Search

Your search keyword '"Pungolino E."' showing total 18 results
Start Over Author "Pungolino E." Topic humans
18 results on '"Pungolino E."'

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
Full Text
View/download PDF

2. Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias

Author

Porter, Jb, Lin, Kh, Beris, P, Forni, Gl, Taher, A, Habr, D, Domokos, G, Roubert, B, Thein, Sl, EPIC study investigators including Agaoglu, L, Alimena, G, Alonso, D, Ame, S, Angelucci, E, Arrizabalaga, B, Athanasiou Metaxa, M, Augustson, B, Aydinok, Y, Baba, A, Baccarani, M, Beck, J, Beyne Rauzy, O, Birgens, H, Bordessoule, D, Borgna Pignatti, C, Bosly, A, Bouabdallah, K, Bowen, D, Bron, D, Cappellini, Md, Capra, M, Cartron, G, Cazzola, M, Chalkias, C, Chan, Ll, Chancharunee, S, Chapman, C, Charoenkwan, P, Chasapopoulou, E, Cheze, S, Chuansumrit, A, Cianciulli, P, Dauriac, C, Delforge, M, Dölken, G, Dombret, H, Duyster, J, Economopoulos, T, Ehninger, G, Elalfy, M, El Beshlawy, A, Enggaard, L, Fenaux, P, Fillet, G, Filosa, A, Galanello, R, Ganser, A, Gastl, G, Gattermann, N, Giraudier, S, Goldfarb, A, Grigg, A, Guerci Bresler, A, Gumruk, F, Ha, Sy, Haase, D, Heinrich, B, Hertzberg, M, Ho, J, Hsu, Hc, Huang, S, Hunault Berger, M, Inusa, B, Jalumes, D, Jensen, J, Kattamis, A, Kilinc, Y, Kim, Kh, Kinsey, S, Kjeldsen, L, Koren, A, Lai, Me, Lai, Y, Lee, Jw, Lee, Kh, Lee, Sh, Legros, L, Li, C, Li, Ck, Li, Q, Linkesch, W, Lübbert, M, Lutz, D, Mohamed Thalha AJ, Mufti, G, Muus, P, Nobile, F, Ozsahin, H, Papadopoulos, N, Perrotta, S, Petrini, M, Pfeilstöcker, M, Piga, Antonio Giulio, Poole, J, Pungolino, E, Quarta, G, Ravoet, C, Remacha, Af, Rose, C, Roy, L, Saglio, Giuseppe, Sanz, G, Schmid, M, Schmugge, M, Schots, H, Secchi, G, Seymour, Jf, Shah, F, Shah, H, Shen, Z, Slama, B, Sutcharitchan, P, Tamary, H, Taylor, K, Tesch, Hj, Troncy, J, Vassilieff, D, Villegas, A, Viprakasit, V, Wainwright, L, Wassmann, B, Wettervald, M, Will, A, Wörmann, B, Wright, J, Yeh, Sp, Yoon, Ss, Zoumbos, Nc, Zweegman, S., Ozsahin, Ayse Hulya, Porter, Jb, Lin, Kh, Beris, P, Forni, Gl, Taher, A, Habr, D, Domokos, G, Roubert, B, Thein, Sl, on behalf of the EPIC study, Investigator, and Perrotta, Silverio

Subjects
safety, Male, Iron Overload, Adolescent, iron chelation therapy, Iron, Iron Chelating Agents/therapeutic use, Iron Chelating Agents, Benzoates, Anemia/drug therapy, Humans, Blood Transfusion, Benzoates/therapeutic use, Child, Iron/blood, ddc:616, ddc:618, iron overload, rare anaemias, serum ferritin, Ferritins/blood, Anemia, Original Articles, Triazoles, Deferasirox, Child, Preschool, Ferritins, rare anaemia, Female, Triazoles/therapeutic use
Abstract

Objectives: It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusiondependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. Methods: The efficacy and safety of deferasirox (Exjade) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10–30 mg⁄ kg ⁄ d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Results: Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells ⁄ kg ⁄ d), mean deferasirox dosing (19.3 vs. 19.0 mg⁄ kg ⁄ d) and baseline median serum ferritin (2926 vs. 2682 ng ⁄ mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng ⁄mL were attained, respectively ()26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (

Published
2011

3. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial

Author

Lee, Jw, Yoon, Ss, Shen, Zx, Ganser, A, Hsu, Hc, Habr, D, Domokos, G, Roubert, B, Porter, Jb, Agaoglu, L, Alimena, G, Alonso, D, Ame, S, Angelucci, E, Arrizabalaga, B, Athanasiou Metaxa, M, Augustson, B, Aydinok, Y, Baba, A, Baccarani, M, Beck, J, Beris, P, Beyne Rauzy, O, Birgens, H, Bordessoule, D, Borgna, Caterina, Bosly, A, Bouabdallah, K, Bowden, D, Bowen, D, Bron, D, Cappellini, Md, Capra, M, Cartron, G, Cazzola, M, Chalkias, C, Chan, Ll, Chancharunee, S, Chapman, C, Charoenkwan, P, Chasapopoulou, E, Cheze, S, Chuansumrit, A, Cianciulli, P, Dauriac, C, Delforge, M, Dölken, G, Dombret, H, Duyster, J, Economopoulos, T, Ehninger, G, Elalfy, M, El Beshlawy, A, Enggaard, L, Fenaux, P, Fillet, G, Filosa, A, Forni, G, Galanello, R, Gastl, G, Gattermann, N, Giraudier, S, Goldfarb, A, Grigg, A, Guerci Bresler, A, Gumruk, F, Ha, Sy, Haase, D, Heinrich, B, Hertzberg, M, Ho, J, Huang, S, Hunault Berger, M, Inusa, B, Jaulmes, D, Jensen, J, Kattamis, A, Kilinc, Y, Kim, Kh, Kinsey, S, Kjeldsen, L, Koren, A, Lai, Me, Lai, Y, Lee, Kh, Lee, Sh, Legros, L, Li, C, Li, Ck, Li, Q, Lin, Kh, Linkesch, W, Lübbert, M, Lutz, D, Mohamed Thalha AJ, Mufti, G, Muus, P, Nobile, F, Papadopoulos, N, Perrotta, S, Petrini, M, Pfeilstöcker, M, Piga, A, Poole, J, Pungolino, E, Quarta, G, Ravoet, C, Remacha, Af, Rose, C, Roy, L, Saglio, G, Sanz, G, Schmid, M, Schmugge, M, Schots, H, Secchi, G, Seymour, Jf, Shah, F, Shah, H, Shen, Z, Slama, B, Sutcharitchan, P, Taher, A, Tamary, H, Taylor, K, Tesch, Hj, Thein, Sl, Troncy, J, Vassilieff, D, Villegas, A, Viprakasit, V, Wainwright, L, Wassmann, B, Wettervald, M, Will, A, Wörmann, B, Wright, J, Yeh, Sp, Zoumbos, Nc, Zweegman, S., Lee, Jw, Yoon, S, Shen, Zx, Ganser, A, Hsu, Hc, Habr, D, Domokos, G, Roubert, B, Porter, Jb, EPIC study, Investigator, and Perrotta, Silverio

Subjects
Male, Biochemistry, Gastroenterology, Benzoates, beta-thalassemia, chemistry.chemical_compound, overloaded patients, oxidative stress, Prospective Studies, Prospective cohort study, pathophysiology, Beta thalassemia, complications, epidemiology, labile plasma iron, myelodysplastic syndromes, serum ferritin, transfusion-dependent anemias, Anemia, Aplastic, Hematology, Middle Aged, Tolerability, Creatinine, Iron chelation, Female, medicine.drug, Adult, medicine.medical_specialty, aplastic anemia, Adolescent, Anemia, Immunology, Iron Chelating Agents, Young Adult, Internal medicine, medicine, Humans, Aplastic anemia, therapy, business.industry, Myelodysplastic syndromes, Deferasirox, deferasirox, Cell Biology, Triazoles, medicine.disease, Chelation Therapy, Surgery, chemistry, Ferritins, business
Abstract

The prospective 1-year Evaluation of Patients' Iron Chelation with Exjade (EPIC) study enrolled a large cohort of 116 patients with aplastic anemia; the present analyses evaluated the efficacy and safety of deferasirox in this patient population. After 1 year, median serum ferritin decreased significantly from 3254 ng/mL at baseline to 1854 ng/mL (P < .001). Decreases occurred in chelation-naive (3229-1520 ng/mL; P < .001, last-observation-carried-forward analysis), and previously chelated (3263-2585 ng/mL; P = .21, last-observation-carried-forward analysis) patients and were reflective of dose adjustments and ongoing iron intake. Baseline labile plasma iron levels were within normal range despite high serum ferritin levels. The most common drug-related adverse events were nausea (22%) and diarrhea (16%). Serum creatinine increases more than 33% above baseline and the upper limit of normal occurred in 29 patients (25%), but there were no progressive increases; concomitant use of cyclosporine had a significant impact on serum creatinine levels. The decrease in mean alanine aminotransferase levels at 1 year correlated significantly with reduction in serum ferritin (r = 0.40, P < .001). Mean absolute neutrophil and platelet counts remained stable during treatment, and there were no drug-related cytopenias. This prospective dataset confirms the efficacy and well characterizes the tolerability profile of deferasirox in a large population of patients with aplastic anemia. This study was registered at www.clinicaltrials.gov as #NCT00171821.

Published
2010

4. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

Author

Gattermann, N., Finelli, C., Porta, M. D., Fenaux, P., Ganser, A., Guerci Bresler, A., Schmid, M., Taylor, K., Vassilieff, D., Habr, D., Domokos, G., Roubert, B., Rose, C., Agaoglu, L., Alimena, G., Alonso, D., Ame, S., Angelucci, E., Businco, A., Arrizabalaga, B., Athanasiou Metaxa, M., Augustson, B., Aydinok, Y., Baba, A., Baccarani, M., Beck, J., Beris, P., Beyne Rauzy, O., Birgens, H., Bordessoule, D., Borgna, Caterina, Bosly, A., Bouabdallah, K., Bowden, D., Bowen, D., Bron, D., Cappellini, M. D., Capra, M., Cartron, G., Cazzola, M., Chalkias, C., Chan, L. L., Chancharunee, S., Chapman, C., Charoenkwan, P., Chasapopoulou, E., Cheze, S., Chuansumrit, A., Cianciulli, P., Dauriac, C., Delforge, M., Dölken, G., Dombret, H., Duyster, J., Economopoulos, T., Ehninger, G., Elalfy, M., El Beshlawy, A., Enggaard, L., Fillet, G., Filosa, A., Forni, G., Galanello, R., Gastl, G., Giraudier, S., Goldfarb, A., Grigg, A., Gumruk, F., S. Y., Ha, Haase, D., Heinrich, B., Hertzberg, M., Ho, J., Hsu, H. C., Huang, S., Hunault Berger, M., Inusa, B., Jaulmes, D., Jensen, J., Kattamis, A., Kilinc, Y., Kim, K. H., Kinsey, S., Kjeldsen, L., Koren, A., Lai, M. E., Lai, Y., Lee, J. W., Lee, K. H., Lee, S. H., Legros, L., Li, C., C. K., Li, Li, Q., Lin, K. H., Linkesch, W., Lübbert, M., Lutz, D., Mohamed Thalha, A. J., Mufti, G., Muus, P., Nobile, F., Papadopoulos, N., Perrotta, S., Petrini, M., Pfeilstöcker, M., Piga, A., Poole, J., Porter, J. B., Pungolino, E., Quarta, G., Ravoet, C., Jolimont Lobbes, H. H., Remacha, A. F., Roy, L., Saglio, G., Sanz, G., Schmugge, M., Schots, H., Secchi, G., Seymour, J. F., Shah, F., Shah, H., Shen, Z., Slama, B., Sutcharitchan, P., Taher, A., Tamary, H., Tesch, H. J., Thein, S. L., Troncy, J., Villegas, A., Viprakasit, V., Wainwright, L., Wassmann, B., Wettervald, M., Will, A., Wörmann, B., Wright, J., Yeh, S. P., Yoon, S. S., Zoumbos, N. S., Zweegman, S., Gattermann, N, Finelli, C, Porta, Md, Fenaux, P, Ganser, A, GUERCI BRESLER, A, Schmid, M, Taylor, K, Vassilieff, D, Habr, D, Domokos, G, Roubert, B, Rose, C, EPIC study, Investigator, Perrotta, Silverio, Gattermann N, Finelli C, Porta MD, Fenaux P, Ganser A, Guerci-Bresler A, Schmid M, Taylor K, Vassilieff D, Habr D, Domokos G, Roubert B, Rose C, Baccarani M, EPIC study investigators., and Çukurova Üniversitesi

Subjects
Male, Pediatrics, Cancer Research, Blood transfusion, Thalassemia, medicine.medical_treatment, Gastroenterology, Benzoates, Child, Hematology, biology, Benzoic Acids, Alanine Transaminase, Adolescent, Adult, Aged, Blood Transfusion, Preschool, Female, Ferritins, Humans, Iron Chelating Agents, Iron Overload, Middle Aged, Myelodysplastic Syndromes, Triazoles, Young Adult, Oncology, Child, Preschool, medicine.drug, medicine.medical_specialty, Myelodysplastic syndromes, deferasirox, iron chelation therapy, labile plasma iron, myelodysplastic syndromes, serum ferritin, Serum ferritin, Deferasirox, Iron chelation therapy, Labile plasma iron, Internal medicine, medicine, Adverse effect, iron-overloaded patients, transfusion, Labile plasmairon, business.industry, medicine.disease, Discontinuation, Iron chelationtherapy, Alanine transaminase, biology.protein, business, Myelodysplastic syndrome
Abstract

PubMedID: 20451251 The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500. ng/mL, ~50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p

Published
2010

5. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias

Author

Cappellini, M. D., Porter, J., El Beshlawy, A., C. K., Li, Seymour, J. F., Elalfy, M., Gattermann, N., Giraudier, S., Lee, J. W., Chan, L. L., Lin, K. H., Rose, C., Taher, A., Thein, S. L., Viprakasit, V., Habr, D., Domokos, G., Roubert, B., Kattamis, A., Agaoglu, L., Alimena, G., Alonso, D., Ame, S., Angelucci, E., Businco, A., Arrizabalaga, B., Athanasiou Metaxa, M., Augustson, B., Aydinok, Y., Baba, A., Baccarani, M., Beck, J., Beris, P., Beyne Rauzy, O., Birgens, H., Bordessoule, D., Borgna, Caterina, Bosly, A., Bouabdallah, K., Bowden, D., Bowen, D., Bron, D., Capra, M., Cartron, G., Cazzola, M., Chalkias, C., Chancharunee, S., Chapman, C., Charoenkwan, P., Chasapopoulou, E., Cheze, S., Chuansumrit, A., Cianciulli, P., Dauriac, C., Delforge, M., Dölken, G., Dombret, H., Duyster, J., Economopoulos, T., Ehninger, G., Enggaard, L., Fillet, G., Filosa, A., Forni, G., Galanello, R., Gastl, G., Goldfarb, A., Grigg, A., Gumruk, F., S. Y., Ha, Haase, D., Heinrich, B., Hertzberg, M., Ho, J., Hsu, H. C., Huang, S., Hunault Berger, M., Inusa, B., Jaulmes, D., Jensen, J., Kilinc, Y., Kim, K. H., Kinsey, S., Kjeldsen, L., Koren, A., Lai, M. E., Lai, Y., Lee, K. H., Lee, S. H., Legros, L., Li, C., Li, Q., Linkesch, W., Lübbert, M., Lutz, D., Mohamed Thalha, A. J., Mufti, G., Muus, P., Nobile, F., Papadopoulos, N., Perrotta, S., Petrini, M., Pfeilstöcker, M., Piga, A., Poole, J., Porter, J. B., Pungolino, E., Quarta, G., Ravoet, C., Jolimont Lobbes, H. H., Remacha, A. F., Roy, L., Saglio, G., Sanz, G., Schmugge, M., Schots, H., Secchi, G., Shah, F., Shah, H., Shen, Z., Slama, B., Sutcharitchan, P., Tamary, H., Tesch, H. J., Troncy, J., Villegas, A., Wainwright, L., Wassmann, B., Wettervald, M., Will, A., Wörmann, B., Wright, J., Yeh, S. P., Yoon, S. S., Zoumbos, N. S., and Zweegman, S.

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Blood transfusion, Iron Overload, Adolescent, Anemia, Thalassemia, medicine.medical_treatment, Iron chelation therapy, Transfusion medicine, Transfusion-dependent anemias, Hemosiderosis, Iron Chelating Agents, Gastroenterology, Benzoates, Young Adult, IRON CHELATION, Internal medicine, medicine, Humans, Blood Transfusion, Tissue Distribution, SERUM FERRITIN, Chelation therapy, Prospective Studies, Child, Aged, Aged, 80 and over, business.industry, Myelodysplastic syndromes, Deferasirox, Hematology, Middle Aged, Triazoles, medicine.disease, DEFERASOROX, Deferoxamine, Child, Preschool, Ferritins, Female, Original Article, business, TRANSFUSION-DEPENDENT ANEMIAS, Iron, Dietary, medicine.drug
Abstract

Background Following a clinical evaluation of deferasirox (Exjade) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (agedor=2 years) with transfusional hemosiderosis from various types of anemia.The recommended initial dose was 20 mg/kg/day for patients receiving 2-4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline.The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (-264 ng/mL; P0.0001), reflecting dosage adjustments and ongoing iron intake. The most common (5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%). Conclusions Analysis of this large, prospectively collected data set confirms the response to chelation therapy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821).

Published
2009

6. Clinical utility of the absolute number of circulating CD34-positive cells in patients with chronic myeloproliferative disorders

Author

Passamonti, F., Vanelli, L., Malabarba, L., Rumi, E., Pungolino, E., LUCA MALCOVATI, Pascutto, C., Morra, E., Lazzarino, M., and Cazzola, M.

Subjects
Adult, Aged, 80 and over, Male, Myeloproliferative Disorders, Adolescent, Antigens, CD34, Cell Count, Essential thrombocythemia, Middle Aged, Hematopoietic Stem Cells, Cross-Sectional Studies, Primary Myelofibrosis, polycythemia myelofibrosis, CD34, Humans, Female, Longitudinal Studies, Prospective Studies, Polycythemia Vera, Biomarkers, Aged, Thrombocythemia, Essential
Abstract

Flow cytometry enumeration of peripheral blood CD34-positive cells provides reliable measurements of circulating hematopoietic progenitors in humans. Since the absolute number of circulating CD34-positive cells has been previously found to be elevated in myelofibrosis with myeloid metaplasia (MMM), we prospectively studied the clinical utility of this parameter in the work-up of patients with chronic myeloproliferative disorders.Of the 248 consecutive patients enrolled in this study, 106 had polycythemia vera (PV), 90 essential thrombocythemia (ET), and 52 myelofibrosis with myeloid metaplasia (MMM). The study population included both newly diagnosed and established cases, and of these latter some patients were on cytoreductive treatment while others were chemotherapy naive. Both cross-sectional and longitudinal investigations were carried out. Flow cytometry enumeration of CD34-positive cells was performed using a single-platform assay.Median numbers and ranges of circulating CD34-positive cells were 2.3x10(6)/L (0-5) in 20 control subjects, 2.2x10(6)/L (0-14) in those with PV, 2.4x10(6)/L (0-14) in those with ET, and 114x10(6)/L (6-2,520) in MMM patients. Analysis of variance demonstrated that values were markedly higher in MMM patients than in the remaining groups, and counts did not appear to fluctuate over short periods of follow-up. In both cross-sectional and longitudinal investigations on patients at clinical onset and/or out of cytoreductive treatment, a CD34-positive count ofor = 15x10(6)/L was always associated with MMM, clearly indicating a disease-related specificity.The absolute number of circulating CD34-positive cells is normal or anyhow lower than 15x10(6)/L in patients with uncomplicated PV or ET, whereas it is equal or above this cut-off in those with MMM, likely reflecting abnormal hematopoietic progenitor cell trafficking. Thus, enumeration of circulating CD34-positive cells may be useful in the work-up of patients with myeloproliferative disorders.

7. 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

8. Nilotinib-induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study

Author

Michela Anghilieri, Marianna Caramella, Alessandra Trojani, Gabriella De Canal, Salvatore Artale, Alessandra Iurlo, Francesca Lunghi, Maria Luisa Latargia, Michele Nichelatti, Barbara Di Camillo, Alessandra Perego, Chiara Elena, Ester Pungolino, Alfredo Molteni, Francesco Spina, Giacomo Baruzzo, Mariella D'Adda, Maria Cristina Carraro, Mauro Turrini, Roberto Cairoli, Lorenza Borin, Pungolino, E, D'Adda, M, De Canal, G, Trojani, A, Perego, A, Elena, C, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Artale, S, Anghilieri, M, Molteni, A, Caramella, M, Baruzzo, G, Nichelatti, M, Di Camillo, B, and Cairoli, R

Subjects
Male, Oncology, CD34, Cell Cycle Proteins, Biomarkers, Pharmacological, NF-KappaB Inhibitor alpha, MED/15 - MALATTIE DEL SANGUE, Bone Marrow, Recurrence, Granulocyte Colony-Stimulating Factor, Philadelphia Chromosome, Prospective Studies, NFKBIA, Aged, 80 and over, Gene Expression Regulation, Leukemic, Myeloid leukemia, Hematology, General Medicine, Middle Aged, Intercellular Adhesion Molecule-1, GEP, medicine.anatomical_structure, Neoplastic Stem Cells, Female, Stem cell, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Chronic Myeloid Leukemia, Antineoplastic Agents, stem cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, Protein Kinase Inhibitors, nilotinib, Aged, business.industry, Gene Expression Profiling, Imatinib, Janus Kinase 2, Discontinuation, stem cell, Gene expression profiling, Pyrimidines, Nilotinib, Case-Control Studies, ATP-Binding Cassette Transporters, Bone marrow, business
Abstract

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph-chromosome and the BCR-ABL tyrosine-kinase (TK). Target-therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second-generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin−Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in-vivo activity and timecourse of first-line Nilotinib therapy on BM CD34+/lin−Ph+ cells clearance. Eighty-seven CP-CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin− cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per-Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin− cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK-STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.

Published
2021

9. Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment

Author

Salvatore Artale, Gabriella De Canal, Enrica Morra, Maria Cristina Carraro, Giuseppe Rossi, Simona Malato, Alessandra Perego, Maria Luisa Latargia, Mariella D'Adda, Francesco Lanza, Ester Orlandi, Francesco Spina, Barbara Di Camillo, Alessandra Iurlo, Mauro Turrini, Michela Anghilieri, Roberto Cairoli, Milena Lodola, Alessandra Trojani, Lorenza Borin, Ester Pungolino, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, and Cairoli, R

Subjects
Myeloid, 0301 basic medicine, Cancer Research, Time Factors, CD34, Antigens, CD34, Transcriptome, Leukocyte Count, 0302 clinical medicine, hemic and lymphatic diseases, CML, Leukemic, Leukemia, Gene Expression Regulation, Leukemic, Myeloid leukemia, General Medicine, Protein-Tyrosine Kinases, GEP, Treatment Outcome, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Leukemia, Myeloid, Chronic-Phase, bone marrow CD34+/lin-cell, medicine.drug, bone marrow CD34+/lin-cells, Bone Marrow Cells, NO, 03 medical and health sciences, Genetics, medicine, Humans, Antigens, nilotinib, business.industry, Gene Expression Profiling, medicine.disease, Gene expression profiling, Pyrimidines, 030104 developmental biology, Gene Expression Regulation, Nilotinib, Cancer research, Chronic-Phase, Bone marrow, business
Abstract

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib.

Published
2017
Full Text
View/download PDF

10. Increased tumor burden in patients with chronic myeloid leukemia after 36 months of imatinib discontinuation

Author

Silvia Mori, Bruno Martino, Sarit Assouline, Micaela Bergamaschi, Eros Di Bona, Marcio Andrade-Campos, Chiara Elena, Patrizia Crivori, Ester Pungolino, Alessandra Iurlo, Antonella Gozzini, Philipp le Coutre, Elisa Diral, Elisabetta Abruzzese, Laura Antolini, Alessandra Pirola, Diletta Fontana, Fabio Stagno, Maria Luisa Bonanomi, Rocco Piazza, Carmen Fava, Carlo Gambacorti-Passerini, Jessica Petiti, Diral, E, Mori, S, Antolini, L, Abruzzese, E, Le Coutre, P, Martino, B, Pungolino, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Gozzini, A, Andrade-Campos, M, Stagno, F, Iurlo, A, Pirola, A, Fontana, D, Petiti, J, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, and Gambacorti Passerini, C

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Adolescent, Immunology, Tumor burden, Antineoplastic Agents, Biochemistry, Young Adult, chronic myeloid leukemia, MED/15 - MALATTIE DEL SANGUE, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Recurrence free survival, Internal medicine, medicine, Humans, In patient, Aged, Aged, 80 and over, business.industry, Myeloid leukemia, Imatinib, clinical trial, Cell Biology, Hematology, Middle Aged, Prognosis, BCR-ABL protein, Tumor Burden, Discontinuation, Survival Rate, Withholding Treatment, Imatinib Mesylate, Female, business, Follow-Up Studies, Cohort study, medicine.drug, discontinuation
Abstract

TO THE EDITOR: The Imatinib Suspension and Validation (ISAV) study1 is a multicenter trial of imatinib discontinuation (ID) among patients with chronic myeloid leukemia (CML) in undetectable deep molecular remission (U-DMR). After 12 months of follow-up, 48% of patients relapsed (total n = 107), with the majority of relapses occurring within the first 9 months. An inverse relationship between patient age and risk of relapse was also observed at this timepoint. Here we report the final results of ISAV after a median follow-up of 49 months, as well as the dynamics of leukemic tumor load as determined by digital polymerase chain reaction (dPCR) in nonrelapsed patients. This trial is registered at www.clinicaltrials.gov (NCT01578213). Eligible patients were 18 years and older and had CML, either in chronic or accelerated phase, with U-DMR of at least 18 months’ duration and at least...

Published
2020

11. Nilotinib induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-chronic myeloid leukemia

Author

Roberto Cairoli, Alessandra Perego, Lorenza Borin, Francesco Spina, Giuseppe Rossi, Alessandra Trojani, Alessandra Iurlo, Silvia Cantoni, Michela Anghilieri, Maria Cristina Carraro, Maria Luisa Latargia, Gabriella De Canal, Ester Pungolino, Pierangelo Spedini, Mauro Turrini, Ester Orlandi, Salvatore Artale, Mariella D'Adda, Enrica Morra, Barbara Di Camillo, Milena Lodola, Francesca Lunghi, Pungolino, E, Rossi, G, De Canal, G, Trojani, A, D'Adda, M, Perego, A, Orlandi, E, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Lodola, M, Artale, S, Anghilieri, M, Spedini, P, Cantoni, S, Di Camillo, B, Morra, E, and Cairoli, R

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, CD34, Protein Kinase Inhibitor, Antigens, CD34, Bone Marrow Cells, Cell Count, Newly diagnosed, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Prospective Studies, Protein Kinase Inhibitors, Aged, Aged, 80 and over, Hematology, business.industry, Myeloid leukemia, Middle Aged, Prospective Studie, 030104 developmental biology, medicine.anatomical_structure, Pyrimidines, Pyrimidine, Nilotinib, 030220 oncology & carcinogenesis, Cancer research, Neoplastic Stem Cells, Bone Marrow Cell, Female, Neoplastic Stem Cell, Bone marrow, business, Human, medicine.drug
Published
2018

12. Personal history and quality of life in chronic myeloid leukemia patients: a cross-sectional study using narrative medicine and quantitative analysis

Author

Guendalina Graffigna, Alessandro Maggi, Fabio Efficace, Sara Galimberti, Lucia Mastrullo, Roberta Della Seta, Tamara Intermesoli, Matteo Pacilli, Silvana Capalbo, Ester Pungolino, Michele Pizzuti, Chiara Elena, Margherita Maffioli, Massimo Breccia, Enrico Capochiani, Nicola Di Renzo, Giuliana Alimena, Davide Rapezzi, Alessandro Melosi, Elena Trabacchi, Carlo Gambacorti-Passerini, Mario Luppi, Federico Simonetti, Daniele Vallisa, Franca Falzetti, Ester Orlandi, Alessandra Iurlo, Breccia, M, Graffigna, G, Galimberti, S, Iurlo, A, Pungolino, E, Pizzuti, M, Maggi, A, Falzetti, F, Capalbo, S, Intermesoli, T, Maffioli, M, Elena, C, Melosi, A, Simonetti, F, Capochiani, E, Seta, R, Pacilli, M, Luppi, M, Di Renzo, N, Mastrullo, L, Trabacchi, E, Vallisa, D, Rapezzi, D, Orlandi, E, GAMBACORTI PASSERINI, C, Efficace, F, and Alimena, G

Subjects
Adult, Male, medicine.medical_specialty, Cross-sectional study, Pain medicine, Population, Tyrosine kinase inhibitor, Settore M-PSI/06 - PSICOLOGIA DEL LAVORO E DELLE ORGANIZZAZIONI, Disease, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Chronic myeloid leukemia, Narrative medicine, Tyrosine kinase inhibitors, Oncology, Medicine, Humans, Psychiatry, education, Protein Kinase Inhibitors, Aged, Aged, 80 and over, education.field_of_study, Narration, business.industry, Nursing research, Myeloid leukemia, Middle Aged, Cross-Sectional Studies, Evaluation Studies as Topic, 030220 oncology & carcinogenesis, Quality of Life, Female, business, 030215 immunology
Abstract

Background: Tyrosine kinase inhibitors (TKIs) drastically changed the outcome of patients diagnosed with chronic myeloid leukemia (CML). Several reports indicated the advantage of continue long-term adherence associated with positive outcome. Therefore, it is important to better understand from the patient’s standpoint the experience of living with the disease and the related treatment. Objectives: In this study, quantitative analysis and narrative medicine were combined to get insights on this issue in a population of 257 patients with CML in chronic phase treated with TKIs (43 % men, with a median age of 58 years, 27 % aged 31–50 years), followed for a median time of 5 years. Sixty-one percent of patients enrolled were treated in first line, whereas 37 % were treated in second line. Results: The results showed more positive perceptions and acceptance in males compared to females, without impact of disease on relationships. Level of positive acceptance was more evident in elderly compared to younger patients, with a close connection with median time from diagnosis. Overall, female patients reported negative perceptions and an impact of disease on family daily living. The majority of patients understood the importance of continue adherence to treatment, with 27 % resulting less adherent (60 % for forgetfulness), even if well informed and supported by his/her physician. Discussion and conclusions: Narrative medicine, in association to quantitative analysis, can help physicians to understand needs of their patients in order to improve communication.

Published
2016

13. Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

Author

Silvia, Mori, Elisabetta, Vagge, Philipp, le Coutre, Elisabetta, Abruzzese, Bruno, Martino, Ester, Pungolino, Chiara, Elena, Ivana, Pierri, Sarit, Assouline, Anna, D'Emilio, Antonella, Gozzini, Pilar, Giraldo, Fabio, Stagno, Alessandra, Iurlo, Michela, Luciani, Giulia, De Riso, Sara, Redaelli, Dong-Wook, Kim, Alessandra, Pirola, Caterina, Mezzatesta, Anna, Petroccione, Agnese, Lodolo D'Oria, Patrizia, Crivori, Rocco, Piazza, Carlo, Gambacorti-Passerini, Mori, S, Vagge, E, Le Coutre, P, Abruzzese, E, Martino, B, Pungolino, E, Elena, C, Pierri, I, Assouline, S, D'Emilio, A, Gozzini, A, Giraldo, P, Stagno, F, Iurlo, A, Luciani, M, De Riso, G, Redaelli, S, Kim, D, Pirola, A, Mezzatesta, C, Petroccione, A, Lodolo D'Oria, A, Crivori, P, Piazza, R, and GAMBACORTI PASSERINI, C

Subjects
Adult, Male, Leukemia, Reverse Transcriptase Polymerase Chain Reaction, bcr-abl, Fusion Proteins, bcr-abl, Age Factors, Fusion Proteins, Hematology, Middle Aged, Predictive Value of Tests, Recurrence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Imatinib Mesylate, Humans, Female, BCR-ABL Positive, Aged, Follow-Up Studies, Chronic, Myelogenous
Abstract

Imatinib is effective for the treatment of chronic myeloid leukemia (CML). However even undetectable BCR-ABL1 by Q-RT-PCR does not equate to eradication of the disease. Digital-PCR (dPCR), able to detect 1 BCR-ABL1 positive cell out of 10(7) , has been recently developed. The ISAV study is a multicentre trial aimed at validating dPCR to predict relapses after imatinib discontinuation in CML patients with undetectable Q-RT-PCR. CML patients under imatinib therapy since more than 2 years and with undetectable PCR for at least 18 months were eligible. Patients were monitored by standard Q-RT-PCR for 36 months. Patients losing molecular remission (two consecutive positive Q-RT-PCR with at least 1 BCR-ABL1/ABL1 value above 0.1%) resumed imatinib. The study enrolled 112 patients, with a median follow-up of 21.6 months. Fifty-two of the 108 evaluable patients (48.1%), relapsed; 73.1% relapsed in the first 9 months but 14 late relapses were observed between 10 and 22 months. Among the 56 not-relapsed patients, 40 (37.0% of total) regained Q-RT-PCR positivity but never lost MMR. dPCR results showed a significant negative predictive value ratio of 1.115 [95% CI: 1.013-1.227]. An inverse relationship between patients age and risk of relapse was evident: 95% of patients45 years relapsed versus 42% in the class ≥45 to65 years and 33% of patients ≥65 years [P(χ(2) ) 0.0001]. Relapse rates ranged between 100% (45 years, dPCR+) and 36% (45 years, dPCR-). Imatinib can be safely discontinued in the setting of continued PCR negativity; age and dPCR results can predict relapse.

Published
2015

14. Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment

Author

Anna D'Emilio, Diamante Turri, Sabina Russo, Tamara Intermesoli, Simona Soverini, Bruno Mario Cesana, Nicoletta Testoni, Monia Lunghi, M. Bergamaschi, Valeria Cancelli, Massimo Breccia, Domenico Russo, A. De Vivo, Emilio Usala, Valeria Santini, Mariella Girasoli, Bruno Martino, Michele Malagola, Antonella Russo-Rossi, Simona Bernardi, Monica Bocchia, Ester Pungolino, Giovanni Martinelli, Michele Baccarani, Catia Bigazzi, Elisabetta Abruzzese, Mario Tiribelli, Fabio Stagno, Giovanna Rege Cambrin, G Nicolini, R. Di Lorenzo, A Di Palma, Patrizia Pregno, Giovanni Rosti, Miriam Fogli, Fausto Castagnetti, Cristina Skert, Russo, D, Malagola, M., Skert, C., Cancelli, V., Turri, D., Pregno, P., Bergamaschi, M., Fogli, M., Testoni, N., De Vivo, A., Castagnetti, F., Pungolino, E., Stagno, F., Breccia, M., Martino, B., Intermesoli, T., Cambrin, G.R., Nicolini, G., Abruzzese, E., Tiribelli, M., Bigazzi, C., Usala, E., Russo, S., Russo-Rossi, A., Lunghi, M., Bocchia, M., D'Emilio, A., Santini, V., Girasoli, M., Di Lorenzo, R., Bernardi, S., Di Palma, A., Cesana, B.M., Soverini, S., Martinelli, G., Rosti, G., and Baccarani, M.

Subjects
Male, medicine.medical_specialty, Chronic Myeloid Leukemia, Antineoplastic Agents, Pilot Projects, Kaplan-Meier Estimate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, hemic and lymphatic diseases, medicine, Humans, In Situ Hybridization, Fluorescence, Aged, Aged, 80 and over, Hematology, business.industry, Remission Induction, Imatinib, medicine.disease, Confidence interval, Surgery, Clinical trial, Leukemia, Regimen, Imatinib mesylate, Oncology, Female, Imatinib Mesylate, Molecular Response, Original Article, business, medicine.drug
Abstract

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35–59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

Published
2015

15. 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

16. Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia

Author

Domenico, Russo, Giovanni, Martinelli, Michele, Malagola, Cristina, Skert, Simona, Soverini, Ilaria, Iacobucci, Antonio, De Vivo, Nicoletta, Testoni, Fausto, Castagnetti, Gabriele, Gugliotta, Diamante, Turri, Micaela, Bergamaschi, Michela, Bergamaschi, Patrizia, Pregno, Ester, Pungolino, Fabio, Stagno, Massimo, Breccia, Bruno, Martino, Tamara, Intermesoli, Carmen, Fava, Elisabetta, Abruzzese, Mario, Tiribelli, Catia, Bigazzi, Bruno Mario, Cesana, Gianantonio, Rosti, Michele, Baccarani, Russo D, Martinelli G, Malagola M, Skert C, Soverini S, Iacobucci I, De Vivo A, Testoni N, Castagnetti F, Gugliotta G, Turri D, Bergamaschi M, Pregno P, Pungolino E, Stagno F, Breccia M, Martino B, Intermesoli T, Fava C, Abruzzese E, Tiribelli M, Bigazzi C, Cesana BM, Rosti G, and Baccarani M.

Subjects
Oncology, Male, EUROPEAN-LEUKEMIANET, bcr-abl, Fusion Proteins, bcr-abl, PHILADELPHIA-CHROMOSOME, Imatinib treatment, Biochemistry, Piperazines, Remission induction, TARGETED THERAPY, hemic and lymphatic diseases, 80 and over, Chronic, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Aged, 80 and over, Hematology, Leukemia, Health Policy, Remission Induction, Myeloid leukemia, Survival Rate, Treatment Outcome, Benzamides, Cytogenetic Analysis, Aged, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Protein Kinase Inhibitors, Pyrimidines, Cell Biology, Immunology, medicine.drug, medicine.medical_specialty, Internal medicine, medicine, TYROSINE KINASE INHIBITORS, neoplasms, Survival rate, business.industry, Fusion Proteins, Imatinib, Alternative treatment, Imatinib mesylate, BCR-ABL Positive, business, Myelogenous
Abstract

We report a study of an alternative treatment schedule of imatinib (IM) in chronic myeloid leukemia (CML). Seventy-six Philadelphia-positive (Ph+), BCR-ABL-positive patients aged 65 years or older who had been treated with IM for more than 2 years and who were in stable complete cytogenetic response (CCgR) and major molecular response (MMR) were enrolled in a single-arm study to test the effects of a policy of intermittent IM (INTERIM) therapy for 1 month on and 1 month off. With a minimum follow-up of 4 years, 13 patients (17%) lost CCgR and MMR and 14 (18%) lost MMR only. All these patients resumed continuous IM and all but one (lost to follow-up) regained CCgR and MMR. No patients progressed to accelerated or blastic phase or developed clonal chromosomal abnormalities in Ph+ cells or BCR-ABL mutations. In elderly Ph+ CML patients carefully selected for a stable CCgR (lasting >2 years), the policy of INTERIM treatment affected the markers of residual disease, but not the clinical outcomes (overall and progression-free survival). This trial was registered at www.clinicaltrials.gov as NCT 00858806.

Published
2013

17. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up

Author

Francesca Palandri, Fausto Castagnetti, Nicoletta Testoni, Simona Luatti, Giulia Marzocchi, Simona Bassi, Massimo Breccia, Giuliana Alimena, Ester Pungolino, Giovanna Rege Cambrin, Riccardo Varaldo, Maurizio Miglino, Giorgina Specchia, Eliana Zuffa, Felicetto Ferrara, Monica Bocchia, Giuseppe Saglio, Daniele Alberti, Giovanni Martinelli, Michele Baccarani, Gianantonio Rosti, G. I. M., PANE, FABRIZIO, Francesca, Palandri, Fausto, Castagnetti, Nicoletta, Testoni, Simona, Luatti, Giulia, Marzocchi, Simona, Bassi, Massimo, Breccia, Giuliana, Alimena, Ester, Pungolino, Giovanna Rege, Cambrin, Riccardo, Varaldo, Maurizio, Miglino, Giorgina, Specchia, Eliana, Zuffa, Felicetto, Ferrara, Monica, Bocchia, Giuseppe, Saglio, Pane, Fabrizio, Daniele, Alberti, Giovanni, Martinelli, Michele, Baccarani, Gianantonio, Rosti, G. I., M., Palandri F, Castagnetti F, Testoni N, Luatti S, Marzocchi G, Bassi S, Breccia M, Alimena G, Pungolino E, Rege-Cambrin G, Varaldo R, Miglino M, Specchia G, Zuffa E, Ferrara F, Bocchia M, Saglio G, Pane F, Alberti D, Martinelli G, Baccarani M, Rosti G, and GIMEMA Working Party on Chronic Myeloid Leukemia

Subjects
Adult, Male, medicine.medical_specialty, Myeloid, Time Factors, Adolescent, Gastroenterology, Piperazines, Young Adult, chronic myeloid leukemia, hemic and lymphatic diseases, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Transplantation, Homologous, chronic myeloid leukemia, blast crisis, imatinib, outcome, long-term, Survival rate, Letter to the Editor, Aged, Aged, 80 and over, long-term, business.industry, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Imatinib, Hematology, Middle Aged, medicine.disease, Surgery, Survival Rate, Leukemia, Imatinib mesylate, medicine.anatomical_structure, Pyrimidines, Treatment Outcome, imatinib, Benzamides, outcome, Imatinib Mesylate, Female, business, Blast Crisis, Complete Hematologic Response, medicine.drug, Chronic myelogenous leukemia, Follow-Up Studies
Abstract

Background Imatinib mesylate is the first line treatment for chronic myeloid leukemia. In patients with advanced phase of the disease, the advent of imatinib significantly increased survival. However, few long-term data, based on large, prospective and controlled trials are available on the outcome of these patients. Design and Methods We conducted a phase II trial of imatinib 600 mg daily in patients with chronic myeloid leukemia in blast crisis. The return to chronic phase was defined as

Published
2008

18. Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H

Author

Alessandra Tedeschi, Anna Maria Cafro, Roberto Cairoli, Valentina Rossi, Barbara Scarpati, L. Intropido, Marco Montillo, R Farioli, Giovanna D'Avanzo, Bruno Brando, Ester Pungolino, S Veronese, Enrica Morra, Montillo, M, Tedeschi, A, Rossi, V, Cairoli, R, Pungolino, E, Intropido, L, Cafro, A, D'Avanzo, G, Farioli, R, Brando, B, Scarpati, B, Veronese, S, and Morra, E

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Time Factors, Antibodies, Neoplasm, medicine.medical_treatment, Chronic lymphocytic leukemia, Antigens, CD34, Hematopoietic stem cell transplantation, Ara-C, Antibodies, Monoclonal, Humanized, Transplantation, Autologous, Campath-1H, Fludarabine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, Leukocytes, Humans, Medicine, Alemtuzumab, Hematopoietic Stem Cell Mobilization, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, Hematology, Middle Aged, Hematopoietic Stem Cells, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Transplantation, Leukemia, Immunology, Female, business, Vidarabine, medicine.drug
Abstract

Chronic lymphocytic leukemia (CLL) cells could be undetectable by flow cytometry or polymerase chain reaction after sequential treatment with fludarabine and Campath-1H. Concern has been raised regarding the ability to mobilize sufficient peripheral blood progenitor cells (PBPCs) for autografting after purine analogues, and there are few data about PBPC collection after Campath-1H. In all, 16 CLL patients responding to sequential chemo-immunotherapy entered the study. In 10, mobilization regimen consisted of granulocyte colony-stimulating factor (G-CSF) 5-10 microg/kg/die. Patients failing mobilization or not achieving the target of 2.5 x 10(6) CD34+ cells/kg underwent a second attempt using intermediate-dose (ID) Ara-C, 800 mg/m(2) every 12 h for six doses+G-CSF. PBPC collection after G-CSF alone was successful in two out of 10 patients. An adequate number of CD34+ cells were collected after ID Ara-C+G-CSF in eight patients failing the mobilization with G-CSF alone and in five out of six who did not receive G-CSF before. Greater yields of PBPCs were collected with Ara-C+G-CSF compared with G-CSF alone (13.8 vs 3.3). The extrahematologic toxicity was manageable. In conclusion, PBPC collection is feasible in CLL patients treated with sequential therapy including fludarabine and Campath-1H. Excellent yields were obtained in 92.8% of patients primed with ID Ara-C+G-CSF.

Published
2004

Catalog

Books, media, physical & digital resources
See catalog results