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

Author

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

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

Author

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

Published
2022
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3. P712: ASCIMINIB ITALIAN MANAGED ACCESS PROGRAM: EFFICACY PROFILE IN HEAVILY PRE-TREATED CML PATIENTS

Author

Breccia, M., primary, Russo Rossi, A. V., additional, Martino, B., additional, Abruzzese, E., additional, Annunziata, M., additional, Binotto, G., additional, Ermacora, A., additional, Fava, C., additional, Giaccone, L., additional, Giai, V., additional, Nardozza, A. P., additional, Coco, P., additional, Gozzini, A., additional, Levato, L., additional, Lucchesi, A., additional, Luciano, L., additional, Maria Cristina, M., additional, Rege-Cambrin, G., additional, Santoro, M., additional, Scappini, B., additional, Scortechini, A. R., additional, Sportoletti, P., additional, Trabacchi, E., additional, and Castagnetti, F., additional

Published
2022
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4. Predicting the probability of Gaucher disease in subjects with splenomegaly and thrombocytopenia

Author

Motta I, Consonni D, Stroppiano M, Benedetto C, Cassinerio E, Tappino B, Ranalli P, Borin L, Facchini L, Patriarca A, Barcellini W, Lanza F, Filocamo M, Cappellini MD, Farina F, Codeluppi K, Rivolti E, Simonetti F, Lunghi F, Perrone T, Sgherza N, Carrai V, Cafro AM, Cairoli R, Amendola A, Trabacchi E, Vallisa D, Burgo I, Federici AB, Carbone C, D’Adda M, Mannina D, Di Giacomo V, Lupparelli G, Lombardo A., Motta, I, Consonni, D, Stroppiano, M, Benedetto, C, Cassinerio, E, Tappino, B, Ranalli, P, Borin, L, Facchini, L, Patriarca, A, Barcellini, W, Lanza, F, Filocamo, M, Cappellini, M, Farina, F, Codeluppi, K, Rivolti, E, Simonetti, F, Lunghi, F, Perrone, T, Sgherza, N, Carrai, V, Cafro, A, Cairoli, R, Amendola, A, Trabacchi, E, Vallisa, D, Burgo, I, Federici, A, Carbone, C, D’Adda, M, Mannina, D, Di Giacomo, V, Lupparelli, G, and Lombardo, A

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Science, Population, Diseases, Disease, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hematologist, education, education.field_of_study, Gaucher Disease, Multidisciplinary, biology, Transferrin saturation, business.industry, beta-Glucosidase, Middle Aged, Thrombocytopenia, Dried blood spot, Algorithm, Ferritin, Multicenter study, 030220 oncology & carcinogenesis, Splenomegaly, biology.protein, Medicine, Female, business, Haematological diseases, Algorithms, Human, 030215 immunology
Abstract

Hematologists are frequently involved in the diagnostic pathway of Gaucher disease type 1 (GD1) patients since they present several hematological signs. However, GD1 is mainly underdiagnosed because of a lack of awareness. In this multicenter study, we combine the use of a diagnostic algorithm with a simple test (β-glucosidase activity on Dried Blood Spot) in order to facilitate the diagnosis in a population presenting to the hematologist with splenomegaly and/or thrombocytopenia associated with other hematological signs. In this high-risk population, the prevalence of GD1 is 3.3%. We propose an equation that predicts the probability of having GD1 according to three parameters that are routinely evaluated: platelet count, ferritin, and transferrin saturation.

Published
2021

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

Author

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

Published
2015
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10. S123 SETD2 LOSS OF FUNCTION IS A RECURRENT EVENT IN ADVANCED-PHASE CHRONIC MYELOID LEUKEMIA INDUCED BY POST-TRANSLATIONAL MECHANISMS THAT CAN BE THERAPEUTICALLY TARGETED

Author

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

Published
2019
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12. A population-based study of chronic myeloid leukemia patients treated with imatinib in first line

Author

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

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

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

Published
2016

13. The long term outcome of the patients with chronic myeloid leukemia (CML) who have achieved complete cytogenetic response (CCgR) to interferon-alpha (IFN alpha). A collaborative European study of 317 cases

Author

Bonifazi, F, De Vivo, A, Rosti, G, Guilhot, F, Guilhot, J, Trabacchi, E, Hehlmann, R, Hochhaus, A, Shepherd, P, Steegmann, J, Kluin-Nelemans, H, Thaler, J, Simonsson, B, Louwagie, A, Reiffers, J, Mahon, F, Montefusco, E, Alimena, G, Hasford, J, Richards, S, Saglio, G, Testoni, N, Martinelli, G, Tura, S, and Baccarani, M

Published
2016

14. Long term outcome of ph+ cml patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era

Author

Malagola M, Breccia M, Skert C, Cancelli V, Cattina F, Liberati AM, Tiribelli M, Annunziata M, Trabacchi E, De Vivo A, Fogli M, Stagno F, Pica G, Iurlo A, Pregno P, Abruzzese E, Pardini S, Bocchia M, Russo S, Pierri I, Lunghi M, Barulli S, Merante S, Mandelli F, Alimena G, Russo D., SOVERINI, SIMONA, IACOBUCCI, ILARIA, CASTAGNETTI, FAUSTO, MARTINELLI, GIOVANNI, ROSTI, GIANANTONIO, BACCARANI, MICHELE, Malagola M, Breccia M, Skert C, Cancelli V, Soverini S, Iacobucci I, Cattina F, Liberati AM, Tiribelli M, Annunziata M, Trabacchi E, De Vivo A, Castagnetti F, Martinelli G, Fogli M, Stagno F, Pica G, Iurlo A, Pregno P, Abruzzese E, Pardini S, Bocchia M, Russo S, Pierri I, Lunghi M, Barulli S, Merante S, Mandelli F, Alimena G, Rosti G, Baccarani M, and Russo D.

Subjects
Adult, Male, EUROPE, Fusion Proteins, bcr-abl, MULTICENTER, Antineoplastic Agents, Piperazines, RECOMMENDATIONS, Young Adult, CHRONIC MYELOID-LEUKEMIA, CHRONIC MYELOGENOUS LEUKEMIA, MOLECULAR RESPONSE, RESIDUAL DISEASE, T-LYMPHOCYTES, ALPHA, TRANSCRIPTS, INTERFERON THERAPY, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, Humans, BCR-ABL, Protein Kinase Inhibitors, Aged, Retrospective Studies, Drug Substitution, Remission Induction, Interferon-alpha, Middle Aged, Cross-Sectional Studies, Pyrimidines, Treatment Outcome, Benzamides, Imatinib Mesylate, Female, CHRONIC MYELOID LEUKEMIA (CML), Follow-Up Studies
Abstract

Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty-seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow-up, the BCR-ABL transcripts level was available in 96/101 living patients (95%) The BCR-ABL:ABL ratio was between 0.1 and 0.01% (MR(3.0) ) in 17%, and less than 0.01% (MR(4.0) ) in 81% of patients. No patient was completely molecular negative (MR(4.5) or MR(5.0) ). The OS at 10 and 20 years is 92 and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR(4.0) . Complete molecular response (MR(4.5) or MR(5.0) ) seems to be unnecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα.

Published
2014

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

Author

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

Subjects
Socio-culturale
Published
2016

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

Author

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

Subjects
Socio-culturale
Published
2016

17. Molecular response to imatinib in late chronic-phase chronic myeloid leukemia

Author

ROSTI G, MARTINELLI G, BASSI S, AMABILE M, TRABACCHI E, GIANNINI B, CILLONI D, IZZO, BARBARA, DE VIVO A, TESTONI N, CAMBRIN GR, BONIFAZI F, SOVERINI S, LUATTI S, GOTTARDI E, ALBERTI D, PANE, FABRIZIO, SALVATORE F, SAGLIO G, BACCARANI M, STUDY COMMITTEE, ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID LEUKEMIA, WRITING COMMITTEE, ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID L.E.U.K.E.M.I.A., ROSTI G., MARTINELLI G., BASSI S., AMABILE M., TRABACCHI E., GIANNINI B., CILLONI D., IZZO B., DE VIVO A., TESTONI N., CAMBRIN G. R., BONIFAZI F., SOVERINI S., LUATTI S., GOTTARDI E., ALBERTI D., PANE F., SALVATORE F., SAGLIO G., BACCARANI M., STUDY COMMITTEE, ITALIAN COOPERATIVE STUDY GROUP ON CHRONIC MYELOID LEUKEMIA, WRITING COMMITTEE, Rosti, G, Martinelli, G, Bassi, S, Amabile, M, Trabacchi, E, Giannini, B, Cilloni, D, Izzo, Barbara, DE VIVO, A, Testoni, N, Cambrin, Gr, Bonifazi, F, Soverini, S, Luatti, S, Gottardi, E, Alberti, D, Pane, Fabrizio, Salvatore, F, Saglio, G, Baccarani, M, Study, Committee, ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID, Leukemia, Writing, Committee, and ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID, L. E. U. K. E. M. I. A.

Subjects
POLYMERASE-CHAIN-REACTION, Immunology, IMATINIB MESYLATE, Alpha interferon, Antineoplastic Agents, Bone Marrow Cells, INTERFERON-ALPHA THERAPY, Genes, abl, PHILADELPHIA-CHROMOSOME, Biochemistry, Piperazines, Myelogenous, Recurrence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Humans, Medicine, CHRONIC MYELOGENOUS LEUKEMIA, TYROSINE KINASE INHIBITOR, MINIMAL-RESIDUAL-DISEASE, BONE-MARROW-TRANSPLANTATION, FUSION GENE TRANSCRIPTS, ABL-POSITIVE CELLS, BCR-ABL, Philadelphia-positive, MOLECULAR RESPONSE, CHRONIC MYELOID LEUKEMIA, ABL, business.industry, breakpoint cluster region, Myeloid leukemia, Imatinib, Cell Biology, Hematology, medicine.disease, Leukemia, Pyrimidines, Treatment Outcome, Imatinib mesylate, Benzamides, Cancer research, beta 2-Microglobulin, business, Follow-Up Studies, medicine.drug
Abstract

Imatinib is a tyrosine-kinase inhibitor that binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia (CML). In these patients measuring response by molecular techniques is clearly required. We determined the cytogenetic and molecular response (CgR, MR) to imatinib in 191 patients with late chronic-phase Philadelphia-positive (Ph+) CML, previously treated with interferon α. MR was assessed with real-time quantitative (TaqMan) reverse transcription–polymerase chain reaction and was expressed as the ratio between BCR/ABL and β2-microglobulin × 100, the lowest level of detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in 85 (44%) of 191 patients and was maintained for 2 years in 67 (79%) of 85 patients. A reduction of the transcript level of more than 2 logs was achieved in all but 9 patients with CCgR versus none of 23 with partial CgR. In the CCgRs the median value of the MR was 0.0008 after 12 months and 0.0001 after 24 months, with the transcript level undetectable in 22 cases. We conclude that in CCgRs the degree of MR may vary from 2 to more than 4 logs, and that there is a progressive decrease of transcript level by time. Only 1 of 22 negative cases has had a relapse as yet.

Published
2004

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

Author

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

Subjects
Socio-culturale
Published
2015

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

Author

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, Alimena, G, GAMBACORTI PASSERINI, CARLO, Alimena, G., 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, Alimena, G, GAMBACORTI PASSERINI, CARLO, and Alimena, G.

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

20. Deep Molecular Response to Nilotinib As First-Line Treatment of BCR-ABL plus CML in Early Chronic Phase: A Phase 3b Multicenter Study of the Gimema CML Working Party

Author

Castagnetti, F, Gugliotta, G, Breccia, M, Martino, B, Rossi, G, Stagno, F, Turri, D, Tiribelli, M, Trabacchi, E, Isidori, A, Pierri, I, Leonardi, G, Pregno, P, Carella, Am, Bochicchio, Mt, Testoni, N, Soverini, S, Specchia, G, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Baccarani, M, and Rosti, G

Published
2014

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

Author

Castagnetti, F, Gugliotta, G, Baccarani, M, Breccia, M, Specchia, G, Levato, L, Abruzzese, E, Rossi, G, Iurlo, A, Martino, B, Pregno, P, Stagno, F, Cuneo, A, Bonifacio, M, Gobbi, M, Russo, D, Gozzini, A, Tiribelli, M, De Vivo, A, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Salvi, F, Pini, M, Leoni, P, Rupoli, S, Galieni, P, Bigazzi, C, Cantore, N, Palmieri, F, Albano, F, Russo Rossi, A, Rambaldi, A, Intermesoli, T, Palandri, F, Testoni, N, Luatti, S, Soverini, S, Iacobucci, I, Bochicchio, 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, D'Emilio, A, GAMBACORTI PASSERINI, CARLO, 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, D'Emilio, A, GAMBACORTI PASSERINI, CARLO, and D'Emilio, A.

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 CMLWP 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.

Published
2015

22. FOLLOW UP A LUNGO TERMINE DEI PAZIENTI CON LMC-PH+ IN RISPOSTA CITOGENETICA COMPLETA CON TERAPIA INCLUDENTE INTERFERONE NELL’ERA IMATINIB - PROTOCOLLO GIMEMA CML0509

Author

Russo, D, Alimena, G, Colombi, C, Breccia, M, Soverini, S, Iacobucci, I, Cattina, F, Martinelli, G, Testoni, N, Liberati, Am, Appolloni, V, Tiribelli, M, Fanin, R, Ferrara, F, Annunziata, M, Trabacchi, E, Vallisa, D, De Vivo, A, Castagnetti, F, Fogli, M, Durante, S, Di Raimondo, F, Stagno, F, Carella, Am, Pica, G, Cortelezzi, A, Iurlo, A, Pregno, P, Vitolo, U, Abruzzese, E, De Fabritiis, P, Longinotti, M, Pardini, S, Musolino, C, Russo, S, Gobbi, M, Pierri, I, Gaidano, G, Lunghi, M, Visani, G, Barulli, S, Cazzola, M, Merante, S, Skert, C, Malagola, M, Rosti, G, Mandelli, F, and Baccarani, M

Published
2012

23. Results of high dose of imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase trial of the GIMEMA Working Party

Author

Castagnetti, F, Palandri, F, Amabile, M, Testoni, N, Luatti, S, Soverini, S, Iacobucci, I, Breccia, M, Rege Cambrin, G, Stagno, F, Specchia, G, Galieni, P, Iuliano, F, Pane, F, Saglio, G, Alimena, G, Martinelli, G, Baccarani, M, Rostilevis, A, Pini, M, Bigazzi, C, Liso, V, Bassan, R, Intermesoli, T, Marzocchi, G, Capucci, A, Rossi, G, Girasoli, M, Giustolisi, R, Levato, L, Peta, A, Musolino, Caterina, Luciano, L, Rotoli, B, Cilloni, D, Fava, C, Semenzato, G, Musso, M, Porretto, F, Barulli, S, Visani, G, Di Lorenzo, R, Fioritoni, G, Trabacchi, E, Vallisa, D, Leone, G, Sica, S, Abruzzese, E, Foà, R, Petti, Mc, Bocchia, M, Lauria, F, Gherlinzoni, F, Gallo, E, and Pregno, P.

Published
2009

29. Other targets for Imatinib therapy

Author

Martinelli, G, Piccaluga, Pp, Malagola, Michele, Soverini, S, Rondoni, M, Isidori, A, Giannini, B, Grafone, T, Ottavini, E, De Vivo, A, Bonifazi, F, Bosi, C, Bianchini, M, Terragna, C, Fiacchini, M, Ricci, P, Visani, G, Russo, Domenico, Bassi, S, Trabacchi, E, Rosti, G, Buonamici, S, Alberti, D, and Baccarani, M.

Published
2003

34. The long term outcome of the patients with chronic myeloid leukemia (CML) who have achieved complete cytogenetic response (CCgR) to interferon-alpha (IFN alpha). A collaborative European study of 317 cases

Author

Bonifazi, F, De Vivo, A, Rosti, G, Guilhot, F, Guilhot, J, Trabacchi, E, Hehlmann, R, Hochhaus, A, Shepherd, P, Steegmann, JL, Kluin-Nelemans, HC, Thaler, J, Simonsson, B, Louwagie, A, Reiffers, J, Mahon, FX, Montefusco, E, Alimena, G, Hasford, J, Richards, S, Saglio, G, Testoni, N, Martinelli, G, Tura, S, Baccarani, M, and CML, ESGI

Published
2001

35. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders

Author

Bonifazi, F, de Vivo, A, Rosti, G, Guilhot, F, Guilhot, J, Trabacchi, E, Hehlmann, R, Hochhaus, A, Shepherd, P. C, Steegmann, J. L, Kluin Nelemans, H. C, Thaler, J, Simonsson, B, Louwagie, A, Reiffers, J, Mahon, F. X, Montefusco, E, Alimena, G, Hasford, J, Richards, S, Saglio, Giuseppe, Testoni, N, Martinelli, G, Tura, S, Baccarani, M, European Study Group on Interferon in Chronic Myeloid Leukemia, Italian Cooperative Study Group on CML, France Intergroup of CML, German CML Study Group, UK Medical Research Council Working Party on CML, Spanish CML Study Group, Australian CML Study Group, and Swedish CML Study Group

Subjects
Male, HYDROXYUREA, bcr-abl, Fusion Proteins, bcr-abl, Biochemistry, THERAPY, Hydroxycarbamide, Risk Factors, Cause of Death, Medicine, Life Tables, Chronic, media_common, Bone Marrow Transplantation, Tumor, Leukemia, Remission Induction, CHRONIC MYELOGENOUS LEUKEMIA, Myeloid leukemia, Hematology, BONE-MARROW TRANSPLANTATION, Middle Aged, Combined Modality Therapy, Recombinant Proteins, Europe, Treatment Outcome, SURVIVAL, Female, medicine.drug, Adult, medicine.medical_specialty, POLYMERASE-CHAIN-REACTION, CLINICAL DECISION-MAKING, Immunology, Alpha interferon, MINIMAL RESIDUAL DISEASE, Antineoplastic Agents, Interferon alpha-2, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Biomarkers, Tumor, media_common.cataloged_instance, Humans, Immunologic Factors, European union, Survival rate, Survival analysis, Aged, Retrospective Studies, business.industry, CHRONIC-PHASE, Fusion Proteins, Interferon-alpha, Cell Biology, REMISSION, medicine.disease, Minimal residual disease, Survival Analysis, Follow-Up Studies, Surgery, BCR-ABL Positive, business, Biomarkers, Chronic myelogenous leukemia, Myelogenous
Abstract

Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-α (IFN-α), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-α alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-α treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients.

Published
2001

36. A rapid reduction of Bcr/Abl transcripts is associated with an early cytogenetic response to Glivec (STI571) in chronic myeloid leukemia in chronic phase: a study of the Italian cooperative study group on CML

Author

Martinelli, G, Pane, F, Saglio, G, Alberti, D, Amabile, M, Ottaviani, E, Intrieri, Mariano, Salvatore, F, Tiribelli, M, Rosti, G, De Vivo, A, Bonifazi, F, Trabacchi, E, Bassi, S, Russo, D, Testoni, N, Ruggeri, D, Zardini, C, Giannini, B, Buonamici, S, Baccarani, M, and Tura, S.

Published
2001

37. Hematologic, cytogenetic and molecular response to Glivec (STI571) in chronic phase Ph+ chronic myeloid leukemia patients who failed IFNa or did not tolerate IFNa: a prospective study of the Italian cooperative study group on CML

Author

Rosti, G, Alberti, D, De Vivo, A, Bonifazi, F, Trabacchi, E, Bassi, S, Vecchi, K, Testoni, N, Ruggeri, D, Amabile, M, Tiribelli, M, Marin, L, Rege Cambrin, G, Scaravaglio, P, Pane, F, Intrieri, Mariano, Salvatore, F, Martinelli, G, Zardini, C, Giannini, B, Saglio, G, Montefusco, E, Tura, S, and Baccarani, M.

Published
2001

39. Hematologic, cytogenetic and molecular response to Glivec (STI571) in Ph+ chronic myeloid leukemia (CML) in accelerated and blastic phase: a prospective study of the Italian cooperative study group on CML

Author

Rosti, G, Alberti, D, De Vivo, A, Bonifazi, F, Trabacchi, E, Bassi, S, Vecchi, K, Testoni, N, Amabile, M, Ottaviani, E, Tiribelli, M, Gottardi, E, Cilloni, D, Pane, F, Intrieri, Mariano, Salvatore, F, Martinelli, G, Saglio, G, Montefusco, E, Tura, S, and Baccarani, M.

Published
2001

43. Chronic myeloid leukemia and interferon-alpha: a study of completecytogenetic responders.

Author

Bonifazi, F, de Vivo, A, Rosti, G, Guilhot, F, Guilhot, J, Trabacchi, E, Hehlmann, R, Hochhaus, A, Shepherd, PC, Steegmann, JL, Kluin-Nelemans, HC, Thaler, J, Simonsson, B, Louwagie, A, Reiffers, J, Mahon, FX, Montefusco, E, Alimena, G, Hasford, J, Richards, S, Saglio, G, Testoni, N, Martinelli, G, Tura, S, Baccarani, M, Bonifazi, F, de Vivo, A, Rosti, G, Guilhot, F, Guilhot, J, Trabacchi, E, Hehlmann, R, Hochhaus, A, Shepherd, PC, Steegmann, JL, Kluin-Nelemans, HC, Thaler, J, Simonsson, B, Louwagie, A, Reiffers, J, Mahon, FX, Montefusco, E, Alimena, G, Hasford, J, Richards, S, Saglio, G, Testoni, N, Martinelli, G, Tura, S, and Baccarani, M

Published
2001

44. Development of hypogammaglobulinemia in patients treated with imatinib for chronic myeloid leukemia or gastrointestinal stromal tumor

Author

Santachiara, R., primary, Maffei, R., additional, Martinelli, S., additional, Arcari, A., additional, Piacentini, F., additional, Trabacchi, E., additional, Alfieri, P., additional, Ferrari, A., additional, Leonardi, G., additional, Luppi, G., additional, Longo, G., additional, Vallisa, D., additional, Marasca, R., additional, and Torelli, G., additional

Published
2008
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47. A phase II study of alpha-interferon and oral arabinosyl cytosine (YNK01) in chronic myeloid leukemia.

Author

Rosti, G, Bonifazi, F, Trabacchi, E, De Vivo, A, Bassi, S, Martinelli, G, Testoni, N, Russo, D, and Baccarani, M

Subjects
ANTINEOPLASTIC agents, CLINICAL trials, COMPARATIVE studies, RESEARCH methodology, MEDICAL cooperation, ORAL drug administration, PATIENT compliance, PRODRUGS, PROTEINS, RECOMBINANT proteins, RESEARCH, EVALUATION research, CHRONIC myeloid leukemia, TREATMENT effectiveness, DISEASE remission, CYTARABINE, DISEASE complications
Abstract

YNK01 (Starasid) is a prodrug that is adsorbed in the gut and is transformed in the liver in arabinosyl cytosine (AC). Low-dose AC (LDAC) is useful for the treatment of Philadelphia positive (Ph+) chronic myeloid leukemia (CML), especially in combination with alpha-interferon (alphaIFN). The use of YNK01 can avoid the daily s.c. injection of conventional AC. To assess the safety and the efficacy of alphaIFN and YNK01, we enrolled 86 consecutive previously untreated chronic phase Ph+ CML patients in a phase II study of alphaIFN (Intron-A) 5 MIU/m(2) daily and YNK01 600 mg daily 14 days a month. The 6-month complete hematologic response and the 12-month major cytogenetic response rates were 78 and 28%, respectively. In a prior study of alphaIFN and conventional LDAC, they were 62 and 22%, respectively. However, the compliance to the treatment was poor, with 25% of cases discontinuing the treatment within the first year. This was not because of the severity of the side effects but because of the frequency, duration and repetition of the side effects, for an overall frequency of 13.17 adverse events, mostly grade 1 and 2, per patient per year. Therefore, the study of this effective combination is being pursued, testing lower doses of alphaIFN and YNK01. [ABSTRACT FROM AUTHOR]

Published
2003
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48. Ibrutinib as a bridge to transplant in high-risk chronic lymphocytic leukemia: A case report and review of the literature

Author

Arcari Annalisa, Bassi Simona, Pochintesta Lara, Trabacchi Elena, Moroni Carlo Filippo, Rossi Angela, Zanlari Luca, and Vallisa Daniele

Subjects
Chronic lymphocytic leukemia, B-cell receptor inhibitors, Allogeneic hematopoietic stem cell transplantation, TP53 mutation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The treatment landscape of chronic lymphocytic leukemia (CLL) has been challenged by the advent of novel classes of drugs, such as B-cell receptor (BCR)-inhibitors and BCL-2 antagonists. In selected high-risk patients, the choice to start allogeneic hematopoietic stem cell transplantation (alloHCT) or continue these agents is a matter of debate. Furthermore, published data about the impact on the feasibility of alloHCT and the optimal timing of administration are limited. Here we present a case of relapsed TP53 mutated CLL treated with ibrutinib as a bridge to alloHCT, discussing risks and benefits of different treatment options in a “real life” situation.

Published
2017
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50. Real-time quantification of different types of bcr-abl transcript in chronic myeloid leukemia

Author

Amabile, M., Giannini, B., Testoni, N., Montefusco, V., Rosti, G., Zardini, C., CAROLINA TERRAGNA, Buonamici, S., Ottaviani, E., Soverini, S., Fiacchini, M., Bassi, S., Vivo, A., Trabacchi, E., Saglio, G., Pane, F., Baccarani, M., Tura, S., Martinelii, G., Amabile, M., Giannini, B., Testoni, N., Montefusco, V., Rosti, G., Zardini, C., Terragna, C., Buonamici, S., Ottaviani, E., Soverini, S., Fiacchini, M., Bassi, S., DE VIVO, A., Trabacchi, E., Saglio, G., Pane, Fabrizio, Baccarani, M., Tura, S., and Martinelli, G.

Subjects
Male, Leukemia, Reverse Transcriptase Polymerase Chain Reaction, Messenger, abl, Genes, abl, Sensitivity and Specificity, Genes, Bone Marrow, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Methods, RNA, Humans, BCR-ABL Positive, Female, RNA, Messenger, Chronic, Myelogenous
Abstract

The most common translocation in chronic myeloid leukemia (CML) t(9;22) (q34;q22) produces the BCR/ABL fusion gene. We set up and evaluated a rapid and reliable real-time reverse-transcription-polymerase chain reaction (RT-PCR) approach using TaqMan technology for detection and quantification of bcr-abl transcripts in CML patients at diagnosis and during therapy.A pair of primers and probe complementary to ABL exon 2 were designed, enabling detection of the most frequent bcr-abl transcripts, and also of the normal ABL-Ia transcript as an internal control. Conditions were established to amplify less than 1(-10) target molecules/reaction and detect one CML cell in 10(6) cells from healthy donors. To determine the utility of the assay, we quantified the bcr-abl/ABL-Ia ratio in 59 bone marrow samples (45 samples with evidence of different Ph+ chromosome percentages and 14 samples in complete cytogenetic remission) from 48 CML patients, 34 of them at diagnosis and 14 in clinical remission (CR). In 14 cases, this ratio was compared with results obtained by a competitive-quantitative RT-PCR/capillary electrophoresis method from contemporary specimens.By real-time RT-PCR, the median value of bcr-abl/ABL-Ia ratio at diagnosis was 15.334 (range 3.3-28.81) and fell to 0.9 (range 0.003-26.1) in CR. The median value of bcr-abl/ABL-Ia ratio at cytogenetic remission was 0.7 (range 0.003-2.83). The real-time bcr-abl/ABL-Ia ratios correlated with those obtained by competitive RT-PCR (p0.0001) and the percentage of Ph+ metaphases (p0.0001). The high sensitivity and specificity of the real-time RT-PCR procedure was confirmed in all 14 patients with minimal residual disease. INTERPRETATION AND CONCLUSIONS. We conclude that this real-time RT-PCR procedure is a reliable and sensitive method of monitoring CML patients after therapy, and that the bcr-abl/ABL-Ia ratio correlates strongly with cytogenetic analysis.

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