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17 results on '"GIMEMA CML Working Party"'

1. Nilotinib for the frontline treatment of Ph+ chronic myeloid leukemia

Author

Rosti, Gianantonio, Palandri, Francesca, Castagnetti, Fausto, Breccia, Massimo, Levato, Luciano, Gugliotta, Gabriele, Capucci, Adele, Cedrone, Michele, Fava, Carmen, Intermesoli, Tamara, Cambrin, Giovanna Rege, Stagno, Fabio, Tiribelli, Mario, Amabile, Marilina, Luatti, Simona, Poerio, Angela, Soverini, Simona, Testoni, Nicoletta, Martinelli, Giovanni, Alimena, Giuliana, Pane, Fabrizio, Saglio, Giuseppe, Baccarani, Michele, and GIMEMA CML Working Party

Published
2009
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2. Results of high-dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase 2 trial of the GIMEMA CML Working Party

Author

Castagnetti, Fausto, Palandri, Francesca, Amabile, Marilina, Testoni, Nicoletta, Luatti, Simona, Soverini, Simona, Iacobucci, Ilaria, Breccia, Massimo, Rege Cambrin, Giovanna, Stagno, Fabio, Specchia, Giorgina, Galieni, Piero, Iuliano, Franco, Pane, Fabrizio, Saglio, Giuseppe, Alimena, Giuliana, Martinelli, Giovanni, Baccarani, Michele, Rosti, Gianantonio, and for the GIMEMA CML Working Party

Published
2009
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3. Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients

Author

Castagnetti, Fausto, Breccia, Massimo, Gugliotta, Gabriele, Martino, Bruno, D’Adda, Mariella, Stagno, Fabio, Carella, Angelo Michele, Avanzini, Paolo, Tiribelli, Mario, Trabacchi, Elena, Visani, Giuseppe, Gobbi, Marco, Salvucci, Marzia, Levato, Luciano, Binotto, Gianni, Capalbo, Silvana Franca, Bochicchio, Maria Teresa, Soverini, Simona, Cavo, Michele, Martinelli, Giovanni, Alimena, Giuliana, Pane, Fabrizio, Saglio, Giuseppe, Rosti, Gianantonio, Baccarani, Michele, GIMEMA CML Working Party, Bocchia, Monica, Castagnetti, Fausto, Breccia, Massimo, Gugliotta, Gabriele, Martino, Bruno, D'Adda, Mariella, Stagno, Fabio, Carella, Angelo Michele, Avanzini, Paolo, Tiribelli, Mario, Trabacchi, Elena, Visani, Giuseppe, Gobbi, Marco, Salvucci, Marzia, Levato, Luciano, Binotto, Gianni, Capalbo, Silvana Franca, Bochicchio, Maria Teresa, Soverini, Simona, Cavo, Michele, Martinelli, Giovanni, Alimena, Giuliana, Pane, Fabrizio, Saglio, Giuseppe, Rosti, Gianantonio, Baccarani, Michele, Breccia, M, Martino, B, D'Adda, M, Stagno, F, Carella, Am, Avanzini, P, Tiribelli, M, Trabacchi, E, Visani, G, Gobbi, M, Salvucci, M, Levato, L, Binotto, G, Capalbo, Sf, Bochicchio, MARIA TERESA, Alimena, G, Pane, F, and Saglio, G

Subjects
Blood Glucose, Myeloid, Male, 030204 cardiovascular system & hematology, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, 80 and over, Chronic Myelogenous Leukemia, Aged, 80 and over, Leukemia, Hematology, Incidence (epidemiology), Remission Induction, Myeloid leukemia, Articles, Middle Aged, Cholesterol, Treatment Outcome, 030220 oncology & carcinogenesis, Leukemia, Myeloid, Chronic-Phase, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Molecular response, Young Adult, 03 medical and health sciences, Aged, Humans, Protein Kinase Inhibitors, Pyrimidines, Thrombosis, Triglycerides, chronic myeloid leukemia, Internal medicine, medicine, Adverse effect, Tyrosine kinase inhibitors, business.industry, Nilotinib, Discontinuation, Surgery, chemistry, Arterial Thrombosi, Chronic-Phase, Glycated hemoglobin, business
Abstract

The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR4.0) and 17% (MR4.5) of patients at 2 years; 58% of the enrolled patients achieved a MR4.0 at least once, with a sustained MR4.0 in 52% of them. With a median observation of 29 months (range 24–37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391).

Published
2016
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4. 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

5. 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

6. Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon- : 5-year outcome

Author

Palandri, Francesca, Iacobucci, Ilaria, Castagnetti, Fausto, Testoni, Nicoletta, Poerio, Angela, Amabile, Marilina, Breccia, Massimo, Intermesoli, Tamara, Iuliano, Francesco, Rege Cambrin, Giovanna, Tiribelli, Mario, Miglino, Maurizio, Pane, Fabrizio, Saglio, Giuseppe, Martinelli, Giovanni, Rosti, Gianantonio, Baccarani, Michele, GIMEMA CML Working Party, Bocchia, Monica, Palandri F, Iacobucci I, Castagnetti F, Testoni N, Poerio A, Amabile M, Breccia M, Intermesoli T, Iuliano F, Rege-Cambrin G, Tiribelli M, Miglino M, Pane F, Saglio G, Martinelli G, Rosti G, Baccarani M, GIMEMA Working Party on CML., Francesca, Palandri, Ilaria, Iacobucci, Fausto, Castagnetti, Nicoletta, Testoni, Angela, Poerio, Marilina, Amabile, Massimo, Breccia, Tamara, Intermesoli, Francesco, Iuliano, Giovanna Rege, Cambrin, Mario, Tiribelli, Maurizio, Miglino, Pane, Fabrizio, Giuseppe, Saglio, Giovanni, Martinelli, Gianantonio, Rosti, Michele, Baccarani, and G. I., M.

Subjects
Oncology, medicine.medical_specialty, Time Factors, Phases of clinical research, Alpha interferon, IMATINIB, Disease-Free Survival, Piperazines, Cohort Studies, Chronic myeloid leukemia, Imatinib, Interferon-alpha, Long-term results, Antineoplastic Combined Chemotherapy Protocols, Benzamides, Cytogenetics, Follow-Up Studies, Humans, Imatinib Mesylate, Immunologic Factors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Patient Compliance, Pyrimidines, Treatment Outcome, Hematology, Pegylated interferon, Internal medicine, medicine, Chronic, Interferon alfa, CHRONIC MYELOID LEUKEMIA, Leukemia, business.industry, Myeloid leukemia, medicine.disease, Imatinib mesylate, Immunology, BCR-ABL Positive, business, Myelogenous, medicine.drug, Chronic myelogenous leukemia
Abstract

In 2004, we reported the short-term results of a multicentric, phase 2 study of imatinib 400 mg daily and pegylated interferon-alpha in the treatment of 76 early chronic phase Philadelphia-positive chronic myeloid leukemia patients. In this report, we update the results with an observation time of five years. After two years of treatment, all but 10 patients (13%) had discontinued pegylated interferon-alpha. The complete cytogenetic response rate at five years was 87%, and 94% of complete cytogenetic responders maintained the complete cytogenetic response after five years. All but one complete cytogenetic response also achieved a major molecular response. These data confirm the excellent response to imatinib front-line and the stability of the complete cytogenetic response. Any possible additional benefit of the combination with interferon-alpha remains uncertain, due to low patient compliance.

Published
2008
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7. Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis

Author

Luatti, Simona, Castagnetti, Fausto, Marzocchi, Giulia, Baldazzi, Carmen, Gugliotta, Gabriele, Iacobucci, Ilaria, Specchia, Giorgina, Zanatta, Lucia, Rege Cambrin, Giovanna, Mancini, Marco, Abruzzese, Elisabetta, Zaccaria, Alfonso, Grimoldi, Maria Grazia, Gozzetti, Alessandro, Ameli, Gaia, Capucci, Maria Adele, Palka, Giandomenico, Bernasconi, Paolo, Palandri, Francesca, Pane, Fabrizio, Saglio, Giuseppe, Martinelli, Giovanni, Rosti, Gianantonio, Baccarani, Michele, Testoni, Nicoletta, GIMEMA CML Working Party, Bocchia, Monica, S Luatti, F Castagnetti, G Marzocchi, C Baldazzi, G Gugliotta, I Iacobucci, G Specchia, L Zanatta, G Rege-Cambrin, M Mancini, E Abruzzese, A Zaccaria, M G Grimoldi, A Gozzetti, G Ameli, M A Capucci, G Palka, P Bernasconi, F Palandri, F Pane, G Saglio, G Martinelli, G Rosti, M Baccarani, N Testoni, and on behalf of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Working Party on CML

Subjects
Oncology, Myeloid, Male, Messenger, Biochemistry, Piperazines, Additional chromosomal abnormalities (ACA), European LeukemiaNet, hemic and lymphatic diseases, 80 and over, Medicine, Philadelphia Chromosome, Prospective Studies, Prospective cohort study, In Situ Hybridization, Fluorescence, In Situ Hybridization, Aged, 80 and over, Leukemia, Reverse Transcriptase Polymerase Chain Reaction, Hematology, Middle Aged, Prognosis, Survival Rate, medicine.anatomical_structure, Leukemia, Myeloid, Chronic-Phase, Benzamides, Cytogenetic Analysis, Imatinib Mesylate, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Antineoplastic Agents, Philadelphia chromosome, Real-Time Polymerase Chain Reaction, IMATINIB, Fluorescence, Young Adult, Internal medicine, Humans, RNA, Messenger, Survival rate, Aged, Chromosome Aberrations, business.industry, Imatinib, Cell Biology, PHILADELPHIA-POSITIVE LEUKEMIAS, medicine.disease, Pyrimidines, eye diseases, stomatognathic diseases, Imatinib mesylate, RNA, Chronic-Phase, business, CHRONIC MYELOID LEUKEMIA (CML)
Abstract

Additional chromosomal abnormalities (ACAs) in Philadelphia-positive cells have been reported in ∼ 5% of patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). Few studies addressing the prognostic significance of baseline ACAs in patients treated with imatinib have been published previously. The European LeukemiaNet recommendations suggest that the presence of ACAs at diagnosis is a “warning” for patients in early CP, but there is not much information about their outcome after therapy with tyrosine kinase inhibitors. To investigate the role of ACAs in early CP CML patients treated with imatinib mesylate, we performed an analysis in a large series of 559 patients enrolled in 3 prospective trials of the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on CML: 378 patients were evaluable and ACAs occurred in 21 patients (5.6%). The overall cytogenetic and molecular response rates were significantly lower and the time to response was significantly longer in patients with ACAs. The long-term outcome of patients with ACAs was inferior, but the differences were not significant. The prognostic significance of each specific cytogenetic abnormality was not assessable. Therefore, we confirm that ACAs constitute an adverse prognostic factor in CML patients treated with imatinib as frontline therapy. This study was registered with clinicaltrials.gov as NCT00514488 and NCT00510926.

Published
2012

8. THE BCR-ABL FUSION TRANSCRIPT HAS A PROGNOSTIC IMPACT IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH IMATINIB IN EARLY CHRONIC PHASE: A GIMEMA CML WP ANALYSIS

Author

Castagnetti, F, Gugliotta, G, Palandri, F, Breccia, M, Specchia, G, Abruzzese, E, Levato, L, Cavazzini, F, Orlandi, E, Stagno, F, Di Lorenzo, R, Annunziata, M, Usala, E, Sica, S, Galieni, P, Rege-Cambrin, G, Amabile, M, Soverini, S, Testoni, N, Alimena, G, Martinelli, G, Pane, F, Saglio, G, Baccarani, M, and Rosti, G for the GIMEMA CML Working Party

Published
2011

9. Variant Philadelphia translocations: molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA WP on CML analysis

Author

Marzocchi, Giulia, Castagnetti, Fausto, Luatti, Simona, Baldazzi, Carmen, Stacchini, Monica, Gugliotta, Gabriele, Amabile, Marilina, Specchia, Giorgina, Sessarego, Mario, Giussani, Ursula, Valori, Laura, Discepoli, Giancarlo, Montaldi, Anna, Santoro, Alessandra, Bonaldi, Laura, Giudici, Giovanni, Cianciulli, Anna Maria, Giacobbi, Francesca, Palandri, Francesca, Pane, Fabrizio, Saglio, Giuseppe, Martinelli, Giovanni, Baccarani, Michele, Rosti, Gianantonio, Testoni, Nicoletta, GIMEMA CML Working Party, Bocchia, Monica, Marzocchi, G, Castagnetti, F, Luatti, S, Baldazzi, C, Stacchini, M, Gugliotta, G, Amabile, M, Specchia, G, Sessarego, M, Giussani, U, Valori, L, Discepoli, G, Montaldi, A, Santoro, A, Bonaldi, L, Giudici, G, Cianciulli, Am, Giacobbi, F, Palandri, F, Pane, Fabrizio, Saglio, G, Martinelli, G, Baccarani, M, Rosti, G, Testoni, N, Gruppo Italiano Malattie EMatologiche dell'Adulto Working Party on Chronic Myeloid, Leukemia, Marzocchi G., Castagnetti F., Luatti S., Baldazzi C., Stacchini M., Gugliotta G., Amabile M., Specchia G., Sessarego M., Giussani U., Valori L., Discepoli G., Montaldi A., Santoro A., Bonaldi L., Giudici G., Cianciulli A.M., Giacobbi F., Palandri F., Pane F., Saglio G., Martinelli G., Baccarani M., Rosti G., and Testoni N.

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Adolescent, Immunology, Chromosomal translocation, Imatinib therapy, Biology, Biochemistry, Piperazines, Young Adult, European LeukemiaNet, diagnosis/drug therapy/genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Internal medicine, 80 and over, medicine, Humans, Philadelphia Chromosome, Chronic, Aged, Aged, 80 and over, Leukemia, medicine.diagnostic_test, Myeloid leukemia, Imatinib, Cell Biology, Hematology, Middle Aged, Prognosis, Survival Analysis, Pyrimidines, Imatinib mesylate, Adolescent, Adult, Aged, Aged, 80 and over, Cytogenetic Analysis, Female, Humans, Leukemia, Myelogenous, BCR-ABL Positive, diagnosis/drug therapy/genetics, Male, Middle Aged, Philadelphia Chromosome, Piperazines, therapeutic use, Prognosis, Pyrimidines, therapeutic use, Survival Analysis, Young Adult, therapeutic use, Benzamides, Cytogenetic Analysis, Female, Imatinib Mesylate, CHRONIC MYELOID LEUKEMIA (CML), Tyrosine kinase, Fluorescence in situ hybridization, medicine.drug
Abstract

Variant Philadelphia (Ph) chromosome translocations have been reported in 5%-10% of patients with newly diagnosed chronic myeloid leukemia (CML). Variant translocations may involve one or more chromosomes in addition to 9 and 22, and can be generated by 2 different mechanisms, 1-step and 2-step rearrangements, as revealed by fluorescence in situ hybridization. The prognostic significance of the occurrence of variant translocations has been discussed in previous studies. The European LeukemiaNet recommendations do not provide a “warning” for patients with variant translocations, but there is limited information about their outcome after therapy with tyrosine kinase inhibitors. To identify the role of variant translocations in early chronic phase (CP) CML patients treated with imatinib mesylate, we performed an analysis in a large series of 559 patients enrolled in 3 prospective imatinib trials of the Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Working Party on CML. Variant translocations occurred in 30 patients (5%). Our data show that the presence of variant translocations has no impact on the cytogenetic and molecular response or on outcome, regardless of the involvement of different mechanisms, the number of involved chromosomes, or the presence of deletions. Therefore, we suggest that patients with variant translocations do not constitute a “warning” category in the imatinib era. This study is registered at www.clinicaltrials.gov as NCT00514488 and NCT00510926.

Published
2011

10. Deletions of the derivative chromosome 9 do not influence the response and the outcome of chronic myeloid leukemia in early chronic phase treated with imatinib mesylate: GIMEMA CML Working Party analysis

Author

Castagnetti, Fausto, Testoni, Nicoletta, Luatti, Simona, Marzocchi, Giulia, Mancini, Marco, Kerim, Simonetta, Giugliano, Emilia, Albano, Francesco, Cuneo, Antonio, Abruzzese, Elisabetta, Martino, Bruno, Palandri, Francesca, Amabile, Marilina, Iacobucci, Ilaria, Alimena, Giuliana, Pane, Fabrizio, Martinelli, Giovanni, Saglio, Giuseppe, Baccarani, Michele, Rosti, Gianantonio, GIMEMA CML working party, Bocchia, Monica, Castagnetti, F., Testoni, N., Luatti, S., Marzocchi, G., Mancini, M., Kerim, S., Giugliano, E., Albano, F., Cuneo, A., Abruzzese, E., Martino, B., Palandri, F., Amabile, M., Iacobucci, I., Alimena, G., Pane, Fabrizio, Martinelli, G., Saglio, G., Baccarani, M., Rosti, G., Castagnetti F, Testoni N, Luatti S, Marzocchi G, Mancini M, Kerim S, Giugliano E, Albano F, Cuneo A, Abruzzese E, Martino B, Palandri F, Amabile M, Iacobucci I, Alimena G, Pane F, Martinelli G, Saglio G, Baccarani M, Rosti G, Castagnetti, F, Testoni, N, Luatti, S, Marzocchi, G, Mancini, M, Kerim, S, Giugliano, E, Albano, F, Cuneo, A, Abruzzese, E, Martino, B, Palandri, F, Amabile, M, Iacobucci, I, Alimena, G, Martinelli, G, Saglio, G, and Baccarani, M

Subjects
Oncology, poor-prognosis, Myeloid, Male, Cancer Research, Kaplan-Meier Estimate, Severity of Illness Index, Piperazines, European LeukemiaNet, fusion gene transcripts, Reference Values, hemic and lymphatic diseases, 80 and over, Prospective Studies, stem-cell transplantation, In Situ Hybridization, In Situ Hybridization, Fluorescence, Aged, 80 and over, Adolescent, Adult, Age Factors, Aged, Benzamides, Chromosomes, Human, Pair 9, Cytogenetic Analysis, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Imatinib Mesylate, Italy, Leukemia, Myeloid, Chronic-Phase, Logistic Models, Maximum Tolerated Dose, Middle Aged, Multivariate Analysis, Probability, Prognosis, Pyrimidines, Reverse Transcriptase Polymerase Chain Reaction, Risk Assessment, Statistics, Nonparametric, Survival Analysis, Treatment Outcome, Young Adult, Gene Deletion, Medicine (all), Leukemia, philadelphia-chromosome, Statistics, Myeloid leukemia, chronic myelogenous leukemia, medicine.anatomical_structure, abl tyrosine kinase, bcr expression, cytogenetic responses, minimal-residual-disease, patients receiving imatinib, Drug, medicine.drug, Human, Pair 9, medicine.medical_specialty, Derivative chromosome, Chromosomes, Fluorescence, Dose-Response Relationship, chronic myeloid leukemia, Internal medicine, medicine, Nonparametric, business.industry, Imatinib, medicine.disease, Imatinib mesylate, Immunology, Chronic-Phase, Bone marrow, business
Abstract

Purpose Deletions of the derivative chromosome 9 [der(9)] have been associated with a poor prognosis in chronic myeloid leukemia (CML) across different treatment modalities. In the imatinib era, the prognostic impact of der(9) deletions has been evaluated mainly in patients with late chronic-phase (CP) CML, giving partially conflicting results. Few data are available in the early CP setting. For this reason, in 2006, the European LeukemiaNet recommendations still considered der(9) deletions as a candidate adverse prognostic factor and required a careful monitoring of the patient. Patients and Methods To investigate the prognostic value of der(9) deletions in early CP CML, we performed an analysis of three prospective imatinib trials of the Italian Group for Hematological Malignancies of the Adult (GIMEMA) CML Working Party. Results A fluorescent in situ hybridization (FISH) analysis of bone marrow cells was performed at diagnosis; der(9) deletions were detected in 60 (12%) of 521 evaluable patients. At 60 months, the cumulative incidence of complete cytogenetic response and major molecular response—and the probability of event-free survival, failure-free survival, progression-free survival, and overall survival—in patients with and without deletions were not statistically different. Conclusion Our data strongly support the notion that, when investigated by FISH, der(9) deletions are not a poor prognostic factor in patients with early CP CML treated with imatinib.

Published
2010

11. Long-term outcome of complete cytogenetic responders after imatinib 400 mg in late chronic phase, philadelphia-positive chronic myeloid leukemia: the GIMEMA Working Party on CML

Author

Palandri, Francesca, Iacobucci, Ilaria, Martinelli, Giovanni, Amabile, Marilina, Poerio, Angela, Testoni, Nicoletta, Soverini, Simona, Castagnetti, Fausto, De Vivo, Antonio, Breccia, Massimo, Specchia, Giorgina, Abruzzese, Elisabetta, Martino, Bruno, Cilloni, Daniela, Saglio, Giuseppe, Pane, Fabrizio, Liberati, Anna Marina, Rosti, Gianantonio, Baccarani, Michele, GIMEMA CML Working Party, Bocchia, Monica, Francesca, Palandri, Ilaria, Iacobucci, Giovanni, Martinelli, Marilina, Amabile, Angela, Poerio, Nicoletta, Testoni, Simona, Soverini, Fausto, Castagnetti, Antonio De, Vivo, Massimo, Breccia, Giorgina, Specchia, Elisabetta, Abruzzese, Bruno, Martino, Daniela, Cilloni, Giuseppe, Saglio, Pane, Fabrizio, Anna Marina, Liberati, Gianantonio, Rosti, Michele, Baccarani, G. I., M., Palandri F, Iacobucci I, Martinelli G, Amabile M, Poerio A, Testoni N, Soverini S, Castagnetti F, De Vivo A, Breccia M, Specchia G, Abruzzese E, Martino B, Cilloni D, Saglio G, Pane F, Liberati AM, Rosti G, Baccarani M, and GIMEMA Working Party on CML.

Subjects
Male, Cancer Research, Time Factors, Messenger, Drug Resistance, Fusion Proteins, bcr-abl, Gastroenterology, Piperazines, 80 and over, FAILURE, Prospective Studies, RNA, Neoplasm, Chronic, Prospective cohort study, Proto-Oncogene Proteins c-abl, BCR-ABL, MOLECULAR RESPONSE, Aged, 80 and over, Leukemia, CHRONIC MYELOGENOUS LEUKEMIA, Myeloid leukemia, Middle Aged, Prognosis, Survival Rate, Treatment Outcome, Oncology, Cohort, Benzamides, Proto-Oncogene Proteins c-bcr, Imatinib Mesylate, Female, medicine.drug, MESYLATE THERAPY, FOLLOW-UP, INTERFERON-ALPHA, SURVIVAL BENEFIT, BLAST CRISIS, MANAGEMENT, Adult, medicine.medical_specialty, Alpha interferon, Antineoplastic Agents, Aged, Drug Resistance, Neoplasm, Humans, Interferon-alpha, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Pyrimidines, RNA, Messenger, COMPLETE CYTOGENETIC RESPONDERS (CCR), Internal medicine, medicine, IMATINIB MESYLATE (IM), Survival rate, business.industry, LATE CHRONIC PHASE (LCP), Fusion Proteins, Imatinib, medicine.disease, Surgery, Imatinib mesylate, Neoplasm, RNA, BCR-ABL Positive, business, Chronic myelogenous leukemia, Myelogenous
Abstract

Purpose Imatinib mesylate (IM) has rapidly become the front-line treatment of Philadelphia-positive (Ph-pos) chronic myeloid leukemia, but the number of patients who were treated and are being treated with IM second-line is still substantial. Patients and Methods We have monitored and analyzed the cytogenetic and molecular response to IM 400 mg/d in a cohort of 277 late chronic phase (LCP) patients who were resistant or intolerant to interferon-α and were observed for 48 to 79 months (median, 72 months). Results One hundred fifty-three patients (55%) achieved a complete cytogenetic response (CCgR). Seventy-seven percent of them were still in CCgR after 5 years. The rate of response loss did not increase over time. The 6-year progression-free survival and overall survival of these 153 complete cytogenetic responders were 90% and 91%, respectively. Molecular response was less than major in 21%, major in 78%, and complete in one patient only. Conclusion These data confirm that, in LCP the CCgR rate to IM is 50% to 60%, and show that CCgR is stable and is associated with a prolonged survival, even if leukemia continues to be molecularly detectable.

Published
2008

12. Impact of age on the outcome of patients with chronic myeloid leukemia in late chronic phase: results of a phase II study of the GIMEMA CML Working Party

Author

Rosti, Gianantonio, Iacobucci, Ilaria, Bassi, Simona, Castagnetti, Fausto, Amabile, Marilina, Cilloni, Daniela, Poerio, Angela, Soverini, Simona, Palandri, Francesca, Rege Cambrin, Giovanna, Iuliano, Franco, Alimena, Giuliana, Latagliata, Roberto, Testoni, Nicoletta, Pane, Fabrizio, Saglio, Giuseppe, Baccarani, Michele, Martinelli, Giovanni, GIMEMA CML Working Party, Bocchia, Monica, Rosti G, Iacobucci I, Bassi S, Castagnetti F, Amabile M, Cilloni D, Poerio A, Soverini S, Palandri F, Rege Cambrin G, Iuliano F, Alimena G, Latagliata R, Testoni N, Pane F, Saglio G, Baccarani M, Martinelli G., Rosti, G, Iacobucci, I, Bassi, S, Castagnetti, F, Amabile, M, Cilloni, D, Poerio, A, Soverini, S, Palandri, F, REGE CAMBRIN, G, Iuliano, F, Alimena, G, Latagliata, R, Testoni, N, Pane, Fabrizio, Saglio, G, Baccarani, M, and Martinelli, G.

Subjects
Adult, Male, medicine.medical_specialty, Aging, Adolescent, Phases of clinical research, Antineoplastic Agents, Disease-Free Survival, Piperazines, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, medicine, 80 and over, Age Factors, Aged, Aged, 80 and over, Benzamides, Female, Humans, Imatinib Mesylate, Middle Aged, Pyrimidines, Treatment Outcome, Chronic, Adverse effect, Hematology, Leukemia, business.industry, Myeloid leukemia, Imatinib, chronic myeloid leukemia, imatinib, older age, medicine.disease, Surgery, Clinical trial, Imatinib mesylate, BCR-ABL Positive, business, medicine.drug, Myelogenous
Abstract

To assess the effect of age on response and compliance to treatment in patients with chronic myeloid leukemia (CML) we performed a sub-analysis within a phase II trial of the GIMEMA CML Working Party (CML/002/STI571). Since the WHO cut-off age to define an older patient is 65 years, among the 284 patients considered, we identified 226 (80%) younger patients (below 65 years) and 58 (20%) older patients (above 65 years) before starting imatinib. Response rates (hematologic and cytogenetic) were lower in the older age group but the probabilities of progression-free survival and overall survival (median observation time 3 years) were the same. Moreover, among complete cytogenetic responders, no differences were found in the level of molecular response between the two age groups. As might be expected, older patients experienced more adverse events, both hematologic and non-hematologic: this worsened compliance did not, however, prevent a long-term outcome similar to that of younger patients.

Published
2007

13. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia

Author

Soverini, Simona, Martinelli, Giovanni, Rosti, Gianantonio, Bassi, Simona, Amabile, Marilina, Poerio, Angela, Giannini, Barbara, Trabacchi, Elena, Castagnetti, Fausto, Testoni, Nicoletta, Luatti, Simona, De Vivo, Antonio, Cilloni, Daniela, Izzo, Barbara, Fava, Milena, Abruzzese, Elisabetta, Alberti, Daniele, Pane, Fabrizio, Saglio, Giuseppe, Baccarani, Michele, GIMEMA CML Working Party, Bocchia, Monica, Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A, Giannini B, Trabacchi E, Castagnetti F, Testoni N, Luatti S, de Vivo A, Cilloni D, Izzo B, Fava M, Abruzzese E, Alberti D, Pane F, Saglio G, Baccarani M., Soverini, S, Martinelli, G, Rosti, G, Bassi, S, Amabile, M, Poerio, A, Giannini, B, Trabacchi, E, Castagnetti, F, Testoni, N, Luatti, S, DE VIVO, A, Cilloni, D, Izzo, Barbara, Fava, M, Abruzzese, E, Alberti, D, Pane, Fabrizio, Saglio, G, and Baccarani, M.

Subjects
Myeloid, Male, Oncology, Cancer Research, DNA Mutational Analysis, Drug Resistance, TYROSINE KINASE, Piperazines, hemic and lymphatic diseases, BCR-ABL, Chromatography, High Pressure Liquid, Chromatography, Leukemia, ABL, CLINICAL RESISTANCE, Reverse Transcriptase Polymerase Chain Reaction, Statistics, CHRONIC MYELOGENOUS LEUKEMIA, Myeloid leukemia, Middle Aged, Prognosis, medicine.anatomical_structure, High Pressure Liquid, Benzamides, Cytogenetic Analysis, Leukemia, Myeloid, Chronic-Phase, Disease Progression, Imatinib Mesylate, Female, medicine.drug, Adult, medicine.medical_specialty, POSITIVE CELLS, Antineoplastic Agents, Genes, abl, Statistics, Nonparametric, Internal medicine, medicine, Humans, Point Mutation, Nonparametric, PERFORMANCE LIQUID-CHROMATOGRAPHY, ACUTE LYMPHOBLASTIC-LEUKEMIA, KINASE INHIBITOR BMS-354825, I DOSE-ESCALATION, DOMAIN MUTATIONS, Aged, Chi-Square Distribution, business.industry, Point mutation, abl, Imatinib, medicine.disease, Survival Analysis, Pyrimidines, Imatinib mesylate, Genes, Drug Resistance, Neoplasm, Immunology, Neoplasm, ABL MUTATIONS, Chronic-Phase, Bone marrow, Blast Crisis, business
Abstract

Purpose Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. Patients and Methods Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. Results Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). Conclusion Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.

Published
2005

14. Imatinib and pegylated human recombinant interferon-alpha2b in early chronic-phase chronic myeloid leukemia

Author

Baccarani, Michele, Martinelli, Giovanni, Rosti, Gianantonio, Trabacchi, Elena, Testoni, Nicoletta, Bassi, Simona, Amabile, Marilina, Soverini, Simona, Castagnetti, Fausto, Cilloni, Daniela, Izzo, Barbara, De Vivo, Antonio, Messa, Emanuela, Bonifazi, Francesca, Poerio, Angela, Luatti, Simona, Giugliano, Emilia, Alberti, Daniele, Fincato, Gianluca, Russo, Domenico, Pane, Fabrizio, Saglio, Giuseppe, GIMEMA CML Working Party, Bocchia, Monica, Baccarani, M, Martinelli, G, Rosti, G, Trabacchi, E, Testoni, N, Bassi, S, Amabile, M, Soverini, S, Castagnetti, F, Cilloni, D, Izzo, Barbara, DE VIVO, A, Messa, E, Bonifazi, F, Poerio, A, Luatti, S, Giugliano, E, Alberti, D, Fincato, G, Russo, D, Pane, Fabrizio, Saglio, G, GIMEMA WORKING PARTY ON CHRONIC MYELOID, L. E. U. K. E. M. I. A., BACCARANI M., MARTINELLI G., ROSTI G., TRABACCHI E., TESTONI N., BASSI S., AMABILE M., SOVERINI S., CASTAGNETTI F., CILLONI D., IZZO B., DE VIVO A., MESSA E., BONIFAZI F., POERIO A., LUATTI S., GIUGLIANO E., ALBERTI D., FINCATO G., RUSSO D., PANE F., SAGLIO G., and GIMEMA WORKING PARTY ON CHRONIC MYELOID LEUKEMIA

Subjects
Male, PHILADELPHIA-CHROMOSOME, Biochemistry, Gastroenterology, Piperazines, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Chronic, BCR-ABL, Leukemia, CLINICAL RESISTANCE, CHRONIC MYELOGENOUS LEUKEMIA, Myeloid leukemia, TYROSINE KINASE INHIBITOR, ABL-POSITIVE CELLS, SEQUENCE BINDING-PROTEIN, FUSION GENE TRANSCRIPTS, CYTOGENETIC RESPONSES, ANTILEUKEMIC AGENTS, Hematology, Middle Aged, Recombinant Proteins, Toxicity, Benzamides, Imatinib Mesylate, Female, Drug, medicine.drug, Adult, medicine.medical_specialty, Immunology, Alpha interferon, Interferon alpha-2, Dose-Response Relationship, chronic myeloid leukemia, Aged, Dose-Response Relationship, Drug, Humans, Interferon-alpha, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Pyrimidines, Internal medicine, medicine, Adverse effect, business.industry, Imatinib, Cell Biology, medicine.disease, Imatinib mesylate, imatinib, BCR-ABL Positive, recombinant alpha2b interferon, business, Chronic myelogenous leukemia, Myelogenous
Abstract

Since interferon-α and imatinib (IM; STI571, Glivec, Gleevec) are effective for the treatment of chronic myeloid leukemia (CML), and their mechanisms of action are different, we designed an exploratory study investigating the effects of a standard IM dose (400 mg/d) and a variable pegylated interferon-α (PegIFN) dose (50 μg/wk, 100 μg/wk, and 150 μg/wk). The criteria for dose adjustment were designed so as to ensure the delivery of the IM dose and to protect life quality. There were 76 patients with previously untreated Philadelphia (Ph)–positive CML enrolled in the study. There were 3 patients who discontinued IM and 45 patients who discontinued PegIFN. The severity of adverse events increased with increasing PegIFN dose. The IM dose could be administered to the patients who were assigned to receive 50 μg/wk or 100 μg/wk PegIFN but not to those who were assigned to receive 150 μg/wk. The median administered dose of PegIFN ranged between 32 μg/wk and 36 μg/wk. The cytogenetic response was 70% complete (Ph-neg 100%) and 83% major (Ph-neg > 65%). The BCR/ABL transcript was reduced by at least 3 logs in 68% of complete cytogenetic responders. These data of toxicity, compliance, and efficacy may assist in the design and preparation of prospective studies.

Published
2004

15. 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

16. Chronic myeloid leukemia: room for improvement?

Author

Baccarani M, Pane F, Rosti G, Russo D, and Saglio G

Subjects
Antineoplastic Combined Chemotherapy Protocols adverse effects, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Molecular Targeted Therapy, Protein Kinase Inhibitors therapeutic use
Published
2017
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