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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. 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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5. 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

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

Author

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

Subjects
Socio-culturale
Published
2015

7. 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

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

Author

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

Published
2012

9. Chromosome abnormalities additional to the Philadelphia chromosome at the diagnosis of chronic myelogenous leukemia: pathogenetic and prognostic implications

Author

Zaccaria, A, Testoni, N, Valenti, Am, Luatti, S, Tonelli, M, Marzocchi, G, Cipriani, R, Baldazzi, C, Giannini, B, Stacchini, M, Gamberini, C, Castagnetti, F, Rosti, G, Azzena, A, Cavazzini, Francesco, Cianciulli, Am, Dalsass, A, Donti, E, Giugliano, E, Gozzetti, A, Grimoldi, Mg, Ronconi, S, Santoro, A, Spedicato, F, Zanatta, L, Baccarani, M, GIMEMA Working Party on, C. M. L., Zaccaria A, Testoni N, Valenti AM, Luatti S, Tonelli M, Marzocchi G, Cipriani R, Baldazzi C, Giannini B, Stacchini M, Gamberini C, Castagnetti F, Rosti G, Azzena A, Cavazzini F, Cianciulli AM, Dalsass A, Donti E, Giugliano E, Gozzetti A, Grimoldi MG, Ronconi S, Santoro A, Spedicato F, Zanatta L, and Baccarani M

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Antineoplastic Agents, Biology, Philadelphia chromosome, Gastroenterology, Piperazines, NO, Myelogenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Internal medicine, Aged, Aged, 80 and over, Benzamides, Female, Humans, Imatinib Mesylate, Karyotyping, Middle Aged, Protein-Tyrosine Kinases, Pyrimidines, Remission Induction, Treatment Outcome, Chromosome Aberrations, Philadelphia Chromosome, Molecular Biology, Genetics, 80 and over, medicine, Chronic, Leukemia, Karyotype, Imatinib, medicine.disease, Imatinib mesylate, Immunology, BCR-ABL Positive, Sokal Score, Chronic myelogenous leukemia, medicine.drug
Abstract

Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). In some cases, on the basis of the persistence of the ACAs in Ph-negative cells after response to imatinib, a secondary origin of the Ph chromosome has been demonstrated. In this study, the possible prognostic value of this phenomenon was evaluated. Thirty-six Ph-positive CML patients were included in the study. In six patients, ACAs persisted after the disappearance of the Ph. A complete cytogenetic response (CCR) was obtained in five of these six patients, and five of six also had a high Sokal score. In all the other cases, ACAs disappeared together (in cases of response to therapy with imatinib) or persisted with the Ph (in cases of no response to imatinib). In the former cases, the primary origin of the Ph was demonstrated. CCR was obtained in 22 cases (17 with low to intermediate Sokal scores), while no response was observed in 8 patients (5 with a high Sokal score). Sokal score seems to maintain its prognostic value for patients in whom the Ph occurs as a primary event, but not in those in whom it occurs as a secondary one.

Published
2010

10. GENOME-WIDE SCREENING OF CHRONIC MYELOID LEUKEMIA PATIENTS BY SNP ARRAYS: ALTERATIONS ASSOCIATED WITH DISEASE PROGRESSION

Author

Colarossi, S., Gnani, A., Soverini, S., Castagnetti, F., Marzocchi, G., Luatti, S., Astolfi, A., Formica, S., Palandri, F., Poerio, A., Rosti, G., Testoni, N., Baccarani, M., Martinelli, G., IACOBUCCI, ILARIA, LONETTI, ANNALISA, AMABILE, MARILINA, PESSION, ANDREA, Colarossi, S., Gnani, A., Soverini, S., Castagnetti, F., Marzocchi, G., Luatti, S., Astolfi, A., Formica, S., Iacobucci, I., Lonetti, A., Palandri, F., Poerio, A., Amabile, M., Rosti, G., Pession, A., Testoni, N., Baccarani, M., and Martinelli, G.

Subjects
SNP ARRAYS, CHRONIC MYELOID LEUKEMIA (CML)
Abstract

Background. The expression of BCR-ABL gene in Chronic Myeloid Leukemia (CML) is necessary for malignant transformation but the biologic basis of the progression from Chronic Phase (CP) to Blast Crisis (BC) is poorly understood. Aim. Identifying the genomic imbalances involved in the transition into BC, before clinical features, may provide diagnostic markers of progression; so we used SNP arrays to perform a high-resolution mapping of BC CML patients genomes. Methods. We analyzed 11 patients affected by BC CML disease. Genomic DNA were extracted from bone marrow or peripheral blood mononuclear cells archived both at the time of diagnosis and progression. SNP array-based karyotyping was carried out using Affymetrix GeneChip Human Mapping arrays. Copy number (CN) analysis was performed using Hapmap normal individuals as reference set and two different softwares. Results. After exclusion of genomic copy number variations (CNVs), the following results were achieved: five patients showed huge amplifications and deletions, ranging from 30Mb to 160Mb, on chromosomes 9, 7, 3 and 6. We also found several heterozygous micro-deletions and micro-amplifications spreading all over the genome. This analysis has identified abnormalities in genes involved in apoptosis (e.g., GADD45A, FOXO3A, GAS6), DNA damage response (e.g., MYST as known as Hmof, XRCC2), tumor suppression (e.g., C/EBPdelta, LATS1), chromatin regulation (e.g., HDAC9), and genes belonged to ABC transporters (e.g., ABCB1), ras family and transcriptional/translational factors (e.g., ETV1). Moreover were found copy number changes (gain/loss) in genes associated with malignancy, in particular TNFRSF17, MET, IGFBPL1, EVI1, PTENP1. Other alterations affected key pathways including cell cycle regulation and WNT signaling. Conclusions. The use of the genomic tool Genome-Wide Human SNP array allowed us to identify, at submicroscopic level, genetic lesions in patients affected by CML in BC. Our results will be further validated by real-time PCR for the altered genes involved key pathways, while sequencing and mutation analysis will be performed on the remaining allele of putative tumor suppressor genes to identify their residual activity. All these validations and the increased number of analyzed patients will provide new insights into the genetic profiling that lead disease progression from CP to BC and consequently new opportunities to develop specific target therapies.

Published
2009

11. 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

12. Rare High Risk IgH Translocations in Newly Diagnosed Multiple Myeloma (MM): Cytogenetic Characterization and Relevance on Prognosis

Author

Marzocchi, G., primary, Testoni, N., additional, Ameli, G., additional, Pezzi, A., additional, Zamagni, E., additional, Cavallo, F., additional, Petrucci, M.T., additional, Waage, A., additional, Di Raimondo, F., additional, Patriarca, F., additional, Pantani, L., additional, Luatti, S., additional, Rambaldi, A., additional, Gamberi, B., additional, Crippa, C., additional, Zweegman, S., additional, Montefusco, V., additional, Baldazzi, C., additional, Vincelli, I., additional, Offidani, M., additional, Palumbo, A., additional, Sonneveld, P., additional, and Cavo, M., additional

Published
2015
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13. 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

15. CHROMOSOME ABNORMALITIES ADDITIONAL TO THE PHILADELPHIA CHROMOSOME AT THE DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA. PATHOGENETIC AND PROGNOSTIC IMPLICATIONS

Author

Zaccaria, A., Testoni, N., Valenti, A. M., Luatti, S., Tonelli, M., Marzocchi, G., Cipriani, R., Baldazzi, C., Giannini, B., Stacchini, M., Gamberini, C., Castagnetti, F., Rosti, G., Azzena, A., Bernardi, F., Cavazzini, Francesco, Cianciulli, A., Dalsass, A., Donti, E., Giugliano, E., Gozzetti, A., Grimoldi, M. G., Manna, M., Modaferri, B., Piovani, G., Ronconi, S., Santoro, A., Santulli, B., Spedicato, F., Zanatta, L., and on behalf of the GIMEMA WP on CML, Baccarani M.

Published
2009

22. Influence of additional chromosome abnormalities to PH on response to imatinib mesylate therapy in early chronic phase in chronic myeloid leukemia

Author

Luatti, S, 1 Marzocchi G, 1 Castagnetti F, 1 Gamberini C, 1 Baldazzi C, 1 Stacchini M, 1 Poerio A, 1 Zaccaria A, 2 Zanatta L, 3 Giugliano E, 4 Santulli B, 5 Grimoldi MG, 6 Gozzetti A, 7 Dalsass A, Piovani, Giovanna, 9 Manna M, 10 Modaferri, B, 11 Bernardi, F, 12 Bernasconi, P, 13 Kerim, S, 14 Abruzzese, E, 15 Palka, G, 16 Palandri, F, 1 Martinelli G, 1 Rosti G, 1 § Baccarani M, and 1 Testoni N1

Published
2008

23. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up (on behalf of the GIMEMA Working Party on Chronic Myeloid Leukemia)

Author

Palandri, F, Castagnetti, F, Testoni, N, Luatti, S, Marzocchi, G, Bassi, S, Breccia, M, Alimena, G, Pungolino, E, REGE CAMBRIN, G, Varaldo, R, Miglino, M, Specchia, G, Zuffa, E, Ferrara, F, Bocchia, Monica, Saglio, G, Pane, F, Alberti, D, Martinelli, G, Baccarani, M, and Rosti, G.

Published
2008

24. VARIANT PHILADELPHIA TRANSLOCATION IN EARLY CHRONIC PHASE OF CHRONIC MYELOID LEUKEMIA: RESULTS OF IMATINIB MESYLATE THERAPY (A GIMEMA WP ON CML ANALYSIS)

Author

Marzocchi, G, Luatti, S, Castagnetti, F, Gamberini, C, Baldazzi, C, Stacchini, M, Amabile, M, Iacobucci, I, Specchia, G, Sessarego, M, Giussani, U, Zanatta, L, Discepoli, G, Montaldi, A, Santoro, A, Sebastio, L, Biondi, A, Bonaldi, L, Cianciulli, A, Cuneo, Antonio, Mancini, M, Mecucci, C, Palandri, F, Rosti, G, Baccarani, M, Testoni, N, and on behalf on GIMEMA WP on CML

Published
2008

37. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up

Author

Palandri, F., primary, Castagnetti, F., additional, Alimena, G., additional, Testoni, N., additional, Breccia, M., additional, Luatti, S., additional, Rege-Cambrin, G., additional, Stagno, F., additional, Specchia, G., additional, Martino, B., additional, Levato, L., additional, Merante, S., additional, Liberati, A. M., additional, Pane, F., additional, Saglio, G., additional, Alberti, D., additional, Martinelli, G., additional, Baccarani, M., additional, and Rosti, G., additional

Published
2009
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38. Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain

Author

Soverini, S., primary, Colarossi, S., additional, Gnani, A., additional, Castagnetti, F., additional, Rosti, G., additional, Bosi, C., additional, Paolini, S., additional, Rondoni, M., additional, Piccaluga, P. P., additional, Palandri, F., additional, Giannoulia, P., additional, Marzocchi, G., additional, Luatti, S., additional, Testoni, N., additional, Iacobucci, I., additional, Cilloni, D., additional, Saglio, G., additional, Baccarani, M., additional, and Martinelli, G., additional

Published
2007
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39. A Prospective Study in Ph+ Chronic Myeloid Leukemia (CML) Patients Showing That Interphase Fluorescence in Situ Hybridization (FISH) Is Effective as Conventional Cytogenetics for Definition of Cytogenetic Response. Correlation with Molecular Response (by the GIMEMA CML WP).

Author

Testoni, Nicoletta, primary, Luatti, S., primary, Marzocchi, G., primary, Amabile, M., primary, Gamberini, C., primary, Buontempo, F., primary, Baldazzi, C., primary, Iacobucci, I., primary, Mancini, M., primary, Cuneo, A., primary, Specchia, G., primary, Kerim, S., primary, Rege-Cambrin, G., primary, Giugliano, E., primary, Giussani, U., primary, Abruzzese, E., primary, Grimoldi, M.G., primary, Modaferri, B., primary, Castagnetti, F., primary, Palandri, F., primary, Mecucci, C., primary, Bernasconi, P., primary, Gozzetti, A., primary, Palka, G., primary, Zanatta, L., primary, Zaccaria, A., primary, Martinelli, G., primary, Rosti, G., primary, and Baccarani, Michele, primary

Published
2006
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43. Imatinib 600 mg in the treatment of chronic myeloid leukemia in accelerated phase and in blast crisis. Results of a multicentric prospective study of the GIMEMA working party of civil in the long term

Author

FRANCESCA PALANDRI, Castagnetti, F., Testoni, N., Luatti, S., Bassi, S., Alimena, G., Miccolis, C., Falzetti, F., Merante, S., Abruzzese, E., Liberati, A. M., Varaldo, R., Schiamone, E. M., Tiribelli, M., Bocchia, M., Zuffa, E., Martino, B., Avanzino, P., Saglio, G., Martinelli, G., Baccarani, M., and Rosti, Gianantonio

45. CLINICAL SIGNIFICANCE OF EARLY MOLECULAR RESPONSE IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED FRONTLINE WITH IMATINIB MESYLATE

Author

Castagnetti, F., Gugliotta, G., Breccia, M., Albano, F., Abruzzese, E., Levato, L., Cavazzini, F., Lurlo, A., Stagno, F., Ferrero, D., Porretto, F., Martino, B., Rupoli, S., Intermesoli, T., Fava, C., Pierri, I., FRANCESCA PALANDRI, Venturi, C., Soverini, S., Luatti, S., Alimena, G., Pane, F., Martinelli, G., Saglio, G., Cavo, M., Baccarani, M., and Rosti, G.

48. 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

49. t(5;12)(q31;p13)/ETV6::ACSL6 and t(6;9)(p23;q34)/DEK::NUP214 concurrence in acute myeloid leukemia: an unusual association of two rare abnormalities

Author

Carmen Baldazzi, Simona Luatti, Giulia Marzocchi, Alessandra Grassi, Michele Cavo, Nicoletta Testoni, Baldazzi C., Luatti S., Marzocchi G., Grassi A., Cavo M., and Testoni N.

Subjects
Chromosome Aberrations, Oncogene Proteins, Cancer Research, Myeloproliferative Disorders, Clonal evolution, Chromosomal Proteins, Non-Histone, DEK::NUP214, ETV6::ACSL6, Translocation, Genetic, Fluorescence In situ Hydridization, Nuclear Pore Complex Proteins, Leukemia, Myeloid, Acute, AML, Recurrence, hemic and lymphatic diseases, Eosinophilia, Genetics, Humans, Cytogenetic, Poly-ADP-Ribose Binding Proteins, Molecular Biology, In Situ Hybridization, Fluorescence
Abstract

The translocation t(5;12)(q31;p13)/ETV6::ACSL6 is a rare cytogenetic abnormality, although it is reported in various myeloid malignancies. To date, only 16 cases of t(5;12) and ETV6::ACSL6 rearrangement, confirmed by either molecular or Fluorescence In Situ Hyridization (FISH) analysis, have been reported. Eosinophilia is a distinctive and common feature associated with this rearrangement. Although few cases have been described, the prognosis of patients with ETV6::ACSL6 is considered poor. We report two additional cases of t(5;12)(q31;p13)/ETV6::ACLS6 rearrangement and eosinophilia. Unusually, in our cases, the ETV6::ACSL6 rearrangement occurred at the relapse of Acute Myeloid Leukemia (AML) patients who had t(6;9)(p23;q34)/DEK::NUP214 rearrangement at disease onset. The concurrence of these two rare abnormalities has never been reported and may suggest a cooperative role of t(5;12) and t(6;9), leading to disease relapse. Moreover, at relapse, both cases presented with eosinophilia, further strengthening the association of t(5;12) with eosinophilia in myeloid malignancies. Given the poor prognosis and the non-responsiveness to tyrosine kinase inhibitors of cases of ETV6::ACSL6 rearrangement, in contrast to cases of ETV6::PDGFRB rearrangement, we recommend the introduction of testing for this abnormality in myeloid malignancies with eosinophilia.

Published
2022

50. 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

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