monica Bocchia, Patrizia Tosi, A. M. Carella, Simona Luatti, G. Semenzato, Mariella Grasso, Nicoletta Testoni, Giovanni Martinelli, Ester Pungolino, Giuseppe Tagariello, A. Russo Rossi, Simona Soverini, Francesca Ronco, Franco Iuliano, Giovanni Rosti, Alberto Bosi, Tamara Intermesoli, Dario Ferrero, Sara Galimberti, Giovanna Rege-Cambrin, Ferdinando Porretto, Sabina Russo, Roberto Latagliata, Pellegrino Musto, E. Morra, Agostino Tafuri, Franca Falzetti, Francesco Cavazzini, P. Galieni, Marzia Salvucci, F. Rodighiero, Stefana Impera, Fausto Dore, P. De Fabritiis, V. Meneghini, Elisabetta Calistri, Paolo Vigneri, Ivana Pierri, Michele Cavo, Massimo Pini, Fabrizio Ciccone, Domenico Russo, E Trabacchi, Franco Gherlinzoni, Michele Baccarani, Ilaria Iacobucci, Roberto Sartori, Paolo Avanzini, D. Noli, Roberto Marasca, Simonetta Pardini, A. Malpignano, Maria Concetta Petti, Bruno Martino, M. Bergamaschi, Giovanni Pizzolo, Valeria Santini, E Orlandi, Catia Bigazzi, Serena Rupoli, Giuseppe Saglio, I. Cervello, Clementina Caracciolo, Anna Merli, R. Di Lorenzo, Enrico Pogliani, Francesco Lanza, Mariella Girasoli, M. Apolinari, Caterina Musolino, Francesco Fabbiano, D. Vallisa, Mario Annunziata, Gabriele Gugliotta, V. De Stefano, Ignazio Majolino, Sergio Storti, P. Leoni, Adele Capucci, Massimo Breccia, Alessandro Isidori, Carmen Fava, Gianni Binotto, Carlo Gambacorti-Passerini, L. Pacilli, Mario Tiribelli, Luciano Levato, Felicetto Ferrara, N. Di Renzo, Anna D'Emilio, Francesco Pisani, Fabio Stagno, Monica Crugnola, M. Trawiska, Patrizia Pregno, Marzia Defina, Stefano Molica, Mario Luppi, Michele Malagola, Davide Rapezzi, A. M. Liberati, E. De Biasi, A. Iurlo, Umberto Vitolo, Silvana Capalbo, Maria Teresa Bochicchio, F. Di Raimondo, Franco Aversa, Giuseppe Visani, Fausto Palmieri, Alessandro Rambaldi, Sergio Siragusa, Massimiliano Bonifacio, Luigiana Luciano, Giorgina Specchia, Elisabetta Abruzzese, A. De Blasio, Francesco Albano, Antonio Cuneo, Emilio Usala, Alfonso Zaccaria, R Fanin, Francesca Palandri, Fabrizio Pane, Enrico Montefusco, A. Gozzini, Giulio Rossi, Emanuele Angelucci, A. Bacigalupo, Marco Gobbi, Michele Cedrone, 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., on behalf of the, GIMEMA CML Working Party [.., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, M.T., Apolinari, M., Fogli, M., Cervello, I., ]., Castagnetti, Fausto, De Vivo, A., Pane, Fabrizio, 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., Bochicchio, M. T., 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, 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, M, 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, Spinosa, G, Pierri, I, Bergamaschi, M, Carella, A, Bacigalupo, A, De Blasio, A, Ciccone, F, Di Renzo, N, Musolino, C, Russo, S, Cortelezzi, A, Morra, E, Pungolino, E, Luppi, M, Marasca, R, Pogliani, E, 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, Pisani, F, Tafuri, A, Montefusco, E, Iuliano, F, Dore, F, Pardini, S, Bocchia, M, Defina, M, Liberati, A, Luzzi, D, Boccadoro, M, Ferrero, D, Vitolo, U, Gherlinzoni, F, Calistri, E, Fanin, R, Pizzolo, G, Meneghini, V, Rodighiero, F, and D'Emilio, A
Subjects: Male, Pediatrics, Host response, BCR-ABL, Chronic myeloid leukemia, Prognosis, Tyrosine kinase inhibitors, Young adults, Adult, Age Factors, Aged, Aged, 80 and over, Antineoplastic Agents, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Middle Aged, Prospective Studies, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Spleen, Splenomegaly, Young Adult, Oncology, Hematology, Tyrosine kinase inhibitor, Disease, Antineoplastic Agent, Tyrosin kinase inhibitor, Protein-Tyrosine Kinase, hemic and lymphatic diseases, 80 and over, Age Factor, Young adult, Chronic, Leukemia, Incidence (epidemiology), Myeloid leukemia, bcr-abl1, chronic myeloid leukemia, prognosis, tyrosine kinase inhibitors, young adults, Human, medicine.medical_specialty, Prognosi, Protein Kinase Inhibitor, NO, medicine, Adult patients, business.industry, medicine.disease, Clinical trial, Prospective Studie, Medicine (all), Immunology, BCR-ABL Positive, BCR-ABL, chronic myeloid leukemia, prognosis, tyrosine kinase inhibitors, young adults, business, Myelogenous
Abstract: BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Published: 2015

10. Drug resistance and BCR-ABL kinase domain mutations in philadelphia chromosome-positive acute lymphoblastic leukemia from the imatinib to the second-generation tyrosine kinase inhibitor era: The main changes are in the type of mutations, but not in the frequency of mutation involvement

Author: Paola Bresciani, Simona Soverini, Fabrizio Pane, Stefania Paolini, Marzia Salvucci, Tamara Intermesoli, Domenico Russo, Claudia Venturi, Giovanni Martinelli, Simona Sica, Michele Baccarani, Michele Cavo, Ester Orlandi, Cristina Papayannidis, Mario Luppi, Massimiliano Bonifacio, Ilaria Iacobucci, Caterina De Benedittis, Antonella Gozzini, Gian Matteo Rigolin, Soverini, S., De Benedittis, C., Papayannidis, C., Paolini, S., Venturi, C., Iacobucci, I., Luppi, M., Bresciani, P., Salvucci, M., Russo, D., Sica, S., Orlandi, E., Intermesoli, T., Gozzini, A., Bonifacio, M., Rigolin, G.M., Pane, F., Baccarani, M., Cavo, M., Martinelli, G., Soverini, S, De Benedittis, C, Papayannidis, C, Paolini, S, Venturi, C, Iacobucci, I, Luppi, M, Bresciani, P, Salvucci, M, Russo, D, Sica, S, Orlandi, E, Intermesoli, T, Gozzini, A, Bonifacio, M, Rigolin, Gm, Pane, Fabrizio, Baccarani, M, and Cavo, M
Subjects: Male, Cancer Research, TKI inhibitors, DNA Mutational Analysis, Fusion Proteins, bcr-abl, BCR-ABL mutations, acute lymphoblastic leukemia, dasatinib, imatinib, resistance, Adolescent, Adult, Aged, Benzamides, Drug Resistance, Neoplasm, Female, Humans, Middle Aged, Piperazines, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prospective Studies, Protein Kinase Inhibitors, Pyrimidines, Young Adult, Mutation, medicine.disease_cause, Tyrosine-kinase inhibitor, hemic and lymphatic diseases, Mutation frequency, Dasatinib, Oncology, BCR-ABL mutation, Imatinib Mesylate, Tyrosine kinase, medicine.drug, Human, medicine.drug_class, Protein Kinase Inhibitor, Philadelphia chromosome, NO, DNA Mutational Analysi, Benzamide, medicine, Piperazine, business.industry, acute lymphoblastic leukemia, Philadelphia chromosome, TKI inhibitors, Cancer, Imatinib, medicine.disease, Prospective Studie, Settore MED/15 - MALATTIE DEL SANGUE, Imatinib mesylate, Pyrimidine, IMATINIB MESYLATE, Immunology, Cancer research, business
Abstract: BACKGROUND Patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) frequently relapse on imatinib with acquisition of BCR-ABL kinase domain (KD) mutations. To analyze the changes that second-generation tyrosine kinase inhibitors (TKIs) have brought in mutation frequency and type, a database review was undertaken of the results of all the BCR-ABL KD mutation analyses performed in the authors' laboratory from January 2004 to January 2013. METHODS Interrogation of the database retrieved 450 mutation analyses in 272 patients with Ph+ ALL. Prescreening of samples was performed with denaturing high-performance liquid chromatography (D-HPLC), followed by direct sequencing of D-HPLC–positive cases. RESULTS BCR-ABL KD mutations were detected in 70% of imatinib-resistant patients, with T315I, E255K, and Y253H mutations accounting for 75% of cases. Seventy-eight percent of the patients reported to be resistant to second-generation TKIs after imatinib failure were positive for mutations, and 58% of them had multiple mutations. Analysis of patients relapsing on dasatinib revealed a newly acquired T315I mutation in almost two-thirds of the cases. Direct sequencing detected no mutations at diagnosis, even in patients who relapsed after a few months. CONCLUSIONS Second-generation TKIs ensure a more rapid debulking of the leukemic clone and have much fewer insensitive mutations, but long-term disease control remains a problem, and the T315I mutation is revealed to be an even more frequent enemy. BCR-ABL KD mutation screening of patients with Ph+ ALL who are receiving imatinib or second-generation TKIs would be a precious ally for timely treatment optimization. In contrast, the clinical usefulness of conventional direct sequencing at diagnosis seems to be very low. Cancer 2014;120:1002–1009. © 2013 American Cancer Society.
Published: 2014

11. Impact of comorbidities and body mass index on the outcome of polycythemia vera patients

Author: Alessia Tieghi, Alessandra D'Addio, Florian H. Heidel, Roberto Latagliata, Elisa Bossi, Francesco Cavazzini, Giulia Benevolo, Nicola Vianelli, Michele Cavo, Roberto M. Lemoli, Mauro Krampera, Massimo Breccia, Massimiliano Bonifacio, Gianni Binotto, Antonio Cuneo, Giovanni Caocci, Daniela Bartoletti, Mario Tiribelli, Ida Carmosino, Lucia Catani, Giuseppe Auteri, Francesco Lanza, Giuseppe A. Palumbo, Nicola Polverelli, Francesca Palandri, Micaela Bergamaschi, Monica Crugnola, Elena Maria Elli, Benevolo G., Elli E.M., Bartoletti D., Latagliata R., Tiribelli M., Heidel F.H., Cavazzini F., Bonifacio M., Crugnola M., Binotto G., D'Addio A., Tieghi A., Bergamaschi M., Caocci G., Polverelli N., Bossi E., Auteri G., Carmosino I., Catani L., Cuneo A., Krampera M., Lanza F., Lemoli R.M., Vianelli N., Breccia M., Palumbo G.A., Cavo M., and Palandri F.
Subjects: Male, Cancer Research, Comorbidity, Overweight, Primary Myelofibrosi, 0302 clinical medicine, Retrospective Studie, Risk Factors, body mass index, cancer, Charlson comorbidity index, outcome, polycythemia vera, thrombotic risk, 80 and over, Cumulative incidence, Aged, 80 and over, Incidence, Incidence (epidemiology), Hazard ratio, Hematology, General Medicine, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Thrombosi, Female, Underweight, medicine.symptom, Human, Adult, medicine.medical_specialty, NO, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Retrospective Studies, business.industry, Risk Factor, Thrombosis, Retrospective cohort study, medicine.disease, Follow-Up Studies, Polycythemia Vera, Primary Myelofibrosis, Body Mass Index, Body Mass Index, Cancer, Charlson Comorbidity Index, Outcome, Polycythemia Vera, Thrombotic risk, business, Body mass index, 030215 immunology
Abstract: In 816 patients with 2016 World Health Organization-defined polycythemia vera (PV) enrolled in a multicenter retrospective study, we investigated the predictive value of Charlson comorbidity index (CCI) and body mass index (BMI) on thrombosis, progression to post-PV myelofibrosis (PPV-MF) and survival. Patients were subgrouped according to CCI=0 (58.1%, no comorbidities) or CCI≥1 (41.9%) and according to normal/underweight (BMI&nbsp
Published: 2021
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12. BCR-ABL1 compound mutants: prevalence, spectrum and correlation with tyrosine kinase inhibitor resistance in a consecutive series of Philadelphia chromosome-positive leukemia patients analyzed by NGS

Author: Fausto Castagnetti, Simona Sica, Cristina Papayannidis, Antonio Percesepe, Monica Crugnola, Gabriele Gugliotta, Michele Cavo, Mariella D'Adda, Massimiliano Bonifacio, Federica Sorà, Gianantonio Rosti, Michele Baccarani, Caterina De Benedittis, Simona Soverini, Isabella Capodanno, Giovanni Martinelli, Luana Bavaro, Margherita Martelli, Patrizia Pregno, Flavio Mignone, Alessandra Iurlo, Francesca Lunghi, Francesco Albano, Sara Galimberti, Soverini S., Martelli M., Bavaro L., De Benedittis C., Sica S., Sora F., Iurlo A., Bonifacio M., Pregno P., Galimberti S., Lunghi F., Albano F., D'Adda M., Crugnola M., Capodanno I., Castagnetti F., Gugliotta G., Papayannidis C., Rosti G., Percesepe A., Mignone F., Baccarani M., Martinelli G., and Cavo M.
Subjects: Cancer Research, medicine.drug_class, bcr-abl, Mutant, Fusion Proteins, bcr-abl, Drug Resistance, Philadelphia chromosome, Tyrosine-kinase inhibitor, Bcr abl1, Protein-Tyrosine Kinases, Prevalence, medicine, Humans, Philadelphia Chromosome, Protein Kinase Inhibitors, Leukemia, Philadelphia Chromosome Positive, business.industry, High-Throughput Nucleotide Sequencing, Fusion Proteins, Hematology, medicine.disease, Molecular biology, Oncology, Drug Resistance, Neoplasm, Neoplasm, business, BCR-ABL1, tyrosine kinase inhibitor resistance, Philadelphia chromosome-positive leukemia
Abstract: NA
Published: 2020
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13. Validation and reference values of the EORTC QLQ-CML24 questionnaire to assess health-related quality of life in patients with chronic myeloid leukemia

Author: Nicole M. A. Blijlevens, Geneviève I. C. G. Ector, Ping Chong Bee, Federica Sorà, Nicola Di Renzo, Massimiliano Bonifacio, Andrea Patriarca, Maria Cristina Miggiano, Elisabetta Abruzzese, I Capodanno, Giovanni Caocci, Chonghua Wan, Michele Baccarani, Susanne Saussele, Iris Okumura, Fabio Stagno, Simone Oerlemans, Alessandra Iurlo, Francesco Cottone, Francesco Albano, Vamsi Kota, Nicola Cascavilla, Marco Vignetti, Gianantonio Rosti, Fabio Efficace, Fausto Castagnetti, Chiara Elena, Monika Sztankay, Massimo Breccia, Efficace F., Iurlo A., Patriarca A., Stagno F., Bee P.-C., Ector G., Capodanno I., Elena C., Bonifacio M., Blijlevens N.M.A., Caocci G., Wan C., Abruzzese E., Breccia M., Cottone F., Okumura I., Oerlemans S., Cascavilla N., Albano F., Kota V., Sztankay M., Miggiano M.C., Saussele S., Di Renzo N., Sora F., Castagnetti F., Baccarani M., Vignetti M., and Rosti G.
Subjects: Oncology, Cancer Research, medicine.medical_specialty, patient-reported outcome, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Quality of life, Cronbach's alpha, chronic myeloid leukemia, Reference Values, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Surveys and Questionnaires, hemic and lymphatic diseases, Internal medicine, tyrosine kinase inhibitors, medicine, Humans, neoplasms, business.industry, Reproducibility of Results, Myeloid leukemia, Imatinib, Hematology, medicine.disease, symptom, Comorbidity, humanities, Confirmatory factor analysis, Settore MED/15 - MALATTIE DEL SANGUE, Nilotinib, validation and reference values of the EORTC QLQ-CML24 questionnaire, 030220 oncology & carcinogenesis, Quality of Life, business, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], 030215 immunology, medicine.drug
Abstract: Item does not contain fulltext Health-related quality of life (HRQOL) assessment is important to facilitate decisions in the current treatment landscape of chronic myeloid leukemia (CML). Therefore, the availability of a validated HRQOL questionnaire, specifically developed for CML patients treated with tyrosine kinase inhibitors (TKIs), may enhance quality of research in this area. We performed an international study including 782 CML patients to assess the validity of the EORTC QLQ-CML 24 questionnaire, and to generate HRQOL reference values to facilitate interpretation of results in future studies. Internal consistency, assessed with Cronbach's alpha coefficients, ranged from 0.66 to 0.83. In the confirmatory factor analysis, all standardized factor loadings exceeded the threshold of 0.40 (range 0.49-0.97), confirming the hypothesized scale structure. Reference values stratified by age and sex were also generated. Our findings support the use of the EORTC QLQ-CML 24, in conjunction with the EORTC QLQ-C30, as a valuable measure to assess HRQOL in CML patients.
Published: 2020
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14. COVID-19 infection in chronic myeloid leukaemia after oneyear of the pandemic in Italy. A Campus CML report

Author: Elisabetta Abruzzese, Sabina Russo, Carmen Fava, Francesca Lunghi, Sabrina Leonetti Crescenzi, Chiara Elena, Vincenzo Accurso, Fausto Castagnetti, Debora Luzi, Giovanni Caocci, Elena Crisà, Maria Cristina Miggiano, Massimo Breccia, Antonella Gozzini, Giuseppina Loglisci, Giovanna Rege-Cambrin, Monica Bocchia, Immacolata Attolico, Massimiliano Bonifacio, Luigiana Luciano, Gaetano La Barba, Gianantonio Rosti, Maria Stella De Candia, Roberto Latagliata, Gabriele Gugliotta, Francesco Cavazzini, Rosaria Sancetta, Micaela Bergamaschi, Anna Rita Scortechini, Sara Galimberti, Tamara Intermesoli, Federica Sorà, Luciano Levato, Paolo Sportoletti, Monica Crugnola, Mario Tiribelli, Isabella Capodanno, Giuseppe Saglio, Davide Rapezzi, Robin Foà, Alessandra Iurlo, Alessandro Lucchesi, Michele Pizzuti, Sara Barulli, Fabio Stagno, Patrizia Pregno, Alessandra Malato, Gianni Binotto, Agostino Tafuri, 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., Crisa E., Crugnola M., Stella De Candia M., Elena C., Fava C., Galimberti S., Gozzini A., Gugliotta G., Intermesoli T., Iurlo A., La Barba G., Latagliata R., Leonetti Crescenzi S., Levato L., Loglisci G., Lucchesi A., Luciano L., Lunghi F., Luzi D., Malato A., Cristina Miggiano M., Pizzuti M., Pregno P., Rapezzi D., Rege-Cambrin G., Rosti G., Russo S., Sancetta R., Rita Scortechini A., Sora F., Sportoletti P., Stagno F., Tafuri A., Tiribelli M., Foa R., and Saglio G.
Subjects: Male, Tyrosine-kinase inhibitor, law.invention, law, Retrospective Studie, Pandemic, Chronic, Covid‐19, Leukemia, Mortality rate, Hematology, Middle Aged, Intensive care unit, Research Papers, Survival Rate, Italy, covid-19, Hematologic Neoplasms, Cohort, Female, prognosi, Human, Research Paper, chronic myeloid leukemia, Covid-19, prognosis, mortality, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.drug_class, chronic myeloid leukemia, prognosis, mortality, Chronic myeloid leukaemia, Disease-Free Survival, NO, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Covid-19, mortality, prognosis, Aged, Humans, Retrospective Studies, COVID-19, Pandemics, SARS-CoV-2, medicine, business.industry, Concomitant, Commentary, BCR-ABL Positive, business, Myelogenous
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 8665 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 65years 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 18years). 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

15. Health-related quality of life of newly diagnosed chronic myeloid leukemia patients treated with first-line dasatinib versus imatinib therapy

Author: Marco Vignetti, Antonella Gozzini, Andrea Patriarca, Fausto Castagnetti, Massimo Breccia, Alessandra Iurlo, Monica Crugnola, Elisabetta Abruzzese, Bruno Martino, Claudio Fozza, Nicola Cascavilla, Gianni Binotto, Giovanni Caocci, Massimiliano Bonifacio, I Capodanno, Fabio Stagno, Patrizia Pregno, Micaela Bergamaschi, Francesco Cottone, Fabio Efficace, Mario Tiribelli, Gianantonio Rosti, Susanne Saussele, Efficace F., Stagno F., Iurlo A., Breccia M., Cottone F., Bonifacio M., Abruzzese E., Castagnetti F., Caocci G., Crugnola M., Capodanno I., Martino B., Tiribelli M., Patriarca A., Gozzini A., Pregno P., Saussele S., Cascavilla N., Fozza C., Bergamaschi M., Binotto G., Vignetti M., and Rosti G.
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, chronic myeloid leukemia, health-related quality of life, tyrosine kinase inhibitors, EORTC QLQ, Antineoplastic Agents, 03 medical and health sciences, 0302 clinical medicine, Quality of life, chronic myeloid leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Internal medicine, medicine, Humans, dasatinib, Protein Kinase Inhibitors, Aged, business.industry, Case-control study, Myeloid leukemia, Cancer, chronic myeloid leukemia,imatinib,dasatinib,quality of life, Imatinib, Hematology, Middle Aged, medicine.disease, humanities, Clinical trial, Dasatinib, 030104 developmental biology, imatinib, quality of life, Case-Control Studies, 030220 oncology & carcinogenesis, Imatinib Mesylate, Female, Patient-reported outcome, business, medicine.drug
Abstract: There is paucity of evidence-based data on health-related quality of life (HRQOL) outcomes of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). We performed a multicenter propensity-matched case-control study to compare HRQOL of newly diagnosed CML patients treated with front-line dasatinib (cases) or imatinib (controls). Patient-reported HRQOL was assessed with the EORTC QLQ-C30 and the EORTC QLQ-CML24 questionnaires. The impact on daily life scale of the EORTC QLQ-CML24 was selected a priori in the protocol as the primary HRQOL scale for the comparative analysis. Overall, 323 CML patients were enrolled of whom 223 in therapy with imatinib and 100 in therapy with dasatinib. Patients treated with dasatinib reported better disease-specific HRQOL outcomes in impact on daily life (Δ = 8.72, 95% confidence interval [CI]: 3.17-14.27, p = 0.002), satisfaction with social life (Δ = 13.45, 95% CI: 5.82-21.08, p = 0.001), and symptom burden (Δ = 7.69, 95% CI: 3.42-11.96, p = 0.001). Analysis by age groups showed that, in patients aged 60 years and over, differences favoring dasatinib were negligible across several cancer generic and disease-specific HRQOL domains. Our findings provide novel comparative HRQOL data that extends knowledge on safety and efficacy of these two TKIs and may help to facilitate first-line treatment decisions.
Published: 2019
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16. Perspectives and Emotional Experiences of Patients With Chronic Myeloid Leukemia During ENESTPath Clinical Trial and Treatment-Free Remission: Rationale and Protocol of the Italian Substudy

Author: Elena Vegni, Chiara Elena, Gianantonio Rosti, Eros Di Bona, Simona Sica, Claudia Minotto, Gaetano La Barba, Sharon Supekar, Flavia Rivellini, Massimo Breccia, Luca Arcaini, Fabio Ciceri, I Capodanno, Sara Galimberti, Luigi Di Caprio, Antonio Cuneo, Alessandro Maggi, Paolo Sportoletti, Alessandra Iurlo, Giovanna Rege Cambrin, Enrico Capochiani, Francesco Albano, Lidia Borghi, Michele Baccarani, Massimiliano Bonifacio, Monica Crugnola, Borghi, L., Rosti, G., Maggi, A., Breccia, M., Di Bona, E., Iurlo, A., La Barba, G., Sportoletti, P., Albano, F., Galimberti, S., Rivellini, F., Cambrin, G. R., Capodanno, I., Cuneo, A., Bonifacio, M., Sica, S., Arcaini, L., Capochiani, E., Minotto, C., Ciceri, F., Crugnola, M., Di Caprio, L., Supekar, S., Elena, C., Baccarani, M., and Vegni, E.
Subjects: 0301 basic medicine, Cancer Research, Pediatrics, medicine.medical_specialty, Randomization, Chronic myeloid leukemia, ENESTPath, emotional experience, mixed methods, nilotinib, psychological distress, quality of life, study protocol, Dysfunctional family, NO, 03 medical and health sciences, 0302 clinical medicine, Quality of life, medicine, Methods, RC254-282, business.industry, Myeloid leukemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Imatinib, Clinical trial, Distress, 030104 developmental biology, Nilotinib, Oncology, 030220 oncology & carcinogenesis, business, medicine.drug
Abstract: Achievement of deep molecular response following treatment with a tyrosine kinase inhibitor (TKI) allows for treatment-free remission (TFR) in many patients with chronic myeloid leukemia (CML). Successful TFR is defined as the achievement of a sustained molecular response after cessation of ongoing TKI therapy. The phase 3 ENESTPath study was designed to determine the required optimal duration of consolidation treatment with the second-generation TKI, nilotinib 300 mg twice-daily, to remain in successful TFR without relapse after entering TFR for 12 months. The purpose of this Italian ‘patient’s voice CML’ substudy was to evaluate patients’ psycho-emotional characteristics and quality of life through their experiences of stopping treatment with nilotinib and entering TFR. The purpose of the present contribution is to early present the study protocol of an ongoing study to the scientific community, in order to describe the study rationale and to extensively present the study methodology. Patients aged ≥18 years with a confirmed diagnosis of Philadelphia chromosome positive BCR-ABL1+ CML in chronic phase and treated with front-line imatinib for a minimum of 24 months from the enrollment were eligible. Patients consenting to participate the substudy will have quality of life questionnaires and in-depth qualitative interviews conducted. The substudy will include both qualitative and quantitative design aspects to evaluate the psychological outcomes as assessed via patients’ emotional experience during and after stopping nilotinib therapy. Randomization is hypothesized to be a timepoint of higher psychological alert or distress when compared to consolidation and additionally any improvement in health-related quality of life (HRQoL) due to nilotinib treatment is expected across the timepoints (from consolidation, to randomization, and TFR). An association is also expected between dysfunctional coping strategies, such as detachments and certain personality traits, and psychological distress and HRQoL impairments. Better HRQoL outcomes are expected in TFR compared to the end of consolidation. This substudy is designed for in-depth assessment of all potential psycho-emotional variables and aims to determine the need for personalized patient care and counselling, and also guide clinicians to consider the psychological well-being of patients who are considering treatment termination.NCT number: NCT01743989, EudraCT number: 2012-005124-15
Published: 2021
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17. Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome

Author: Costanza Bosi, Nicola Vianelli, Fabrizio Pane, Giovanni Caocci, Massimiliano Bonifacio, Mario Tiribelli, Michele Cavo, Malgorzata Monika Trawinska, Daniela Bartoletti, Mauro Krampera, Giuseppe Auteri, Giulia Benevolo, Bruno Martino, Daniele Cattaneo, Roberto M. Lemoli, Giuseppe A. Palumbo, Nicola Polverelli, Massimo Breccia, Luigi Scaffidi, Monica Crugnola, Elisabetta Abruzzese, Antonio Cuneo, Florian H. Heidel, Elena Maria Elli, Elena Masselli, Francesca Palandri, Roberto Latagliata, Francesco Cavazzini, Alessandra Iurlo, Novella Pugliese, Rossella Stella, Giorgia Micucci, Alessia Tieghi, Gianpietro Semenzato, Gianni Binotto, Palandri F., Tiribelli M., Breccia M., Bartoletti D., Elli E.M., Benevolo G., Martino B., Cavazzini F., Tieghi A., Iurlo A., Abruzzese E., Pugliese N., Binotto G., Caocci G., Auteri G., Cattaneo D., Trawinska M.M., Stella R., Scaffidi L., Polverelli N., Micucci G., Masselli E., Crugnola M., Bosi C., Heidel F.H., Latagliata R., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Cavo M., Vianelli N., Bonifacio M., and Palumbo G.A.
Subjects: Cancer Research, medicine.medical_specialty, Disease status, Ruxolitinib, ruxolitinib, rechallenge, myelofibrosis, NO, 03 medical and health sciences, 0302 clinical medicine, myelofibrosi, Internal medicine, Nitriles, Overall survival, Medicine, cancer, Humans, In patient, 030212 general & internal medicine, Myelofibrosis, Retrospective Studies, outcome, business.industry, Therapeutic effect, Retrospective cohort study, medicine.disease, Discontinuation, Pyrimidines, Treatment Outcome, Oncology, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Pyrazoles, business, medicine.drug
Abstract: BACKGROUND: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P =.004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P 10 mg twice daily predicted better spleen (P =.05) and symptom improvements (P =.02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P =.004). CONCLUSIONS: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.
Published: 2021

18. Eutos long-term survival score discriminates different Sokal score categories in chronic myeloid leukemia patients, showing better survival prediction. Analysis of the {GIMEMA} {CML} observational study

Author: Giovannino Ciccone, Gaetano La Barba, Giovanni Caocci, Mario Tiribelli, Anna Rita Scortechini, Bruno Martino, Giuseppe Saglio, Massimo Breccia, Antonella Gozzini, Michele Pizzuti, Fausto Castagnetti, Massimiliano Bonifacio, Fabio Stagno, Patrizia Pregno, Luigiana Luciano, Giorgina Specchia, Breccia M., Pregno P., Castagnetti F., Bonifacio M., Tiribelli M., Gozzini A., Scortechini A.R., Luciano L., Martino B., Stagno F., Caocci G., La Barba G., Pizzuti M., Ciccone G., Saglio G., and Specchia G.
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Outcome Assessment, Prognosi, Dasatinib, Severity of Illness Index, Follow-Up Studie, Retrospective Studie, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, medicine, Humans, Prospective Studies, Chronic, Prospective cohort study, Survival rate, Aged, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocol, Leukemia, business.industry, Myeloid leukemia, Retrospective cohort study, Hematology, Middle Aged, Prognosis, Survival Rate, Health Care, Prospective Studie, Imatinib mesylate, Pyrimidines, Pyrimidine, Imatinib Mesylate, Observational study, Female, BCR-ABL Positive, Sokal Score, business, medicine.drug, Human, Follow-Up Studies, Myelogenous
Abstract: NA
Published: 2021

19. Prognostic Factors for Overall Survival In Chronic Myeloid Leukemia Patients: A Multicentric Cohort Study by the Italian CML GIMEMA Network

Author: Giovanni Reddiconto, Maria Stella De Candia, Sara Galimberti, Fabrizio Pane, Michele Pizzuti, Luciano Levato, Massimiliano Bonifacio, Massimo Breccia, Anna Rita Scortechini, Elisabetta Abruzzese, Giovanni Caocci, Valentina Giai, Paolo Ditonno, Andrea Patriarca, Federica Sorà, Giuseppe Pietrantuono, Gaetano La Barba, Fabio Stagno, Patrizia Pregno, Antonella Gozzini, Francesco Di Raimondo, Michele Baccarani, Grazia Sanpaolo, Giovannino Ciccone, Micaela Bergamaschi, Gianni Binotto, Alessandro Maggi, Chiara Monagheddu, Giuseppe Saglio, Maria Cristina Miggiano, Monica Bocchia, Pellegrino Musto, Anna Guella, Luigiana Luciano, Giorgina Specchia, Bruno Martino, Francesco Albano, Fabio Saccona, Giovanna Rege-Cambrin, Olga Mulas, Gianantonio Rosti, Carmen Fava, Mario Tiribelli, Fausto Castagnetti, Isabella Capodanno, Specchia G., Pregno P., Breccia M., Castagnetti F., Monagheddu C., Bonifacio M., Tiribelli M., Stagno F., Caocci G., Martino B., Luciano L., Pizzuti M., Gozzini A., Scortechini A.R., Albano F., Bergamaschi M., Capodanno I., Patriarca A., Fava C., Rege-Cambrin G., Sora F., Galimberti S., Bocchia M., Binotto G., Reddiconto G., DiTonno P., Maggi A., Sanpaolo G., De Candia M.S., Giai V., Abruzzese E., Miggiano M.C., La Barba G., Pietrantuono G., Guella A., Levato L., Mulas O., Saccona F., Rosti G., Musto P., Di Raimondo F., Pane F., Baccarani M., Saglio G., and Ciccone G.
Subjects: ELT, chronic myeloid leukemia, ELTs, prognostic factors, Sokal score, tyrosine kinase inhibitors, Cancer Research, medicine.medical_specialty, Patient characteristics, Internal medicine, Overall survival, Medicine, Prospective cohort study, prognostic factor, RC254-282, Original Research, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Imatinib, prognostic factors for overall survival in chronic myeloid leukemia patient a multicentric cohort study, Settore MED/15 - MALATTIE DEL SANGUE, Oncology, Cohort, business, Sokal Score, Cohort study, medicine.drug
Abstract: An observational prospective study was conducted by the CML Italian network to analyze the role of baseline patient characteristics and first line treatments on overall survival and CML-related mortality in 1206 newly diagnosed CML patients, 608 treated with imatinib (IMA) and 598 with 2nd generation tyrosine kinase inhibitors (2GTKI). IMA-treated patients were much older (median age 69 years, IQR 58-77) than the 2GTKI group (52, IQR 41-63) and had more comorbidities. Estimated 4-year overall survival of the entire cohort was 89% (95%CI 85.9-91.4). Overall, 73 patients (6.1%) died: 17 (2.8%) in the 2GTKI vs 56 (9.2%) in the IMA cohort (adjusted HR=0.50; 95% CI=0.26-0.94), but no differences were detected for CML-related mortality (10 (1.7%) vs 11 (1.8%) in the 2GTKIs vs IMA cohort (sHR=1.61; 0.52-4.96). The ELTS score was associated to CML mortality (high risk vs low, HR=9.67; 95%CI 2.94-31.74; p
Published: 2021

20. Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis

Author: Lisann Pelzl, Gabriela Constantin, Pietro Pucci, Emilia Turco, Immacolata Andolfo, Enrica Caterina Pietronigro, Francesca Garello, Kevin Peikert, Giuseppe Bertini, Enrica Federti, Maria Chiara Monti, Elena Tibaldi, Seth L. Alper, Mario Rosario Buffelli, Erika Lorenzetto, Flora Cozzolino, Angela Amoresano, Andreas Hermann, Alessandro Matte, Carlo Zancanaro, Anna Maria Brunati, Paola Defilippi, Massimiliano Bonifacio, Rainer Ordemann, Enzo Terreno, Adrian Danek, Lucia De Franceschi, Katja Akgün, Angela Siciliano, Federico Del Gallo, Hannes Glaß, Achille Iolascon, Paolo F. Fabene, Tjalf Ziemssen, Anna Illiano, Ruth H. Walker, Florian Lang, Peikert, K., Federti, E., Matte, A., Constantin, G., Pietronigro, E. C., Fabene, P. F., Defilippi, P., Turco, E., Del Gallo, F., Pucci, P., Amoresano, A., Illiano, A., Cozzolino, F., Monti, M., Garello, F., Terreno, E., Alper, S. L., Glass, H., Pelzl, L., Akgun, K., Ziemssen, T., Ordemann, R., Lang, F., Brunati, A. M., Tibaldi, E., Andolfo, I., Iolascon, A., Bertini, G., Buffelli, M., Zancanaro, C., Lorenzetto, E., Siciliano, A., Bonifacio, M., Danek, A., Walker, R. H., Hermann, A., and De Franceschi, L.
Subjects: Male, Cell signaling, Dasatinib, Vesicular Transport Proteins, Mice, Drug Delivery Systems, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, Chorea acanthocytosis, Mice, Knockout, 0303 health sciences, Neurodegeneration, Neuroacanthocytosi, 3. Good health, src-Family Kinases, Basal ganglia, Female, Tyrosine kinase, Neuroacanthocytosis, medicine.drug, Protein Kinase Inhibitor, Chorein, Lyn, Cell signaling, Basal ganglia, Neurodegeneration, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Vesicular Transport Protein, LYN, Animals, RC346-429, Lyn, Protein Kinase Inhibitors, Neuroinflammation, 030304 developmental biology, Animal, business.industry, Chorein, Research, Autophagy, medicine.disease, Mice, Inbred C57BL, Pyrimidines, Pyrimidine, Nilotinib, Cancer research, Neurology. Diseases of the nervous system, Neurology (clinical), business, Drug Delivery System, 030217 neurology & neurosurgery
Abstract: Chorea-Acanthocytosis (ChAc) is a devastating, little understood, and currently untreatable neurodegenerative disease caused by VPS13A mutations. Based on our recent demonstration that accumulation of activated Lyn tyrosine kinase is a key pathophysiological event in human ChAc cells, we took advantage of Vps13a−/− mice, which phenocopied human ChAc. Using proteomic approach, we found accumulation of active Lyn, γ-synuclein and phospho-tau proteins in Vps13a−/− basal ganglia secondary to impaired autophagy leading to neuroinflammation. Mice double knockout Vps13a−/− Lyn−/− showed normalization of red cell morphology and improvement of autophagy in basal ganglia. We then in vivo tested pharmacologic inhibitors of Lyn: dasatinib and nilotinib. Dasatinib failed to cross the mouse brain blood barrier (BBB), but the more specific Lyn kinase inhibitor nilotinib, crosses the BBB. Nilotinib ameliorates both Vps13a−/− hematological and neurological phenotypes, improving autophagy and preventing neuroinflammation. Our data support the proposal to repurpose nilotinib as new therapeutic option for ChAc patients.
Published: 2021

21. Making Treatment-Free Remission (TFR) Easier in Chronic Myeloid Leukemia: Fact-Checking and Practical Management Tools

Author: Maria Cristina Miggiano, Marzia Salvucci, Massimiliano Bonifacio, Elisabetta Calistri, Monica Poggiaspalla, Gianni Binotto, Atto Billio, Claudia Minotto, Alessandro Lucchesi, Elena Trabacchi, Francesco Cavazzini, Anna Merli, Mauro Krampera, Sara Galimberti, Antonella Gozzini, Isabella Capodanno, Gabriele Gugliotta, Barbara Scappini, Mario Tiribelli, Gianantonio Rosti, Monica Crugnola, Fausto Castagnetti, Castagnetti F., Binotto G., Capodanno I., Billio A., Calistri E., Cavazzini F., Crugnola M., Gozzini A., Gugliotta G., Krampera M., Lucchesi A., Merli A., Miggiano M.C., Minotto C., Poggiaspalla M., Salvucci M., Scappini B., Tiribelli M., Trabacchi E., Rosti G., Galimberti S., and Bonifacio M.
Subjects: Cancer Research, medicine.medical_specialty, Standard of care, Fact checking, Socio-culturale, Disease, chronic-phase chronic myeloid leukemia, tyrosine kinase inhibitors, treatment-free remission, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Early prediction, medicine, Humans, Pharmacology (medical), Intensive care medicine, Protein Kinase Inhibitors, business.industry, Remission Induction, Therapy in Practice, Myeloid leukemia, Female sex, Prognosis, Discontinuation, Treatment Outcome, Oncology, Disease risk, Female, business
Abstract: In chronic-phase chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) are the standard of care, and treatment-free remission (TFR) following the achievement of a stable deep molecular response (DMR) has become, alongside survival, a primary goal for virtually all patients. The GIMEMA CML working party recently suggested that the possibility of achieving TFR cannot be denied to any patient, and proposed specific treatment policies according to the patient’s age and risk. However, other international recommendations (including 2020 ELN recommendations) are more focused on survival and provide less detailed suggestions on how to choose first and subsequent lines of treatment. Consequently, some grey areas remain. After literature review, a panel of Italian experts discussed the following controversial issues: (1) early prediction of DMR and TFR: female sex, non-high disease risk score, e14a2 transcript and early MR achievement have been associated with stable DMR, but the lack of these criteria is not sufficient to exclude any patient from TFR; (2) criteria for first and subsequent line therapy choice: a number of patient and drug characteristics have been proposed to make a personalized decision; (3) monitoring of residual disease after discontinuation: after the first 6 months, the frequency of molecular tests can be reduced based on MR4.5 persistence and short turnaround time; (4) prognosis of TFR: therapy and DMR duration are important to predict TFR; although immunological control of CML plays a role, no immunological predictive phenotype is currently available. This guidance is intended as a practical tool to support physicians in decision making.
Published: 2021

22. Next-generation sequencing improves BCR-ABL1 mutation detection in Philadelphia chromosome-positive acute lymphoblastic leukaemia

Author: Fabio Stagno, Flavio Mignone, Erika Borlenghi, Elena Maino, Cristina Papayannidis, Simona Soverini, Manuela Stulle, Annalisa Imovilli, Claudia Basilico, Sabina Russo, Claudio Fozza, Chiara Sartor, Stefania Stella, Michele Cavo, Mario Annunziata, Roberta Minari, Federica Sorà, Michele Baccarani, Caterina De Benedittis, Luana Bavaro, Margherita Martelli, Francesco Albano, Massimiliano Bonifacio, Giovanni Martinelli, Elisabetta Abruzzese, Sara Galimberti, Soverini S., Martelli M., Bavaro L., De Benedittis C., Papayannidis C., Sartor C., Sora F., Albano F., Galimberti S., Abruzzese E., Annunziata M., Russo S., Stulle M., Imovilli A., Bonifacio M., Maino E., Stagno F., Maria Basilico C., Borlenghi E., Fozza C., Mignone F., Minari R., Stella S., Baccarani M., Cavo M., and Martinelli G.
Subjects: Oncology, Male, Neoplasm, Residual, bcr-abl, Drug Resistance, Fusion Proteins, bcr-abl, medicine.disease_cause, Tyrosine-kinase inhibitor, 0302 clinical medicine, hemic and lymphatic diseases, tyrosine kinase inhibitors, Medicine, Philadelphia Chromosome, Sanger sequencing, Mutation, Philadelphia Chromosome Positive, High-Throughput Nucleotide Sequencing, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, acute lymphoblastic leukemia, BCR-ABL1, mutations, NGS, Adult, Aged, Clinical Decision-Making, Drug Resistance, Neoplasm, Female, Humans, Protein Kinase Inhibitors, Residual, 030220 oncology & carcinogenesis, symbols, medicine.medical_specialty, medicine.drug_class, DNA sequencing, 03 medical and health sciences, symbols.namesake, Internal medicine, business.industry, Fusion Proteins, Minimal residual disease, Mutation testing, Neoplasm, Lymphoblastic leukaemia, business, 030215 immunology
Abstract: BCR-ABL1 kinase domain mutation testing in tyrosine kinase inhibitor (TKI)-resistant Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) patients is routinely performed by Sanger sequencing (SS). Recently, next-generation sequencing (NGS)-based approaches have been developed that afford greater sensitivity and straightforward discrimination between compound and polyclonal mutations. We performed a study to compare the results of SS and NGS in a consecutive cohort of 171 Ph+ ALL patients. At diagnosis, 0/44 and 3/44 patients were positive for mutations by SS and NGS respectively. Out of 47 patients with haematologic resistance, 45 had mutations according to both methods, but in 25 patients NGS revealed additional mutations undetectable by SS. Out of 80 patients in complete haematologic response but with BCR-ABL1 ≥0·1%, 28 (35%) and 52 (65%) were positive by SS and NGS respectively. Moreover, in 12 patients positive by SS, NGS detected additional mutations. NGS resolved clonal complexity in 34 patients with multiple mutations at the same or different codons and identified 35 compound mutations. Our study demonstrates that, in Ph+ ALL on TKI therapy, NGS enables more accurate assessment of mutation status both in patients who fail therapy and in patients with minimal residual disease above 0·1%.
Published: 2020

23. Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib

Author: Fabio Stagno, Patrizia Pregno, Giovanni Caocci, Gianni Binotto, Robin Foà, Anna Sicuranza, Emilia Scalzulli, Francesca Pirillo, Mario Tiribelli, Isabella Capodanno, Antonella Gozzini, Massimiliano Bonifacio, Rossella Stella, Elisabetta Abruzzese, Massimo Breccia, Claudio Fozza, Gabriele Gugliotta, Giorgio La Nasa, Luigiana Luciano, Olga Mulas, Maria Pina Simula, Daniele Cattaneo, Mario Annunziata, Francesco Albano, Luigi Scaffidi, Fiorenza De Gregorio, Debora Luzi, Claudia Baratè, Malgorzata Monika Trawinska, Immacolata Attolico, Fabio Efficace, Sara Galimberti, Fausto Castagnetti, Monica Bocchia, Bruno Martino, Alessandra Iurlo, Caocci G., Mulas O., Capodanno I., Bonifacio M., Annunziata M., Galimberti S., Luciano L., Tiribelli M., Martino B., Castagnetti F., Binotto G., Pregno P., Stagno F., Abruzzese E., Bocchia M., Gozzini A., Albano F., Fozza C., Luzi D., Efficace F., Simula M.P., Scaffidi L., Barate C., De Gregorio F., Stella R., Gugliotta G., Pirillo F., Trawinska M.M., Sicuranza A., Cattaneo D., Attolico I., Scalzulli E., Iurlo A., Foa R., Breccia M., and La Nasa G.
Subjects: Male, Arterial Occlusive Disease, Triglyceride, Gastroenterology, Antineoplastic Agent, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, 80 and over, Cumulative incidence, Chronic, Aged, 80 and over, Leukemia, Incidence (epidemiology), Chronic myeloid leukemia, Hematology, General Medicine, Middle Aged, Lipoproteins, LDL, Cholesterol, 030220 oncology & carcinogenesis, Low-density lipoprotein, Female, Human, medicine.drug, Adult, medicine.medical_specialty, Lipoproteins, Arterial occlusive event, Antineoplastic Agents, Arterial Occlusive Diseases, Lower risk, High cholesterol, LDL, 03 medical and health sciences, Young Adult, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Triglycerides, Aged, Dyslipidemias, business.industry, Risk Factor, Nilotinib, medicine.disease, Pyrimidines, Dyslipidemia, Pyrimidine, chemistry, BCR-ABL Positive, business, 030215 immunology, Myelogenous
Abstract: Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200mg/dL and LDL > 70mg/dL 3months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P= 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P< 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P= 0.008; HR = 3.5; 95% CI = 1.4–8.7 and P < 0.001; HR = 4.4; 95% CI = 2–9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins. Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.
Published: 2020

24. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis

Author: Bruno Martino, Daniele Cattaneo, Florian H. Heidel, Elisabetta Abruzzese, Gianni Binotto, Rossella Stella, Giulia Benevolo, Michele Cavo, Micaela Bergamaschi, Roberto Latagliata, Francesco Cavazzini, Novella Pugliese, Massimo Breccia, Alessandro Isidori, Gianpietro Semenzato, Daniela Bartoletti, Mauro Krampera, Malgorzata Monica Trawinska, Costanza Bosi, Giovanni Caocci, Fabrizio Pane, Alessia Tieghi, Francesca Palandri, Roberto M. Lemoli, Elena Maria Elli, Antonio Cuneo, Fiorella Ciantia, Alessandra Iurlo, Monica Crugnola, Giuseppe Auteri, Mario Tiribelli, Massimiliano Bonifacio, Nicola Vianelli, Luigi Scaffidi, Giuseppe A. Palumbo, Nicola Polverelli, Palandri F., Palumbo G.A., Elli E.M., Polverelli N., Benevolo G., Martino B., Abruzzese E., Tiribelli M., Tieghi A., Latagliata R., Cavazzini F., Bergamaschi M., Binotto G., Crugnola M., Isidori A., Caocci G., Heidel F., Pugliese N., Bosi C., Bartoletti D., Auteri G., Cattaneo D., Scaffidi L., Trawinska M.M., Stella R., Ciantia F., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Iurlo A., Vianelli N., Cavo M., Breccia M., and Bonifacio M.
Subjects: Ruxolitinib, medicine.medical_specialty, Humans, Janus Kinases, Multivariate Analysis, Primary Myelofibrosis, Protein Kinase Inhibitors, Pyrazoles, Risk Factors, Treatment Outcome, medicine.medical_treatment, Splenectomy, lcsh:RC254-282, Nitriles, Pyrimidines, Ruxolitinib discontinuation syndrome, risk factors, myelofibrosis, NO, Myeloproliferative disease, Internal medicine, Correspondence, medicine, Risk factor, Bone pain, Myelofibrosis, Respiratory distress, business.industry, Incidence (epidemiology), Hematology, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Discontinuation, Oncology, medicine.symptom, business, Haematological diseases, medicine.drug
Abstract: No abstract available
Published: 2020

25. Current Strategies and Future Directions to Achieve Deep Molecular Response and Treatment-Free Remission in Chronic Myeloid Leukemia

Author: Massimiliano Bonifacio, Antonella Gozzini, Fausto Castagnetti, Giorgina Specchia, Alessandra Iurlo, Massimo Breccia, Fabio Stagno, Patrizia Pregno, Mario Annunziata, Annunziata M., Bonifacio M., Breccia M., Castagnetti F., Gozzini A., Iurlo A., Pregno P., Stagno F., and Specchia G.
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Treatment goals, Review, optimal strategies, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, chronic myeloid leukemia, Internal medicine, hemic and lymphatic diseases, tyrosine kinase inhibitors, Medicine, In patient, Kinase activity, treatment-free remission, business.industry, optimal strategie, Myeloid leukemia, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, deep molecular response, 030104 developmental biology, Chronic disease, Nilotinib, 030220 oncology & carcinogenesis, Molecular Response, Patient communication, business, medicine.drug
Abstract: The treatment of chronic myeloid leukemia (CML) has been radically changed by the approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity. CML is now managed as a chronic disease requiring long-term treatment and close molecular monitoring. It has been shown that in a substantial number of patients who have achieved a stable deep molecular response (DMR), TKI treatment can be safely discontinued without loss of response. Therefore, treatment-free remission (TFR), through the achievement of a DMR, is increasingly regarded as a feasible treatment goal in many CML patients. However, only nilotinib has approval in this setting and a number of controversial aspects remain regarding treatment choices and timings, predictive factors, patient communication, and optimal strategies to achieve successful TFR. This narrative review aims to provide a comprehensive overview on how to optimize the path to DMR and TFR in patients with CML, and discusses recent data and future directions.
Published: 2020
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26. Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors

Author: Chiara Elena, Alessandra Iurlo, Antonella Gozzini, Giorgio La Nasa, Claudia Baratè, Gabriele Gugliotta, Bruno Martino, Francesca Pirillo, Fiorenza De Gregorio, Fabio Efficace, Monica Bocchia, Massimo Breccia, Claudio Fozza, Elisabetta Abruzzese, Mario Annunziata, Sara Galimberti, Gianni Binotto, Fabio Stagno, Isabella Capodanno, Malgorzata Monika Trawinska, Anna Sicuranza, Maria Pina Simula, Robin Foà, Debora Luzi, Patrizia Pregno, Rossella Stella, Imma Attolico, Luigiana Luciano, Francesco Albano, Giovanni Caocci, Ester Orlandi, Daniele Cattaneo, Olga Mulas, Nicola Sgherza, Luigi Scaffidi, Massimiliano Bonifacio, Emilia Scalzulli, Mario Tiribelli, Fausto Castagnetti, Mulas O., Caocci G., Stagno F., Bonifacio M., Annunziata M., Luciano L., Orlandi E.M., Abruzzese E., Sgherza N., Martino B., Albano F., Galimberti S., Pregno P., Bocchia M., Castagnetti F., Tiribelli M., Binotto G., Gozzini A., Capodanno I., Fozza C., Luzi D., Efficace F., Simula M.P., Scaffidi L., De Gregorio F., Elena C., Trawinska M.M., Cattaneo D., Attolico I., Barate C., Pirillo F., Sicuranza A., Gugliotta G., Stella R., Scalzulli E., Iurlo A., Foa R., Breccia M., and La Nasa G.
Subjects: Male, Myeloid, Angiotensin-Converting Enzyme Inhibitors, Gastroenterology, Cohort Studies, Renin-Angiotensin System, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, 80 and over, Cumulative incidence, Chronic, Aged, 80 and over, Leukemia, Arterial occlusive events, Incidence, Ponatinib, Angiotensin Receptor Antagonist, Chronic myeloid leukemia, Myeloid leukemia, Hematology, General Medicine, Middle Aged, TKI, Dasatinib, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Combination, Hypertension, Drug Therapy, Combination, Female, Survival Analysi, medicine.drug, Human, Renin angiotensin system inhibitors, Adult, medicine.medical_specialty, Arterial occlusive event, Protein Kinase Inhibitor, 03 medical and health sciences, Angiotensin Receptor Antagonists, Drug Therapy, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Artery occlusion, Protein Kinase Inhibitors, Aged, business.industry, Risk Factor, Angiotensin-Converting Enzyme Inhibitor, Thrombosis, Renin angiotensin system inhibitor, Survival Analysis, Blood pressure, chemistry, Nilotinib, BCR-ABL Positive, Cohort Studie, business, 030215 immunology, Myelogenous
Abstract: Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their additional cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-year cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rdG TKIs.
Published: 2020

27. Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: The NEXT-in-CML study

Author: Anna Serra, Antonio Percesepe, Gabriele Gugliotta, Caterina Musolino, Gianni Binotto, Elisabetta Abruzzese, Immacolata Attolico, Gianantonio Rosti, Mario Annunziata, Rosaria Sancetta, Mariella Girasoli, Fabrizio Pane, Maria Antonella Laginestra, Sara Galimberti, Alessandra Iurlo, Stefania Stella, Sabrina Coluzzi, Simona Sica, Monica Bocchia, Marzia Salvucci, Francesca Lunghi, Fabio Stagno, Nicola Orofino, Stefano Pileri, Federica Sorà, Santa Errichiello, Elisabetta Calistri, Paolo Vigneri, Fausto Castagnetti, Michele Baccarani, Luana Bavaro, Michele Cavo, Eros Di Bona, Francesco Di Raimondo, Claudia Baratè, Margherita Martelli, Simona Soverini, Antonella Russo Rossi, Francesco Albano, Mariella D'Adda, Fabio Ciceri, Flavio Mignone, Elena Tenti, Caterina De Benedittis, Giuseppe Saglio, Isabella Capodanno, Giovanni Martinelli, Massimiliano Bonifacio, Luigi Scaffidi, Soverini, S., Bavaro, L., de Benedittis, C., Martelli, M., Iurlo, A., Orofino, N., Sica, S., Sora, F., Lunghi, F., Ciceri, F., Galimberti, S., Barate, C., Bonifacio, M., Scaffidi, L., Castagnetti, F., Gugliotta, G., Albano, F., Rossi, A. V. R., Stagno, F., di Raimondo, F., D'Adda, M., di Bona, E., Abruzzese, E., Binotto, G., Sancetta, R., Salvucci, M., Capodanno, I., Girasoli, M., Coluzzi, S., Attolico, I., Musolino, C., Calistri, E., Annunziata, M., Bocchia, M., Stella, S., Serra, A., Errichiello, S., Saglio, G., Pane, F., Vigneri, P., Mignone, F., Laginestra, M. A., Pileri, S. A., Percesepe, A., Tenti, E., Rosti, G., Baccarani, M., Cavo, M., Martinelli, G., Soverini, Simona, Bavaro, Luana, De Benedittis, Caterina, Martelli, Margherita, Iurlo, Alessandra, Orofino, Nicola, Sica, Simona, Sora, Federica, Lunghi, Francesca, Ciceri, Fabio, Galimberti, Sara, Baratè, Claudia, Bonifacio, Massimiliano, Scaffidi, Luigi, Castagnetti, Fausto, Gugliotta, Gabriele, Albano, Francesco, Russo Rossi, Antonella Vita, Stagno, Fabio, Di Raimondo, Francesco, D'Adda, Mariella, Di Bona, Ero, Abruzzese, Elisabetta, Binotto, Gianni, Sancetta, Rosaria, Salvucci, Marzia, Capodanno, Isabella, Girasoli, Mariella, Coluzzi, Sabrina, Attolico, Immacolata, Musolino, Caterina, Calistri, Elisabetta, Annunziata, Mario, Bocchia, Monica, Stella, Stefania, Serra, Anna, Errichiello, Santa, Saglio, Giuseppe, Pane, Fabrizio, Vigneri, Paolo G, Mignone, Flavio, Laginestra, Maria Antonella, Pileri, Stefano A, Percesepe, Antonio, Tenti, Elena, Rosti, Gianantonio, Baccarani, Michele, Cavo, Michele, and Martinelli, Giovanni
Subjects: Oncology, Male, Mutation rate, bcr-abl, Drug Resistance, Fusion Proteins, bcr-abl, Gene mutation, medicine.disease_cause, Settore MED/01 - STATISTICA MEDICA, Biochemistry, Adult, Aged, Aged, 80 and over, Drug Resistance, Neoplasm, Female, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Middle Aged, Mutation, Mutation Rate, Prospective Studies, Protein Kinase Inhibitors, hemic and lymphatic diseases, 80 and over, cml mutation, BCR-ABL mutations, Chronic, Prospective cohort study, Sanger sequencing, Leukemia, Chronic myeloid leukemia, Myeloid leukemia, Hematology, TKI, NGS, symbols, Human, medicine.medical_specialty, Immunology, symbols.namesake, CML, TKIs, BCR-ABL1, Chronic myeloid leukemia,TKI,BCR-ABL mutations,Sanger Sequencing,NGS, Internal medicine, medicine, business.industry, Fusion Proteins, Cell Biology, medicine.disease, Clinical trial, Prospective Studie, Sanger Sequencing, Neoplasm, BCR-ABL Positive, business, Myelogenous
Abstract: In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.
Published: 2020

28. Risk factors for progression to blast phase and outcome in 589 patients with myelofibrosis treated with ruxolitinib: Real-world data

Author: Massimo Breccia, Mauro Krampera, Alessandro Isidori, Monica Crugnola, Daniela Bartoletti, Elena Maria Elli, Alessia Tieghi, Massimiliano Bonifacio, Micaela Bergamaschi, Costanza Bosi, Roberto Latagliata, Roberto M. Lemoli, Francesco Cavazzini, Florian H. Heidel, Michele Cavo, Nicola Polverelli, Malgorzata Monika Trawinska, Francesca Palandri, Bruno Martino, Daniele Cattaneo, Giulia Benevolo, Giuseppe Auteri, Elisabetta Abruzzese, Gianni Binotto, Alessandra Iurlo, Nicola Vianelli, Antonio Cuneo, Francesco Di Raimondo, Dorian Forte, Davide Griguolo, Gianpietro Semenzato, Giuseppe A. Palumbo, Mario Tiribelli, Palandri F., Breccia M., Tiribelli M., Bonifacio M., Benevolo G., Iurlo A., Elli E.M., Binotto G., Tieghi A., Polverelli N., Martino B., Abruzzese E., Bergamaschi M., Heidel F.H., Cavazzini F., Crugnola M., Bosi C., Isidori A., Auteri G., Forte D., Latagliata R., Griguolo D., Cattaneo D., Trawinska M., Bartoletti D., Krampera M., Semenzato G., Lemoli R.M., Cuneo A., Di Raimondo F., Vianelli N., Cavo M., and Palumbo G.A.
Subjects: Male, Cancer Research, Ruxolitinib, ruxolitinib, Gastroenterology, 0302 clinical medicine, myelofibrosi, 80 and over, risk factors, blast phase, myelofibrosis, outcome, Adult, Aged, Aged, 80 and over, Blast Crisis, Disease Progression, Female, Follow-Up Studies, Humans, Janus Kinases, Middle Aged, Primary Myelofibrosis, Prognosis, Pyrazoles, Retrospective Studies, Survival Rate, Young Adult, Incidence (epidemiology), Hematology, General Medicine, risk factor, Oncology, 030220 oncology & carcinogenesis, blast phase, myelofibrosis, outcome, risk factors, ruxolitinib, Blast Crisis, Disease Progression, medicine.drug, medicine.medical_specialty, Socio-culturale, Alpha interferon, 03 medical and health sciences, Internal medicine, Nitriles, medicine, Risk factor, Myelofibrosis, Survival rate, business.industry, Induction chemotherapy, Anagrelide, medicine.disease, Pyrimidines, business, 030215 immunology
Abstract: The impact of ruxolitinib therapy on evolution to blast phase (BP) in patients with myelofibrosis (MF) is still uncertain. In 589 MF patients treated with ruxolitinib, we investigated incidence and risk factors for BP and we described outcome according to disease characteristics and treatment strategy. After a median follow-up from ruxolitinib start of 3 years (range 0.1-7.6), 65 (11%) patients transformed to BP during (93.8%) or after treatment. BP incidence rate was 3.7 per 100 patient-years, comparably in primary and secondary MF (PMF/SMF) but significantly lower in intermediate-1 risk patients (2.3 vs 5.6 per 100 patient-years in intermediate-2/high-risk patients, P
Published: 2020

29. Favorable outcome of chronic myeloid leukemia co-expressing e13a2 and e14a2 transcripts, treated with nilotinib

Author: Sara Galimberti, Giovanni Caocci, Ester Orlandi, Mario Annunziata, Gabriele Gugliotta, Emilia Scalzulli, Alessandra Iurlo, Chiara Elena, Elisabetta Abruzzese, Daniele Cattaneo, Bruno Martino, Malgorzata Monika Trawinska, Giorgio La Nasa, Luigi Scaffidi, Francesca Pirillo, Anna Sicuranza, Luigiana Luciano, Fausto Castagnetti, Patrizia Pregno, Monica Bocchia, Nicola Sgherza, Francesco Albano, Robin Foà, Massimo Breccia, Fiorenza De Gregorio, Antonella Gozzini, Massimiliano Bonifacio, Claudia Baratè, Imma Attolico, Maria Pina Simula, Gianni Binotto, Claudio Fozza, Olga Mulas, Mulas O., Caocci G., Annunziata M., Martino B., Luciano L., Castagnetti F., Pregno P., Galimberti S., Albano F., Orlandi E.M., Sgherza N., Iurlo A., Bonifacio M., Binotto G., Gozzini A., Bocchia M., Abruzzese E., Fozza C., Simula M.P., De Gregorio F., Gugliotta G., Pirillo F., Barate C., Attolico I., Elena C., Cattaneo D., Scaffidi L., Sicuranza A., Trawinska M.M., Scalzulli E., Foa R., Breccia M., and La Nasa G.
Subjects: Oncology, Male, Cancer Research, Chromosomes, Human, Pair 22, bcr-abl, Messenger, Fusion Proteins, bcr-abl, Translocation, Genetic, 80 and over, Favorable outcome, RNA, Neoplasm, Chronic, Aged, 80 and over, Leukemia, Follow up studies, Myeloid leukemia, molecular response, Hematology, General Medicine, Middle Aged, Survival Rate, outcome, Female, Chromosomes, Human, Pair 9, medicine.drug, Human, Pair 9, Adult, medicine.medical_specialty, Disease free survival, transcript type, MEDLINE, Translocation, Disease-Free Survival, Chromosomes, Follow-Up Studie, Text mining, Genetic, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, RNA, Messenger, Survival rate, nilotinib, Aged, Follow-Up Studies, Pyrimidines, business.industry, chronic myeloid leukemia, nilotinib, transcript type, molecular response, outcome, Fusion Proteins, Nilotinib, Pyrimidine, RNA, Neoplasm, BCR-ABL Positive, Pair 22, business, Myelogenous
Abstract: No abstract available.
Published: 2020

30. Low low-density lipoprotein (LDL), cholesterol and triglycerides plasma levels are associated with reduced risk of arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life. A Campus CML study

Author: Emilia Scalzulli, Fabio Efficace, Giovanni Caocci, Ester Orlandi, Sara Galimberti, Mario Tiribelli, Daniele Cattaneo, Elisabetta Abruzzese, Luigi Scaffidi, Olga Mulas, Immacolata Attolico, Debora Luzi, Massimiliano Bonifacio, Robin Foà, Chiara Elena, Rossella Stella, Fausto Castagnetti, Massimo Breccia, Maria Pina Simula, Claudia Baratè, Luigiana Luciano, Malgorzata Monika Trawinska, Francesco Albano, Fabio Stagno, Patrizia Pregno, Antonella Gozzini, Gianni Binotto, Gabriele Gugliotta, Giorgio La Nasa, Francesca Pirillo, Nicola Sgherza, Mario Annunziata, Alessandra Iurlo, Claudio Fozza, Isabella Capodanno, Fiorenza De Gregorio, Caocci G., Mulas O., Capodanno I., Abruzzese E., Iurlo A., Luciano L., Albano F., Annunziata M., Tiribelli M., Bonifacio M., Galimberti S., Castagnetti F., Sgherza N., Stagno F., Gozzini A., Orlandi E.M., Luzi D., Binotto G., Pregno P., Fozza C., Efficace F., Simula M.P., Trawinska M.M., Cattaneo D., De Gregorio F., Attolico I., Stella R., Scaffidi L., Barate C., Gugliotta G., Scalzulli E., Elena C., Pirillo F., Foa R., Breccia M., and Nasa G.L.
Subjects: Adult, Male, medicine.medical_specialty, Antineoplastic Agents, Arterial Occlusive Diseases, Gastroenterology, lcsh:RC254-282, chronic myeloid leukemia, TKI, ponatinib, arterial occlusive events, Article, chemistry.chemical_compound, Young Adult, Myeloproliferative disease, High-density lipoprotein, Low low-density lipoprotein, LDL, cholesterol, triglycerides, arterial occlusive events, chronic myeloid leukemia, ponatinib, CML, Campus, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Medicine, Humans, ponatinib, Artery occlusion, arterial occlusive events, Triglycerides, Aged, Aged, 80 and over, business.industry, Cholesterol, Ponatinib, Imidazoles, Myeloid leukemia, Hematology, Middle Aged, Protective Factors, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, TKI, Lipoproteins, LDL, Pyridazines, Leukemia, Oncology, chemistry, Risk factors, Low-density lipoprotein, Female, business, Dyslipidemia
Abstract: Not available.
Published: 2020

31. Second primary malignancy in myelofibrosis patients treated with ruxolitinib

Author: Elena Maria Elli, Florian H. Heidel, Uros Markovic, Fabrizio Pane, Gianpietro Semenzato, Daniela Bartoletti, Francesca Palandri, Giulia Benevolo, Mauro Krampera, Malgorzata Monika Trawinska, Micaela Bergamaschi, Mario Tiribelli, Giovanni Caocci, Lucia Catani, Elisabetta Abruzzese, Massimo Breccia, Rossella Stella, Antonio Cuneo, Fabio D'Amore, Alessandro Isidori, Costanza Bosi, Monica Crugnola, Lisa Gandolfi, Domenico Russo, Alessandra Iurlo, Nicola Polverelli, Roberto M. Lemoli, Michele Cavo, Gianni Binotto, Roberto Latagliata, Francesco Cavazzini, Bruno Martino, Daniele Cattaneo, Nicola Vianelli, Novella Pugliese, Luigi Scaffidi, Massimiliano Bonifacio, Mariella D'Adda, Alessia Tieghi, Giuseppe Auteri, Giuseppe A. Palumbo, Polverelli N., Elli E.M., Abruzzese E., Palumbo G.A., Benevolo G., Tiribelli M., Bonifacio M., Tieghi A., Caocci G., D'Adda M., Bergamaschi M., Binotto G., Heidel F.H., Cavazzini F., Crugnola M., Pugliese N., Bosi C., Isidori A., Bartoletti D., Auteri G., Latagliata R., Gandolfi L., Martino B., Scaffidi L., Cattaneo D., D'Amore F., Trawinska M.M., Stella R., Markovic U., Catani L., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Vianelli N., Breccia M., Russo D., Cavo M., Iurlo A., and Palandri F.
Subjects: Male, Ruxolitinib, Skin Neoplasms, Lymphoma, ruxolitinib, Aggressive lymphoma, Gastroenterology, Hydroxycarbamide, 0302 clinical medicine, myelofibrosi, Risk Factors, Neoplasms, 80 and over, Aged, 80 and over, Thrombocytosis, Incidence (epidemiology), Incidence, Hazard ratio, Neoplasms, Second Primary, Hematology, Arteries, Middle Aged, Second Primary, JAK inhibitor, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Context (language use), myelofibrosis, JAK inhibitors, second cancer, toxicity, NO, 03 medical and health sciences, Internal medicine, Nitriles, medicine, Humans, Janus Kinase Inhibitors, Myelofibrosis, Aged, Retrospective Studies, business.industry, Thrombosis, medicine.disease, Case-Control Studies, Follow-Up Studies, Multivariate Analysis, Primary Myelofibrosis, Pyrazoles, Pyrimidines, business, 030215 immunology
Abstract: Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P=0·01] and thrombocytosis>400×109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17–8·75, P=0·02 and HR: 2·93, 95%CI: 1·39–6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P=0·03), platelet>400×109/l (HR: 3·30, 95%CI: 1·67–6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.
Published: 2020

32. Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second- and third-generation tyrosine kinase inhibitors

Author: Gabriele Gugliotta, Francesca Pirillo, Bruno Martino, Fausto Castagnetti, Chiara Elena, Antonella Gozzini, Giorgio La Nasa, Massimiliano Bonifacio, Claudia Baratè, Gianni Binotto, Robin Foà, Daniele Cattaneo, Nicola Sgherza, Alessandra Iurlo, Monica Bocchia, Elisabetta Abruzzese, Mario Annunziata, Claudio Fozza, Fiorenza De Gregorio, Matteo Molica, Luigi Scaffidi, Sara Galimberti, Olga Mulas, Giovanni Caocci, Imma Attolico, Ester Orlandi, Maria Pina Simula, Luigiana Luciano, Massimo Breccia, Francesco Albano, Fabio Stagno, Patrizia Pregno, Anna Sicuranza, Malgorzata Monika Trawinska, Caocci G., Mulas O., Annunziata M., Luciano L., Abruzzese E., Bonifacio M., Orlandi E.M., Albano F., Galimberti S., Iurlo A., Pregno P., Sgherza N., Martino B., Binotto G., Castagnetti F., Gozzini A., Bocchia M., Fozza C., Stagno F., Simula M.P., De Gregorio F., Trawinska M.M., Scaffidi L., Elena C., Attolico I., Barate C., Cattaneo D., Pirillo F., Gugliotta G., Sicuranza A., Molica M., La Nasa G., Foa R., and Breccia M.
Subjects: Male, Chronic myeloid leuk, Dasatinib, emia, Long Term Adverse Effects, Long Term Adverse Effect, 030204 cardiovascular system & hematology, Antineoplastic Agent, chemistry.chemical_compound, 0302 clinical medicine, Cardiovascular Disease, Cardiovascular toxicity, Ischemic heart disease, TKI, Aged, Antineoplastic Agents, Female, Humans, Italy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Life Expectancy, Mortality, Protein Kinase Inhibitors, Risk Adjustment, Aniline Compounds, Cardiotoxicity, Cardiovascular Diseases, Imidazoles, Nitriles, Pyridazines, Pyrimidines, Quinolines, 030212 general & internal medicine, Chronic, education.field_of_study, Leukemia, Mortality rate, Ponatinib, Aniline Compound, a, Pyridazine, Cardiology and Cardiovascular Medicine, Nitrile, Bosutinib, Human, medicine.drug, medicine.medical_specialty, Population, Protein Kinase Inhibitor, 03 medical and health sciences, Internal medicine, medicine, education, Imidazole, Survival rate, business.industry, Standardized mortality ratio, Pyrimidine, Nilotinib, chemistry, BCR-ABL Positive, business, Myelogenous
Abstract: Background Limited information is available regarding the rate of long-term cardiovascular (CV) mortality in chronic myeloid leukaemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (2ndG/3rdG TKIs) in the real-life practice. Methods We identified 656 consecutive CML patients treated with nilotinib, dasatinib, bosutinib and ponatinib. Results The 15-year CV-mortality free survival was 93 ± 2.8%. Age ≥65 years (p = 0.005) and a positive history of CV disease (p = 0.04) were significantly associated with a lower CV-mortality free survival. CV disease accounted for 16.5% and 5% of potential years of life lost (PYLL) in male and female patients, respectively. The standard mortality ratio (SMR) following ischemic heart disease (IHD) was 3.9 in males and 3.8 in female patients, meaning an excess of IHD deaths observed, in comparison with the population of control. Conclusion. Prevention strategies based on CV risk factors, in particular in those patients with a previous history of CV disease, should be considered.
Published: 2019

33. Recurrent arterial occlusive events in patients with chronic myeloid leukemia treated with second- and third-generation tyrosine kinase inhibitors and role of secondary prevention

Author: Claudio Fozza, Giovanni Caocci, Ester Orlandi, Massimiliano Bonifacio, Chiara Elena, Bruno Martino, Daniele Cattaneo, Mario Annunziata, Luigi Scaffidi, Antonella Gozzini, Sara Galimberti, Olga Mulas, Fabio Stagno, Gianni Binotto, Patrizia Pregno, Giorgio La Nasa, Robin Foà, Fausto Castagnetti, Alessandra Iurlo, Malgorzata Monika Trawinska, Massimo Breccia, Emilia Scalzulli, Luigiana Luciano, Francesco Albano, Claudia Baratè, Elisabetta Abruzzese, Caocci G., Mulas O., Bonifacio M., Abruzzese E., Galimberti S., Orlandi E.M., Iurlo A., Annunziata M., Luciano L., Castagnetti F., Gozzini A., Stagno F., Binotto G., Pregno P., Albano F., Martino B., Fozza C., Scaffidi L., Trawinska M.M., Barate C., Elena C., Cattaneo D., Scalzulli E., La Nasa G., Foa R., and Breccia M.
Subjects: Oncology, Male, Time Factors, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, Recurrent arterial occlusive event, Recurrence, Risk Factors, 80 and over, Secondary Prevention, Medicine, Cumulative incidence, 030212 general & internal medicine, Chronic, Aged, 80 and over, Chronic myeloid leukemia, Secondary prophylaxis, Leukemia, Incidence (epidemiology), Incidence, Ponatinib, Myeloid leukemia, Middle Aged, Aged, Anticoagulants, Arterial Occlusive Diseases, Female, Follow-Up Studies, Humans, Italy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Platelet Aggregation Inhibitors, Protein Kinase Inhibitors, Treatment Outcome, Dasatinib, Platelet aggregation inhibitor, Cardiology and Cardiovascular Medicine, Bosutinib, medicine.drug, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, business.industry, chemistry, Nilotinib, BCR-ABL Positive, business, Myelogenous
Abstract: Background Risk of death is particularly high in patients with a previous history of arterial occlusive events (AOEs) and the probability for a recurrent event is around 20%. Little is known about recurrent AOE and the role of secondary prevention in patients with Chronic Myeloid Leukemia (CML) with previous AOE, treated with second- and third-generation tyrosine kinase inhibitors (2ndG/3rdG TKIs), nilotinib, dasatinib, bosutinib and ponatinib. Methods We identified a real-life cohort of 57 consecutive adult CML patients treated with 2ndG/3rdG TKI. All patients had a previous history of AOE. Ongoing use of secondary prevention of AOE (including antiplatelet agents, anticoagulant therapy, and statins) before starting a 2ndG/3rdG TKI was recorded, as well as CV risk factors. Results The 60-month cumulative incidence rate of recurrent AOEs was 47.8 ± 10.9%. Despite a history of AOE, 10 patients (16%) were not receiving secondary preventative measures. Patients treated with nilotinib and ponatinib showed a higher incidence of recurrent AOEs (76.7 ± 14.3% and 64 ± 20.1%, respectively) than those treated with dasatinib and bosutinib (44 ± 24.2% and 30.5 ± 15.5%, respectively) (p = 0.01). Only treatment with a 2ndG/3rdG TKI given as second or subsequent line therapy showed a significant association with an increased incidence of recurrent AOE (p = 0.039). Overall, 17 recurrent AOEs were observed; 3 CV-related deaths were reported. Conclusion CML patients with a previous history of AOE treated with 2ndG/3rdG TKI represent a particular patient population with a higher probability of experiencing a recurrent AOE; individualized treatment is needed to optimize secondary prevention.
Published: 2019

34. Outcome of very elderly chronic myeloid leukaemia patients treated with imatinib frontline

Author: Fabio Stagno, Patrizia Pregno, Alessandra Iurlo, Nicola Orofino, Gianfranco Giglio, Cristina Bucelli, Giovanna Mansueto, Massimiliano Bonifacio, Francesca Celesti, Elisabetta Abruzzese, Ester Orlandi, Antonella Russo-Rossi, Luigiana Luciano, Adam D'Addosio, Sara Galimberti, Dario Ferrero, Elena Crisà, Monica Crugnola, Gabriele Gugliotta, Enrico Montefusco, Gianantonio Rosti, Giovanna Rege Cambrin, Sergio Storti, Roberto Latagliata, Francesco Cavazzini, Fausto Castagnetti, Michele Cedrone, Mario Tiribelli, Endri Mauro, Antonella Gozzini, Gianni Binotto, Carmen Fava, Franca Falzetti, Mario Annunziata, Elisabetta Calistri, Romano Atelda, Federica Sorà, Nicola Sgherza, Isabella Capodanno, Sabina Russo, Malgorzata Monika Trawinska, Monica Bocchia, Massimo Breccia, Alessandro Isidori, Crugnola M., Castagnetti F., Breccia M., Ferrero D., Trawinska M.M., 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., Crisa E., Gugliotta G., Russo S., Cedrone M., RussoRossi A., Pregno P., Isidori A., Mauro E., Atelda R., Giglio G., Celesti F., Sora F., Storti S., D'Addosio A., Galimberti S., Orlandi E., Calistri E., Bocchia M., Cavazzini F., Rege Cambrin G., Orofino N., Luciano L., Sgherza N., Rosti G., Latagliata R., and Capodanno I.
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.drug_class, Socio-culturale, Tyrosine kinase inhibitor, Blastic Phase, Tyrosine-kinase inhibitor, Chronic myeloid leukaemia, Elderly, Outcome, Tyrosine kinase inhibitor, Chronic myeloid leukaemia, Elderly, Outcome, Disease-Free Survival, Follow-Up Studie, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, 80 and over, medicine, Humans, Chronic, Survival rate, Aged, Aged, 80 and over, Leukemia, Hematology, Settore MED/06 - ONCOLOGIA MEDICA, business.industry, Incidence (epidemiology), Imatinib, General Medicine, Survival Rate, Female, Follow-Up Studies, Imatinib Mesylate, 030220 oncology & carcinogenesis, Concomitant, Toxicity, BCR-ABL Positive, business, Myelogenous, 030215 immunology, medicine.drug, Human
Abstract: Very elderly (> 75years) 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 78.5years 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 45.0months, 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 ≤80years and > 80years, respectively (p = 0.098). Five years OS was 75.7% and 61.6% in patients ≤80years and > 80years, 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

35. Next-generation sequencing for BCR-ABL1 kinase domain mutation testing in patients with chronic myeloid leukemia: a position paper

Author: Sara Galimberti, Fabio Stagno, Patrizia Pregno, Monica Bocchia, Mario Tiribelli, Elisabetta Abruzzese, Giuseppe Saglio, Luigiana Luciano, Alessandra Iurlo, Gianantonio Rosti, Giovanni Barosi, Massimiliano Bonifacio, Massimo Breccia, Antonella Gozzini, Simona Soverini, Paolo Vigneri, Soverini S., Abruzzese E., Bocchia M., Bonifacio M., Galimberti S., Gozzini A., Iurlo A., Luciano L., Pregno P., Rosti G., Saglio G., Stagno F., Tiribelli M., Vigneri P., Barosi G., and Breccia M.
Subjects: Cancer Research, medicine.medical_specialty, Sanger sequencing, DNA Mutational Analysis, Fusion Proteins, bcr-abl, Computational biology, Review, lcsh:RC254-282, DNA sequencing, symbols.namesake, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Medicine, Humans, Molecular Biology, Protein Kinase Inhibitors, Hematology, business.industry, lcsh:RC633-647.5, Patient Selection, Chronic myeloid leukemia, Myeloid leukemia, High-Throughput Nucleotide Sequencing, BCR-ABL1 mutation, lcsh:Diseases of the blood and blood-forming organs, Protein-Tyrosine Kinases, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, Protein kinase domain, Mutation (genetic algorithm), Mutation, symbols, Mutation testing, Next-generation sequencing, Position paper, business
Abstract: BCR-ABL1 kinase domain (KD) mutation status is considered to be an important element of clinical decision algorithms for chronic myeloid leukemia (CML) patients who do not achieve an optimal response to tyrosine kinase inhibitors (TKIs). Conventional Sanger sequencing is the method currently recommended to test BCR-ABL1 KD mutations. However, Sanger sequencing has limited sensitivity and cannot always discriminate between polyclonal and compound mutations. The use of next-generation sequencing (NGS) is increasingly widespread in diagnostic laboratories and represents an attractive alternative. Currently available data on the clinical impact of NGS-based mutational testing in CML patients do not allow recommendations with a high grade of evidence to be prepared. This article reports the results of a group discussion among an ad hoc expert panel with the objective of producing recommendations on the appropriateness of clinical decisions about the indication for NGS, the performance characteristics of NGS platforms, and the therapeutic changes that could be applied based on the use of NGS in CML. Overall, these recommendations might be employed to inform clinicians about the practical use of NGS in CML.
Published: 2019

36. Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart

Author: Giovanni Caocci, Massimo Breccia, Ester Orlandi, Antonella Gozzini, Robin Foà, Luigiana Luciano, Nicola Sgherza, Francesco Albano, Sara Galimberti, Massimiliano Bonifacio, Elisabetta Abruzzese, Gabriele Gugliotta, Olga Mulas, Daniele Cattaneo, Gianni Binotto, Chiara Elena, Luigi Scaffidi, Claudia Baratè, Fabio Stagno, Patrizia Pregno, Immacolata Attolico, Fiorenza De Gregorio, Emilia Scalzulli, Fausto Castagnetti, Mario Annunziata, Giorgio La Nasa, Alessandra Iurlo, Francesca Pirillo, Malgorzata Monika Trawinska, Claudio Fozza, Caocci G., Mulas O., Abruzzese E., Luciano L., Iurlo A., Attolico I., Castagnetti F., Galimberti S., Sgherza N., Bonifacio M., Annunziata M., Gozzini A., Orlandi E.M., Stagno F., Binotto G., Pregno P., Fozza C., Trawinska M.M., De Gregorio F., Cattaneo D., Albano F., Gugliotta G., Barate C., Scaffidi L., Elena C., Pirillo F., Scalzulli E., La Nasa G., Foa R., and Breccia M.
Subjects: Male, Cancer Research, Decision Support Systems, Medical Oncology, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Retrospective Studie, Original Research Articles, Epidemiology, 80 and over, Medicine, Cumulative incidence, ponatinib, Original Research Article, arterial occlusive event, Chronic, Aged, 80 and over, Aspirin, Leukemia, Incidence (epidemiology), Incidence, Ponatinib, Imidazoles, Hematology, General Medicine, Middle Aged, Pyridazines, Treatment Outcome, Oncology, Italy, 030220 oncology & carcinogenesis, Hypertension, Female, prophylaxis, Pyridazine, medicine.drug, Human, Adult, medicine.medical_specialty, Chronic myeloid leukemia, Cardiology, 03 medical and health sciences, Clinical, Young Adult, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Risk factor, Imidazole, Retrospective Studies, Aged, business.industry, prophylaxi, Risk Factor, Coronary Occlusion, Decision Support Systems, Clinical, Retrospective cohort study, Blood pressure, chemistry, BCR-ABL Positive, business, 030215 immunology, Myelogenous
Abstract: Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 60-month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28months (range, 3-69months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P&nbsp
Published: 2019

37. Efficacy and safety of ruxolitinib and hydroxyurea combination in patients with hyperproliferative myelofibrosis

Author: Michele Cavo, Emilia Scalzulli, Francesca Palandri, Mario Tiribelli, Giovanni Caocci, Roberto Latagliata, Bruno Martino, Vincenzo Martinelli, Luigiana Luciano, Giulia Benevolo, Elena Rossi, Massimo Breccia, Valerio De Stefano, Robin Foà, Massimiliano Bonifacio, Novella Pugliese, Fabrizio Pane, Gianni Binotto, Breccia, Massimo, Luciano, Luigiana, Pugliese, Novella, Rossi, Elena, Tiribelli, Mario, Scalzulli, Emilia, Bonifacio, Massimiliano, Martino, Bruno, Latagliata, Roberto, Benevolo, Giulia, Caocci, Giovanni, Binotto, Gianni, Martinelli, Vincenzo, Cavo, Michele, Pane, Fabrizio, De Stefano, Valerio, Foà, Robin, Palandri, Francesca, Breccia, M., Luciano, L., Pugliese, N., Rossi, E., Tiribelli, M., Scalzulli, E., Bonifacio, M., Martino, B., Latagliata, R., Benevolo, G., Caocci, G., Binotto, G., Martinelli, V., Cavo, M., Pane, F., De Stefano, V., Foa, R., and Palandri, F.
Subjects: Male, Ruxolitinib, Myelofibrosis, Cell Count, Gastroenterology, Primary Myelofibrosi, 0302 clinical medicine, Retrospective Studie, 80 and over, Leukocytes, Hydroxyurea, Leukocytosis, Aged, 80 and over, Hematology, Myelofibrosi, General Medicine, Middle Aged, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Combination, Drug Therapy, Combination, Female, Survival Analysi, Patient Safety, medicine.symptom, Human, medicine.drug, Blood Platelets, medicine.medical_specialty, Efficacy, Aged, Cell Proliferation, Drug Administration Schedule, Humans, Primary Myelofibrosis, Pyrazoles, Retrospective Studies, Splenomegaly, Survival Analysis, Spleen, 03 medical and health sciences, Drug Therapy, Internal medicine, Nitriles, Myeloproliferation, medicine, Thrombocytosis, business.industry, Leukocyte, medicine.disease, Clinical trial, Settore MED/15 - MALATTIE DEL SANGUE, Pyrimidines, Pyrazole, Blood Platelet, business, 030215 immunology
Abstract: Ruxolitinib is the only commercially available JAK1/2 inhibitor approved for the treatment of myelofibrosis-related splenomegaly and symptoms. During treatment, as rare conditions, leukocytosis and/or thrombocytosis could develop and the management of these situations is not well established. We report here 53 myelofibrosis patients that received a combination of hydroxyurea and ruxolitinib because of uncontrolled myeloproliferation. Both drugs were administered outside clinical trials. At 48weeks, a significant reduction in leucocyte and platelet counts was observed (p= 0.02 and p= 0.04, respectively). Additionally, the spleen volume decreased from a median value of 10cm below the left costal margin (range, 0-10) to 6cm (range, 0-15). The rate of spleen response increased from 14% at the start of the combination to 45% after 48weeks. The safety profile of the combination was consistent with that observed with ruxolitinib single agent. These data require further confirmation in large cohorts of patients prospectively assessed.
Published: 2019

38. Differences in presenting features, outcome and prognostic models in patients with primary myelofibrosis and post-polycythemia vera and/or post-essential thrombocythemia myelofibrosis treated with ruxolitinib. New perspective of the MYSEC-PM in a large multicenter study

Author: Costanza Bosi, Franco Aversa, Elisabetta Abruzzese, Nicola Vianelli, Giulia Benevolo, G. Semenzato, Bruno Martino, Daniele Cattaneo, Adalberto Ibatici, Nicola Polverelli, Daniela Bartoletti, Nicola Sgherza, Massimiliano Bonifacio, Roberto Latagliata, Francesca Palandri, Francesco Di Raimondo, Francesco Cavazzini, Micaela Bergamaschi, Michele Cavo, Massimo Breccia, Mariella D'Adda, Alessandra Iurlo, Alessandro Isidori, Maria Letizia Bacchi Reggiani, Giuseppe A. Palumbo, Luigi Scaffidi, Alessia Tieghi, Gianni Binotto, Antonio Cuneo, Monica Crugnola, Francesco Soci, Roberto M. Lemoli, Mario Tiribelli, Lucia Catani, Giuseppe Auteri, Malgorzata Monika Trawinska, Florian H. Heidel, Domenico Penna, Domenico Russo, and Palandri F, Palumbo GA, Iurlo A, Polverelli N, Benevolo G, Breccia M, Abruzzese E, Tiribelli M, Bonifacio M, Tieghi A, Isidori A, Martino B, Sgherza N, D'Adda M, Bergamaschi M, Crugnola M, Cavazzini F, Bosi C, Binotto G, Auteri G, Latagliata R, Ibatici A, Scaffidi L, Penna D, Cattaneo D, Soci F, Trawinska M, Russo D, Cuneo A, Semenzato G, Di Raimondo F, Aversa F, Lemoli RM, Heidel F, Reggiani MLB, Bartoletti D, Cavo M, Catani L, Vianelli N.
Subjects: Ruxolitinib, medicine.medical_specialty, Anemia, Socio-culturale, Myelofibrosis, Gastroenterology, MYSEC-PM, Efficacy, 03 medical and health sciences, Essential, 0302 clinical medicine, Polycythemia vera, Internal medicine, Nitriles, Risk scores, Humans, Medicine, Thrombocythemia, Polycythemia Vera, Survival rate, Janus Kinases, business.industry, Essential thrombocythemia, IPSS, Myelofibrosi, Hematology, Prognosis, medicine.disease, Primary Myelofibrosis, Pyrazoles, Survival Rate, Thrombocythemia, Essential, Pyrimidines, International Prognostic Scoring System, 030220 oncology & carcinogenesis, Risk score, business, IPSS, MYSEC-PM, Myelofibrosis, Risk scores, Ruxolitinib, 030215 immunology, medicine.drug
Abstract: Recently, the myelofibrosis secondary to PV and ET prognostic model (MYSEC-PM) was introduced to assess prognosis in myelofibrosis (MF) secondary to polycythemia vera and essential thrombocythemia (post-PV and post-ET MF), replacing the International Prognostic Scoring System (IPSS) and/or Dynamic IPSS (DIPSS) that was applied for primary MF (PMF). In a cohort of 421 ruxolitinib (RUX)-treated patients (post-PV and post-ET MF: 44.2%), we evaluated the following: (1) disease phenotype, responses, and toxicity to RUX; and (2) performance of the MYSEC-PM in post-PV or post-ET ME. While the IPSS failed to correctly stratify post-PV or post-ET MF patients at diagnosis, the MYSEC-PM identified 4 risk categories projected at significantly different survival probability (P < .001). Additionally, the MYSEC-PM maintained a prognostic value in post-PV and post-ET MF also when used over time, at RUX start. Notably, the MYSEC-PM reclassified 41.8% and 13.6% of patients into a lower and higher risk category, respectively. Finally, patients at intermediate-1 risk had significantly higher spleen responses and lower hematological toxicities compared to higher risk patients. Compared to PMF, post-PV and post-ET MF presented a more hyperproliferative disease, with higher leukocyte and/or platelet count and hemoglobin levels both at diagnosis and at RUX start. Despite comparable response rates, post-PV and post-ET MF had lower rate of RUX-induced anemia and thrombocytopenia at 3 and 6 months. The study validates MYSEC-PM in post-PV and post-ET MF prognostication. Post-PV or post-ET MF represents a separate entity compared to PMF in terms of clinical manifestations and toxicity to RUX. (C) 2018 Elsevier Inc. All rights reserved.
Published: 2018

39. Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients

Author: Luigiana Luciano, Michele Cedrone, Daniele Vallisa, Francesco Cavazzini, Anna Guella, Massimo Breccia, P. Danise, Emilio Usala, Monica Crugnola, Paolo Avanzini, Fabio Stagno, Diamante Turri, Monica Bocchia, Patrizia Pregno, Gianni Binotto, Mario Tiribelli, Angelo Michele Carella, Ida Nardiello, E Orlandi, Alessandro Rambaldi, Marco Gobbi, Bruno Martino, Alessandra Iurlo, Gianluca Gaidano, Elisabetta Abruzzese, Simona Sica, Fabio Efficace, Carlo Gambacorti-Passerini, Esther Pungolino, Mario Annunziata, Massimiliano Bonifacio, Francesca Celesti, Giuliana Alimena, Antonella Gozzini, Breccia, M, Efficace, F, Sica, S, Abruzzese, E, Cedrone, M, Turri, D, Gobbi, M, Carella, A, Gozzini, A, Usala, E, Cavazzini, F, Danise, P, Tiribelli, M, Binotto, G, Pregno, P, Bocchia, M, Gaidano, G, Crugnola, M, Bonifacio, M, Avanzini, P, Celesti, F, Guella, A, Martino, B, Annunziata, M, Luciano, L, Stagno, F, Vallisa, D, Pungolino, E, Iurlo, A, Rambaldi, A, Nardiello, I, Orlandi, E, GAMBACORTI PASSERINI, C, and Alimena, G
Subjects: Myeloid, Male, Health Knowledge, Attitudes, Practice, Cancer Research, Quality of life, Surveys and Questionnaires, 80 and over, Medicine, Young adult, Survey, Aged, 80 and over, Practice, Leukemia, Hematology, Health Knowledge, Medicine (all), Chronic myeloid leukemia, Myeloid leukemia, Middle Aged, Protein-Tyrosine Kinases, Oncology, Leukemia, Myeloid, Chronic-Phase, Anxiety, Female, medicine.symptom, Adherence, Adolescent, Adult, Aged, Antineoplastic Agents, Humans, Medication Adherence, Protein Kinase Inhibitors, Quality of Life, Young Adult, medicine.medical_specialty, Socio-culturale, Therapeutic approach, Social support, Internal medicine, business.industry, Discontinuation, Attitudes, Physical therapy, Chronic-Phase, business
Abstract: Therapeutic approach for chronic myeloid leukemia (CML) patients has undergone a revolutionary change with the introduction of tyrosine kinase inhibitors, which improved overall survival and quality of life. Optimal therapy adherence has become of paramount importance to maximize the benefits in the long-term outcome. Several evidences have been reported that personal factors, such as social support, psychological and subjective perceptions about the drug used and the future, could influence adherence. We here report the results of a questionnaire specifically designed to evaluate factors influencing adherence and perceptions about the future, distributed to patients during regional Italian meetings. Overall, 1133 patients compiled the questionnaire: median age was 57 years. High rate of adherence was reported, but 42% of interviewed patients admitted that they had occasionally postponed a dose and 58% had discontinued therapy mainly for forgetfulness. The majority of patients discussed with personal physician about the importance of adherence and received sufficient information about illness and treatment, but would like to have discussed more about discomfort, anxiety and fear of the future. Summarizing personal drug compliance and estimating how many days a month, on average, the patients did not take the drug, the majority answered that it was less than 3 days (55%) and only a minority (4%) admitted that it was more than 7 days. Interviewed about discontinuation, 49% of patients answered that wouldn't interrupt because of fear of losing all the results achieved so far. This study suggests a higher level of satisfaction with more information received but the need of improving communication about possible future treatment free remission.
Published: 2015

40. Ultrasonographic endometrial monitoring during continuous-sequential hormonal replacement therapy regimen in postmenopausal women

Author: Carmine Nappi, Annalidia Sammartino, Marika Bonifacio, Pietro Affinito, Stefano Palomba, Affinito, P, Palomba, S, Sammartino, A, Bonifacio, M, and Nappi, Carmine
Subjects: medicine.medical_specialty, Hormone Replacement Therapy, medicine.drug_class, medicine.medical_treatment, HRT, Urology, Endometrium, Drug Administration Schedule, General Biochemistry, Genetics and Molecular Biology, Basal (phylogenetics), Predictive Value of Tests, medicine, Humans, endometrium, Ultrasonography, Gynecology, Chemotherapy, medicine.diagnostic_test, Progestogen, business.industry, Obstetrics and Gynecology, Middle Aged, medicine.disease, Menopause, Regimen, postmenopause, medicine.anatomical_structure, transvaginal ultrasonography, Estrogen, Female, business, Endometrial biopsy
Abstract: To evaluate the endometrial thickness in different periods of a continuous-sequential HRT regimen and to correlate the ultrasonographic findings with the histological patterns.The study was structured in two phases. In the 1st phase, 37 postmenopausal women (group A) treated by at least 6 months with a conventional continuous-sequential hormonal replacement therapy (cs-HRT) regimen were enrolled. In all patients, the endometrial thickness was measured at the 7th, 14th, 21st and 25th day of the cycle using transvaginal ultrasonography (TV-USG). In the 2nd phase of the study, other 41 postmenopausal women (group B) were enrolled and treated with the same sc-HRT regimen. At entry and after six cycles of cs-HRT, an endometrial biopsy was performed. The endometrial pattern was related with endometrial thickness. Either the evaluations were performed immediately after progestogen withdrawal bleeding, as showed by 1st phase results.The results of the 1st phase of the study showed a mean endometrial thickness significantly lower at 7th day of the cycle compared to 14th, 21st and 25th day (4.3+/-1.2 versus 6.6+/-2.9, 7.8+/-4.2 and 7.4+/-4.6 mm+/-SD, respectively). After six cycles of cs-HRT (2nd phase of the study), the mean endometrial thickness was significantly increased in comparison with basal values (4.2+/-1.5 versus 2.8+/-1.2 mm+/-SD; P0.05). Endometrial biopsies showed 13 cases (39.4%) of atrophy and 20 cases (60.6%) of proliferative endometrium. Mean endometrial thickness in case of atrophy was lower than in presence of a proliferative endometrium (3.7+/-1.2 versus 4.4+/-1.4 mm+/-SD; not significant). Endometrial thickness was4 mm in 16 cases (11 of atrophic and five of proliferative endometrium), between 4 and 5 mm in 15 cases (13 of proliferative and two of atrophic endometrium) and between 5 and 6 mm in two cases (either case of proliferative endometrium).The best timing for monitoring endometrial thickness during cs-HRT regimens is the period immediately after withdrawal bleeding improving the reliability of the ultrasonographic exam to identify endometrial pathologies.
Published: 2001

41. Effects of hormonal replacement therapy in postmenopausal hypertensive patients

Author: Raffaele Izzo, Pietro Affinito, Bruno Trimarco, Stefano Palomba, Marika Bonifacio, D. Fontana, Carmine Nappi, Affinito, P, Palomba, S, Bonifacio, M, Fontana, D, Izzo, R, Trimarco, Bruno, Nappi, Carmine, P., Affinito, S., Palomba, M., Bonifacio, D., Fontana, Izzo, Raffaele, and Nappi, C.
Subjects: medicine.medical_specialty, hypertension, medicine.medical_treatment, HRT, Adrenergic beta-Antagonists, Urology, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Sphygmomanometer, Medroxyprogesterone Acetate, Placebo, General Biochemistry, Genetics and Molecular Biology, law.invention, postmenopause, hormone replacement therapy, cardiovascular disease, Randomized controlled trial, law, medicine, Humans, Diuretics, Antihypertensive Agents, Triglycerides, Aged, Estradiol, business.industry, Estrogen Replacement Therapy, Obstetrics and Gynecology, Hormone replacement therapy (menopause), Blood Pressure Monitoring, Ambulatory, Middle Aged, Calcium Channel Blockers, medicine.disease, Circadian Rhythm, Surgery, Menopause, Regimen, Cholesterol, Blood pressure, Ambulatory, Female, business
Abstract: To evaluate the effect of hormonal replacement therapy (HRT) on blood pressure (BP) in postmenopausal hypertensive women.Sixty women affected by hypertension were enrolled and randomized in two groups of treatment: transdermal continuous HRT in a sequential regimen (group A) and placebo (group P). At baseline, after 3 and 6 months of treatment, the BP with standard sphygmomanometer and with 24-h ambulatory recording method was evaluated in two periods (from day 10 through day 16 of the cycle and from day 20 through day 27 of the cycle). At the same time, we also evaluated total cholesterol, LDL-c, HDL-c, triglycerides, and fibrinogen levels.After 3 and 6 months of treatment, no significant variations of systolic and diastolic BP measured with standard sphygmomanometer were detected in both groups. On the contrary, in group A in comparison with basal values and group P, and without difference between the two phases of treatment, the 24-h recording showed a significant (P0.05) decrease in BP. No significant variations were detected in group P versus baseline. In particular, we observed in group A at 3 months of treatment a significant (P0.05) decrease only in daytime BP in comparison with basal values and group P, without difference between the two phases of treatment. Indeed, the decrease in daytime BP was significant (P0.05) for both systolic and diastolic BP. At 3 and 6 months a significant (P0.05) decrease in total cholesterol, LDL-c and fibrinogen levels was detected in group A versus baseline and group P. HDL-c and triglyceride concentrations showed no significant variations.The transdermal HRT induces a significant reduction of BP values and a favorable metabolic action in postmenopausal hypertensive patients.
Published: 2001

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