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1. Direct determination of chronic myeloid leukemia prevalence in Lombardy—Italy: Global implications.

Author

Polverelli, N., Anghilieri, M., Elena, C., Intermesoli, T., Pungolino, E., D'Adda, M., Iurlo, A., Maffioli, M., Lunghi, F., Bertolli, V., Orofino, N., Sissa, C., Fiamenghi, C., Gardellini, A., Ubezio, M., Carraro, M. C., Corradini, P., Giglio, F., Pasquini, M. C., and Palazzolo, R.

Subjects
CHRONIC myeloid leukemia, PROTEIN-tyrosine kinase inhibitors, RECORD collecting, IMATINIB, HEMATOLOGY
Abstract

Lombardy represents the largest region of Italy by population, with almost 10 million residents, a dimension similar to a medium size country like Sweden or Belgium. The CML subcommittee of the Lombardy Hematology Network (REL‐CML) conducted a study at the beginning of 2023. Prevalence was calculated by direct input from the 21 centers participating in REL‐CML. Tyrosine Kinase Inhibitors (TKI) prescription records collected from the ARIA regional registry were used to estimate the number of CML patients followed in smaller centers not participating in REL‐CML. A total of 2285 patients were registered, representing a prevalence of 0.23 ‰. These data were compared to a similar census conducted in 2005, at the beginning of the TKI era, where a prevalence of 0.029‰ was calculated. This indicates that an almost 10 times increase took place during this period of time. Imatinib represents the most frequently prescribed first‐line TKI; its use in 2022 still represented 75% of total first line prescriptions. An increased concentration of the care of CML patients in specialized REL centers with a decreased dispersion of patients in small centers was also evident over this 18 year period of time. Nineteen % of patients discontinued treatment, highlighting persisting logistical and biological challenges; one some recommendations on CML management are included to this aim. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study

Author

Zambrotta, G, Nicolini, F, Assouline, S, Busque, L, Pungolino, E, Abruzzese, E, Miggiano, M, Elena, C, Alvarez-Larran, A, Triguero, A, Iurlo, A, Bucelli, C, Cerrano, M, Capodanno, I, Lunghi, F, le Coutre, P, Galimberti, S, Caocci, G, Maffioli, M, Stagno, F, Saussele, S, Piazza, R, Druker, B, Fava, C, Guglielmana, V, Colombo, F, Antolini, L, Gambacorti-Passerini, C, Zambrotta G. P. M., Nicolini F. E., Assouline S., Busque L., Pungolino E., Abruzzese E., Miggiano M. C., Elena C., Alvarez-Larran A., Triguero A., Iurlo A., Bucelli C., Cerrano M., Capodanno I., Lunghi F., le Coutre P., Galimberti S., Caocci G., Maffioli M., Stagno F., Saussele S., Piazza R., Druker B. J., Fava C., Guglielmana V., Colombo F., Antolini L., Gambacorti-Passerini C., Zambrotta, G, Nicolini, F, Assouline, S, Busque, L, Pungolino, E, Abruzzese, E, Miggiano, M, Elena, C, Alvarez-Larran, A, Triguero, A, Iurlo, A, Bucelli, C, Cerrano, M, Capodanno, I, Lunghi, F, le Coutre, P, Galimberti, S, Caocci, G, Maffioli, M, Stagno, F, Saussele, S, Piazza, R, Druker, B, Fava, C, Guglielmana, V, Colombo, F, Antolini, L, Gambacorti-Passerini, C, Zambrotta G. P. M., Nicolini F. E., Assouline S., Busque L., Pungolino E., Abruzzese E., Miggiano M. C., Elena C., Alvarez-Larran A., Triguero A., Iurlo A., Bucelli C., Cerrano M., Capodanno I., Lunghi F., le Coutre P., Galimberti S., Caocci G., Maffioli M., Stagno F., Saussele S., Piazza R., Druker B. J., Fava C., Guglielmana V., Colombo F., Antolini L., and Gambacorti-Passerini C.

Abstract

Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003–0.138]) in the overall group; 0.0 (95% CI [0–0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004–0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p <.0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated.

Published
2023

4. Occurrence of L1M Elements in Chromosomal Rearrangements Associated to Chronic Myeloid Leukemia (CML): Insights from Patient-Specific Breakpoints Characterization

Author

L’Abbate, A, Moretti, V, Pungolino, E, Micheloni, G, Valli, R, Frattini, A, Barcella, M, Acquati, F, A Reinbold, R, Costantino, L, Ferrara, F, Trojani, A, Ventura, M, Porta, G, Cairoli, R, Alberto L’Abbate, Vittoria Moretti, Ester Pungolino, Giovanni Micheloni, Roberto Valli, Annalisa Frattini, Matteo Barcella, Francesco Acquati, Rolland A Reinbold, Lucy Costantino, Fulvio Ferrara, Alessandra Trojani, Mario Ventura, Giovanni Porta, Roberto Cairoli, L’Abbate, A, Moretti, V, Pungolino, E, Micheloni, G, Valli, R, Frattini, A, Barcella, M, Acquati, F, A Reinbold, R, Costantino, L, Ferrara, F, Trojani, A, Ventura, M, Porta, G, Cairoli, R, Alberto L’Abbate, Vittoria Moretti, Ester Pungolino, Giovanni Micheloni, Roberto Valli, Annalisa Frattini, Matteo Barcella, Francesco Acquati, Rolland A Reinbold, Lucy Costantino, Fulvio Ferrara, Alessandra Trojani, Mario Ventura, Giovanni Porta, and Roberto Cairoli

Abstract

Chronic myeloid leukemia (CML) is a rare myeloproliferative disorder caused by the reciprocal translocation t(9;22)(q34;q11) in hematopoietic stem cells (HSCs). This chromosomal translocation results in the formation of an extra-short chromosome 22, called a Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene responsible for the expression of a constitutively active tyrosine kinase that causes uncontrolled growth and replication of leukemic cells. Mechanisms behind the formation of this chromosomal rearrangement are not well known, even if, as observed in tumors, repetitive DNA may be involved as core elements in chromosomal rearrangements. We have participated in the explorative investigations of the PhilosoPhi34 study to evaluate residual Ph+ cells in patients with negative FISH analysis on CD34+/lin- cells with gDNA qPCR. Using targeted next-generation deep sequencing strategies, we analyzed the genomic region around the t(9;22) translocations of 82 CML patients and one CML cell line and assessed the relevance of interspersed repeat elements at breakpoints (BP). We found a statistically higher presence of LINE elements, in particular belonging to the subfamily L1M, in BP cluster regions of both chromosome 22 and 9 compared to the whole human genome. These data suggest that L1M elements could be potential drivers of t(9;22) translocation leading to the generation of the BCR-ABL1 chimeric gene and the expression of the active BCR-ABL1-controlled tyrosine kinase chimeric protein responsible for CML.

Published
2023

5. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists

Author

De Stefano, V, Ruggeri, M, Cervantes, F, Alvarez-Larrán, A, Iurlo, A, Randi, M L, Elli, E, Finazzi, M C, Finazzi, G, Zetterberg, E, Vianelli, N, Gaidano, G, Rossi, E, Betti, S, Nichele, I, Cattaneo, D, Palova, M, Ellis, M H, Cacciola, R, Tieghi, A, Hernandez-Boluda, J C, Pungolino, E, Specchia, G, Rapezzi, D, Forcina, A, Musolino, C, Carobbio, A, Griesshammer, M, Sant’Antonio, E, Vannucchi, A M, and Barbui, T

Published
2016
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6. Nilotinib-induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study

Author

Pungolino, E, D'Adda, M, De Canal, G, Trojani, A, Perego, A, Elena, C, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Artale, S, Anghilieri, M, Molteni, A, Caramella, M, Baruzzo, G, Nichelatti, M, Di Camillo, B, Cairoli, R, Pungolino E, D'adda M, De Canal G, Trojani A, Perego A, Elena C, Lunghi F, Turrini M, Borin L, Iurlo A, Latargia ML, Carraro MC, Spina F, Artale S, Anghilieri M, Molteni A, Caramella M, Baruzzo G, Nichelatti M, Di Camillo B, Cairoli R, Pungolino, E, D'Adda, M, De Canal, G, Trojani, A, Perego, A, Elena, C, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Artale, S, Anghilieri, M, Molteni, A, Caramella, M, Baruzzo, G, Nichelatti, M, Di Camillo, B, Cairoli, R, Pungolino E, D'adda M, De Canal G, Trojani A, Perego A, Elena C, Lunghi F, Turrini M, Borin L, Iurlo A, Latargia ML, Carraro MC, Spina F, Artale S, Anghilieri M, Molteni A, Caramella M, Baruzzo G, Nichelatti M, Di Camillo B, and Cairoli R

Abstract

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

Published
2021

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

Author

Diral, E, Mori, S, Antolini, L, Abruzzese, E, Le Coutre, P, Martino, B, Pungolino, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Gozzini, A, Andrade-Campos, M, Stagno, F, Iurlo, A, Pirola, A, Fontana, D, Petiti, J, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti Passerini, C, Diral E., Mori S., Antolini L., Abruzzese E., Le Coutre P., Martino B., Pungolino E., Elena C., Bergamaschi M., Assouline S., Di Bona E., Gozzini A., Andrade-Campos M., Stagno F., Iurlo A., Pirola A., Fontana D., Petiti J., Bonanomi M. L., Crivori P., Piazza R., Fava C., Gambacorti Passerini C., Diral, E, Mori, S, Antolini, L, Abruzzese, E, Le Coutre, P, Martino, B, Pungolino, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Gozzini, A, Andrade-Campos, M, Stagno, F, Iurlo, A, Pirola, A, Fontana, D, Petiti, J, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti Passerini, C, Diral E., Mori S., Antolini L., Abruzzese E., Le Coutre P., Martino B., Pungolino E., Elena C., Bergamaschi M., Assouline S., Di Bona E., Gozzini A., Andrade-Campos M., Stagno F., Iurlo A., Pirola A., Fontana D., Petiti J., Bonanomi M. L., Crivori P., Piazza R., Fava C., and Gambacorti Passerini C.

Abstract

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

Published
2020

8. Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study

Author

Hochhaus, A, Gambacorti Passerini, C, Abboud, C, Gjertsen, B, Brummendorf, T, Smith, B, Ernst, T, Giraldo-Castellano, P, Olsson-Stromberg, U, Saussele, S, Bardy-Bouxin, N, Viqueira, A, Leip, E, Russell-Smith, T, Leone, J, Rosti, G, Watts, J, Giles, F, Abruzzese, E, Akard, L, Bosi, A, Cervantes, F, Charbonnier, A, Di Raimondo, F, Etienne, G, Garcia Gutierrez, V, Guerci-Bresler, A, Hjorth-Hansen, H, Karsenti, J, Kelly, K, Le Coutre, P, Martinez Chamorro, C, Oehler, V, Orti Pascual, G, Petzer, A, Pungolino, E, Rege-Cambrin, G, Rigal-Huguet, F, Roboz, G, Rousselot, P, Sanchez-Guijo, F, Sanz Santillana, G, Schafhausen, P, Scheid, C, Schmidt, S, Specchia, G, Steegmann, J, Stenke, L, Hochhaus A., Gambacorti Passerini C., Abboud C., Gjertsen B. T., Brummendorf T. H., Smith B. D., Ernst T., Giraldo-Castellano P., Olsson-Stromberg U., Saussele S., Bardy-Bouxin N., Viqueira A., Leip E., Russell-Smith T. A., Leone J., Rosti G., Watts J., Giles F. J., Abruzzese E., Akard L. P., Bosi A., Cervantes F., Charbonnier A., Di Raimondo F., Etienne G., Garcia Gutierrez V., Guerci-Bresler A. P., Hjorth-Hansen H., Karsenti J. M., Kelly K. R., Le Coutre P., Martinez Chamorro C., Oehler V. G., Orti Pascual G., Petzer A., Pungolino E., Rege-Cambrin G., Rigal-Huguet F., Roboz G. J., Rousselot P., Sanchez-Guijo F. M., Sanz Santillana G., Schafhausen P., Scheid C., Schmidt S., Specchia G., Steegmann J. L., Stenke L., Hochhaus, A, Gambacorti Passerini, C, Abboud, C, Gjertsen, B, Brummendorf, T, Smith, B, Ernst, T, Giraldo-Castellano, P, Olsson-Stromberg, U, Saussele, S, Bardy-Bouxin, N, Viqueira, A, Leip, E, Russell-Smith, T, Leone, J, Rosti, G, Watts, J, Giles, F, Abruzzese, E, Akard, L, Bosi, A, Cervantes, F, Charbonnier, A, Di Raimondo, F, Etienne, G, Garcia Gutierrez, V, Guerci-Bresler, A, Hjorth-Hansen, H, Karsenti, J, Kelly, K, Le Coutre, P, Martinez Chamorro, C, Oehler, V, Orti Pascual, G, Petzer, A, Pungolino, E, Rege-Cambrin, G, Rigal-Huguet, F, Roboz, G, Rousselot, P, Sanchez-Guijo, F, Sanz Santillana, G, Schafhausen, P, Scheid, C, Schmidt, S, Specchia, G, Steegmann, J, Stenke, L, Hochhaus A., Gambacorti Passerini C., Abboud C., Gjertsen B. T., Brummendorf T. H., Smith B. D., Ernst T., Giraldo-Castellano P., Olsson-Stromberg U., Saussele S., Bardy-Bouxin N., Viqueira A., Leip E., Russell-Smith T. A., Leone J., Rosti G., Watts J., Giles F. J., Abruzzese E., Akard L. P., Bosi A., Cervantes F., Charbonnier A., Di Raimondo F., Etienne G., Garcia Gutierrez V., Guerci-Bresler A. P., Hjorth-Hansen H., Karsenti J. M., Kelly K. R., Le Coutre P., Martinez Chamorro C., Oehler V. G., Orti Pascual G., Petzer A., Pungolino E., Rege-Cambrin G., Rigal-Huguet F., Roboz G. J., Rousselot P., Sanchez-Guijo F. M., Sanz Santillana G., Schafhausen P., Scheid C., Schmidt S., Specchia G., Steegmann J. L., and Stenke L.

Abstract

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.

Published
2020

9. Treatment patterns in patients with chronic-phase chronic myeloid leukaemia in routine clinical practice: The simplicity Italian population

Author

Abruzzese, E, Bosi, A, Breccia, M, D'Adda, M, Renzo, N, Liberati, A, Porrini, R, Orlandi, E, Pane, F, Pungolino, E, Sora, F, Stagno, F, Sen, G, Gentilini, F, De Solda, F, Gambacorti-Passerini, C, Abruzzese E., Bosi A., Breccia M., D'Adda M., Renzo N. D., Liberati A. M., Porrini R., Orlandi E. M., Pane F., Pungolino E., Sora F., Stagno F., Sen G. P., Gentilini F., De Solda F., Gambacorti-Passerini C., Abruzzese, E, Bosi, A, Breccia, M, D'Adda, M, Renzo, N, Liberati, A, Porrini, R, Orlandi, E, Pane, F, Pungolino, E, Sora, F, Stagno, F, Sen, G, Gentilini, F, De Solda, F, Gambacorti-Passerini, C, Abruzzese E., Bosi A., Breccia M., D'Adda M., Renzo N. D., Liberati A. M., Porrini R., Orlandi E. M., Pane F., Pungolino E., Sora F., Stagno F., Sen G. P., Gentilini F., De Solda F., and Gambacorti-Passerini C.

Abstract

Background and Objectives: While tyrosine kinase inhibitors (TKIs) have transformed CP-CML management, limited data exist on their use in clinical practice. Methods: SIMPLICITY (NCT01244750) is an observational study in CP-CML patients, exploring first-line (1L) TKI use and management patterns in the US and Europe. Over half of the patients recruited in Europe are from Italy (n=266). This is an analysis of the Italian cohort and a comparison with the rest of the European SIMPLICITY population. Baseline demographic, factors influencing the choice of first-line TKI, response monitoring patterns and predictors of monitoring, and treatment interruptions, discontinuations and switching by index TKIs are presented for the Italian cohort in the first year of treatment and compared with that for the overall European SIMPLICITY cohort. Results: Italian patients received 1L imatinib (IM; retrospective [(n=31]; prospective [n=106]), dasatinib (DAS; n=56) or nilotinib (NIL; n=73). Documented cytogenetic response monitoring by 12 months was lower than expected, but almost all patients had documented molecular response monitoring. Fewer patients discontinued first-line TKI by 12 months in Italy compared with the rest of the European SIMPLICITY population (p=0.003). Of those with ≥12 months follow-up since the start of 1L TKI, only 7.1% (n=19) of Italian patients switched to a second-line TKI, a third less than in the rest of the European SIMPLICITY population. Of interest, intolerance as opposed to resistance, was the main reason for switching. Conclusions: This analysis provides valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice.

Published
2019

10. PH plus STEM CELLS (SCS) IN CHRONIC MYELOID LEUKEMIA (CML): TO ERADICATE OR NOT TO ERADICATE, THIS IS THE QUESTION

Author

Pungolino, E, D'Adda, M, Trojani, A, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Bossi, L, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Pioltelli, M, Rossi, G, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Bossi LE, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro MC, Di Camillo B, Gramegna D, Pioltelli ML, Rossi G, Morra E, Cairoli R, Pungolino, E, D'Adda, M, Trojani, A, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Bossi, L, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Pioltelli, M, Rossi, G, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Bossi LE, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro MC, Di Camillo B, Gramegna D, Pioltelli ML, Rossi G, Morra E, and Cairoli R

Published
2019

11. IDENTIFICAZIONE DI MIRNA E GENI TARGET NELL’ANALISI TRASCRITTOMICA DELLE CELLULE CD34+/LIN- DI PAZIENTI CON LEUCEMIA MIELOIDE CRONICA IN FASE CRONICA DOPO 12 MESI DI TERAPIA CON NILOTINIB

Author

Trojani, A, Pungolino, E, Dal Molin, A, Bossi, L, Rossi, G, D'Adda, M, Perego, A, Elena, C, Turrini, M, Borin, L, Bucelli, C, Malato, S, Carraro, M, Spina, F, Latargia, M, Artale, S, Spedini, P, Anghilieri, M, Di Camillo, B, Baruzzo, G, De Canal, G, Iurlo, A, Morra, E, Cairoli, R, Trojani A, Pungolino E, Dal Molin A, Bossi LE, Rossi G, D'Adda M, Perego A, Elena C, Turrini M, Borin L, Bucelli C, Malato S, Carraro MC, Spina F, Latargia ML, Artale S, Spedini P, Anghilieri M, Di Camillo B, Baruzzo G, De Canal G, Iurlo A, Morra E, Cairoli R, Trojani, A, Pungolino, E, Dal Molin, A, Bossi, L, Rossi, G, D'Adda, M, Perego, A, Elena, C, Turrini, M, Borin, L, Bucelli, C, Malato, S, Carraro, M, Spina, F, Latargia, M, Artale, S, Spedini, P, Anghilieri, M, Di Camillo, B, Baruzzo, G, De Canal, G, Iurlo, A, Morra, E, Cairoli, R, Trojani A, Pungolino E, Dal Molin A, Bossi LE, Rossi G, D'Adda M, Perego A, Elena C, Turrini M, Borin L, Bucelli C, Malato S, Carraro MC, Spina F, Latargia ML, Artale S, Spedini P, Anghilieri M, Di Camillo B, Baruzzo G, De Canal G, Iurlo A, Morra E, and Cairoli R

Published
2019

12. Progressive Down Regulation of JAK-STAT, Cell Cycle, and ABC Transporter Genes in CD34+/Lin- Cells of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients at Diagnosis Vs. 12 Months of Nilotinib Treatment Vs. Healthy Subjects

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Bossi, L, Baruzzo, G, Di Camillo, B, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Bossi L.E., Baruzzo G., Di Camillo B., Perego A., Turrini M., Elena C., Borin L.M., Iurlo A., Malato S., Spina F., Latargia M.L., Spedini P., Artale S., Anghilieri M., Carraro M.C., Bucelli C., De Canal G., Morra E., Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Bossi, L, Baruzzo, G, Di Camillo, B, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Bossi L.E., Baruzzo G., Di Camillo B., Perego A., Turrini M., Elena C., Borin L.M., Iurlo A., Malato S., Spina F., Latargia M.L., Spedini P., Artale S., Anghilieri M., Carraro M.C., Bucelli C., De Canal G., Morra E., and Cairoli R

Published
2019

13. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

Author

Baccarani, M, Castagnetti, F, Gugliotta, G, Rosti, G, Soverini, S, Albeer, A, Pfirrmann, M, Bekadja, Ma, Entasoltan, B, Nachi, M, Elghandour, A, El Sorady, M, Abdelfattah, R, El Nahass, Y, Samra, M, Azzazi, M, Elsobki, E, Moussa, M, Fahmy, O, Mattar, M, Shehata, Azmy, Se, (Azmy, E, 9 ), Emad), Bolarinwa, (Bolarinwa, Ra, ( 10 ), Rahman A., Eid, (Eid, S, Samir)( 11, ), Khelif, (Khelif, A, Abderrhaim)( 11, ), Hached, (Hached, F, Farhat)( 11, ), Menif, (Menif, S, Samia)( 12, ), Rahman, (Rahman, H, Hafizur)( 13, ), Huang, (Huang, Xj, Xiaojun)(, 14, 15, ), Jiang, (Jiang, Q, Qian)(, 14, (Ye, Yx, Yuanxin)( 16, ), Zhu, (Zhu, Hl, Huanling)( 16, ), Chen, (Chen, Sn, Suning)( 17, ), Varma, (Varma, N, Neelam)( 18, ), Ganesan, (Ganesan, P, Prasanth)( 19, ), Gundeti, (Gundeti, S, Sadashivudu)( 20, ), Malhotra, (Malhotra, H, Hemant)( 21, ), Radhakrishnan, (Radhakrishnan, Vs, ( 22 ), Vivek S., Kumar, (Kumar, L, Lalit)( 23, ), Sharawat, (Sharawat, Sk, Surender Kumar)( 23, ), Seth, (Seth, T, Tulika)( 24, ), Ausekar, (Ausekar, Bv, ( 25 ), B. V., Balasubramanian, (Balasubramanian, P, Poonkuzhali)( 26, ), Poopak, (Poopak, B, Behzad)(, 27, 28, ), Inokuchi, (Inokuchi, K, Koiti)( 29, ), Kim, (Kim, Dw, Dong-Wook)( 30, ), Kindi, Al, S (Al Kindi, Salam)( 31, ), Mirasol, (Mirasol, A, Angelina)( 32, ), Qari, (Qari, M, Mohammed)( 33, ), Goh, (Goh, Yt, Yeow Tee)( 34, ), Shih, (Shih, Ly, Lee-Yung)(, 35, 36, ), Branford, (Branford, S, Susan)(, 37, 38, ), Lion, (Lion, T, Thomas)( 39, ), Valent, (Valent, P, Peter)( 40, ), Burgstaller, (Burgstaller, S, Sonja)( 41, ), Thaler, (Thaler, J, Joseph)( 41, ), Labar, (Labar, B, Boris)( 42, ), Zadro, (Zadro, R, Renata)( 42, ), Mayer, (Mayer, J, Jiri)(, 43, 44, ), Zackova, (Zackova, D, Daniela)(, 43, Faber, (Faber, E, Edgar)( 45, ), Pallisgaard, (Pallisgaard, N, Niels)( 46, ), Xavier-Mahon, (Xavier-Mahon, F, Francois)( 47, ), Lippert, (Lippert, E, Eric)( 48, ), Cayuela, (Cayuela, Jm, Jean Michel)( 49, ), Rea, (Rea, D, Delphine)( 49, ), Millot, (Millot, F, Frederic)( 50, ), Suttorp, (Suttorp, M, Meinolf)( 51, ), Hochhaus, (Hochhaus, A, Andreas)( 52, ), Niederwieser, (Niederwieser, D, Dietger)( 53, ), Saussele, (Saussele, S, Susanne)( 54, ), Haferlach, (Haferlach, T, Torsten)( 55, ), Jeromine, (Jeromine, S, Sabine)( 55, ), Panayiotidis, (Panayiotidis, P, Panayiotis)(, 56, 57, ), Conneally, (Conneally, E, Eibhlin)( 58, ), Langabeer, (Langabeer, S, Steve)( 58, ), Nagler, (Nagler, A, Arnon)(, 59, 60, ), Rupoli, (Rupoli, S, Serena)( 61, ), Santoro, (Santoro, N, Nicola)( 62, ), Albano, (Albano, F, Francesco)( 63, ), Castagnetti, (Castagnetti, F, Fausto), Ottaviani, (Ottaviani, E, Emanuela)(, 64, 65, ), Rambaldi, (Rambaldi, A, Alessandro)(, 66, 67, ), Stagno, (Stagno, F, Fabio)( 68, ), Molica, (Molica, S, Stefano)( 69, ), Biagiotti, (Biagiotti, C, Caterina)( 70, ), Scappini, (Scappini, B, Barbara)( 70, ), Lemoli, (Lemoli, R, Roberto)( 71, ), Iurlo, (Iurlo, A, Alessandra)(, 72, 73, ), Pungolino, (Pungolino, E, Ester)( 74, ), Menna, (Menna, G, Giuseppe), Pane, (Pane, F, Fabrizio)( 76, ), Gottardi, (Gottardi, E, Enrico)(, 77, 78, ), Rege-Cambrin, (Rege-Cambrin, G, Giovanna)(, 77, Binotto, (Binotto, G, Gianni)( 79, ), Putti, (Putti, Mc, Maria Caterina)( 80, ), Falzetti, (Falzetti, F, Franca)( 81, ), Visani, (Visani, G, Giuseppe)( 82, ), Galimberti, (Galimberti, S, Sara)( 83, ), Musto, (Musto, P, Pellegrino)( 84, ), Abruzzese, (Abruzzese, E, Elisabetta)( 85, ), Breccia, (Breccia, M, Massimo)( 86, ), Giona, (Giona, F, Fiorina)( 86, ), Chiusolo, (Chiusolo, P, Patrizia)( 87, ), Sica, (Sica, S, Simona)( 87, ), Fava, (Fava, C, Carmen)( 88, ), Ferrero, (Ferrero, D, Dario)( 88, ), Tiribelli, (Tiribelli, M, Mario)( 89, ), Bonifacio, (Bonifacio, M, Massimiliano)( 90, ), Griskevicius, (Griskevicius, L, Laimonas)( 91, ), Musteata, (Musteata, V, Vasile)( 92, ), Janssen, (Janssen, J, Jeroen)( 93, ), Prejzner, (Prejzner, W, Witold)( 94, ), Sacha, (Sacha, T, Tomasz)( 95, ), Waclaw, (Waclaw, J, Joanna)( 95, ), Almeida, (Almeida, Am, Antonio Medina)( 96, ), Kulikov, (Kulikov, S, Sergei)( 97, ), Turkina, (Turkina, A, Anna)( 97, ), Bogdanovic, (Bogdanovic, A, Andrija)( 98, ), Zupan, (Zupan, I, Irena)( 99, ), Marce, (Marce, S, Silvia)( 100, ), Cervantes, (Cervantes, F, Francisco)( 101, ), Steegmann, (Steegmann, Jl, Juan Luis)( 102, ), Kotlyarchuk, (Kotlyarchuk, K, Konstyantyn)( 103, ), Milner, (Milner, Bj, ( 104 ), Benedict J., Rose, (Rose, S, Susan)( 105, ), Clench, (Clench, T, Tim)( 106, ), Waits, (Waits, P, Paula)( 107, ), Austin, (Austin, S, Steve)( 108, ), Wickham, (Wickham, C, Caroline)( 109, ), Clark, (Clark, R, Richard)( 110, ), Apperley, (Apperley, J, Jane), Claudiani, (Claudiani, S, Simone)( 111, ), Foroni, (Foroni, L, Letizia)( 111, ), Szydlo, (Szydlo, R, Richard)( 111, ), Burt, (Burt, E, Emma)( 112, ), Bescoby, (Bescoby, R, Ruth)( 113, ), Cork, (Cork, L, Leanne)( 113, ), O'Brien, (O'Brien, S, Stephen)( 113, ), Green, (Green, B, Bethaney)( 114, ), Hawtree, (Hawtree, S, Sarah)( 114, ), Watson, (Watson, M, Mark)( 114, ), Bengio, (Bengio, Rm, Raquel Maria)( 115, ), Larripa, (Larripa, I, Irene)( 115, ), Pavlovsky, (Pavlovsky, C, Carolina)( 116, ), Moiraghi, (Moiraghi, B, Beatriz)( 117, ), Pinna, De, CAR (Requiao de Pinna, Cristiane Almeida)( 118, ), Magalhaes, GHR (Romani Magalhaes, Gustavo Henrique)( 119, ), Pagnano, (Pagnano, K, Katia)( 120, ), Funke, (Funke, V, Vaneuza)( 121, ), Tavares, (Tavares, Rs, Renato Sampaio)( 122, ), Prado, (Prado, A, Adriana)( 123, ), Azevedo, (Azevedo, Aa, Alita Andrade)( 124, ), Fogliatto, (Fogliatto, L, Laura)( 125, ), Bonecker, (Bonecker, S, Simone)( 126, ), Centrone, (Centrone, R, Renato)( 127, ), Moellman, (Moellman, A, Artur)( 128, ), Conchon, (Conchon, M, Monika)( 130, ), Centurion, (Centurion, Me, Maria Elida)( 131, ), (Prado, Ai, Ana-Ines)( 132, ), Lopez, (Lopez, Jl, ( 133 ), J. L., Petruzziello, (Petruzziello, F, Fara)( 75, ), Bendit, (Bendit, I, Israel), Baccarani M., Castagnetti F., Gugliotta G., Rosti G., Soverini S., Albeer A., and Pfirrmann M.

Subjects
Male, 0301 basic medicine, Cancer Research, bcr-abl, Fusion Proteins, bcr-abl, Global Health, 0302 clinical medicine, hemic and lymphatic diseases, 80 and over, Odds Ratio, Prevalence, Age Factor, Chronic, Young adult, Child, MOLECULAR RESPONSE, Leukemic, Aged, 80 and over, Leukemia, Hematology, Gene Expression Regulation, Leukemic, CHRONIC MYELOGENOUS LEUKEMIA, Age Factors, Myeloid leukemia, Middle Aged, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Human, Adult, Transcriptional Activation, medicine.medical_specialty, Adolescent, Immunology, IMATINIB MESYLATE, DENDRITIC CELLS, CML PATIENTS, Young Adult, 03 medical and health sciences, Myelogenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, BCR/ABL TRANSCRIPT, Preschool, CYTOGENETIC RESPONSE, Aged, Science & Technology, CHRONIC-PHASE, business.industry, Infant, Newborn, Fusion Proteins, ABL FUSION PROTEINS, P190 BCR-ABL, Infant, 1103 Clinical Sciences, Odds ratio, Newborn, medicine.disease, International BCR-ABL Study Group, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Imatinib mesylate, Gene Expression Regulation, BCR-ABL Positive, business, Chronic myelogenous leukemia
Abstract

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associatedwith gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission.

Published
2019
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14. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study.

Author

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

Abstract

The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500. ng/mL, ~50% were chelation-naive. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether patients were chelation-naive or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p<0.0001). This large dataset prospectively confirms the efficacy and well characterizes the safety profile of deferasirox in MDS. © 2010 Elsevier Ltd.

Published
2021

16. IDENTIFICAZIONE DI MIRNA E GENI TARGET NELL’ANALISI TRASCRITTOMICA DELLE CELLULE CD34+/LIN- DI PAZIENTI CON LEUCEMIA MIELOIDE CRONICA IN FASE CRONICA DOPO 12 MESI DI TERAPIA CON NILOTINIB

Author

Trojani A, Pungolino E, Dal Molin A, Bossi LE, Rossi G, D'Adda M, Perego A, Elena C, Turrini M, Borin L, Bucelli C, Malato S, Carraro MC, Spina F, Latargia ML, Artale S, Spedini P, Anghilieri M, Di Camillo B, Baruzzo G, De Canal G, Iurlo A, Morra E, Cairoli R, Trojani, A, Pungolino, E, Dal Molin, A, Bossi, L, Rossi, G, D'Adda, M, Perego, A, Elena, C, Turrini, M, Borin, L, Bucelli, C, Malato, S, Carraro, M, Spina, F, Latargia, M, Artale, S, Spedini, P, Anghilieri, M, Di Camillo, B, Baruzzo, G, De Canal, G, Iurlo, A, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2019

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

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'Adda M, Lodola M, Di Camillo B, Perego A, Turrini M, Orlandi E, Borin L, Iurlo A, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, De Canal G, Morra E, Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'Adda M, Lodola M, Di Camillo B, Perego A, Turrini M, Orlandi E, Borin L, Iurlo A, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, De Canal G, Morra E, and Cairoli R

Abstract

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

Published
2018

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

Author

Pungolino, E, Rossi, G, De Canal, G, Trojani, A, D'Adda, M, Perego, A, Orlandi, E, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Lodola, M, Artale, S, Anghilieri, M, Spedini, P, Cantoni, S, Di Camillo, B, Morra, E, Cairoli, R, Pungolino E., Rossi G., De Canal G., Trojani A., D'adda M., Perego A., Orlandi E. M., Lunghi F., Turrini M., Borin L., Iurlo A., Latargia M. L., Carraro M. C., Spina F., Lodola M., Artale S., Anghilieri M., Spedini P., Cantoni S., Di Camillo B., Morra E., Cairoli R., Pungolino, E, Rossi, G, De Canal, G, Trojani, A, D'Adda, M, Perego, A, Orlandi, E, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Lodola, M, Artale, S, Anghilieri, M, Spedini, P, Cantoni, S, Di Camillo, B, Morra, E, Cairoli, R, Pungolino E., Rossi G., De Canal G., Trojani A., D'adda M., Perego A., Orlandi E. M., Lunghi F., Turrini M., Borin L., Iurlo A., Latargia M. L., Carraro M. C., Spina F., Lodola M., Artale S., Anghilieri M., Spedini P., Cantoni S., Di Camillo B., Morra E., and Cairoli R.

Published
2018

19. Combining Imatinib-Following-Nilotinib Treatment in First Line Therapy for Chronic Phase Chronic Myeloid Leukemia. Update from the PhilosoPhi34 Study at 24 Months of Follow-up

Author

Pioltelli, M, Pungolino, E, D'Adda, M, Elena, C, Borin, L, Perego, A, Malato, S, Spina, F, Artale, S, Carraro, M, Orofino, N, Anghilieri, M, Farina, M, Latargia, M, Iurlo, A, Trojani, A, Turrini, M, Caramella, M, Spedini, P, Rossi, G, Morra, E, Cairoli, R, Pioltelli ML, Pungolino E, D'adda M, Elena C, Borin LM, Perego A, Malato S, Spina F, Artale S, Carraro M, Orofino N, Anghilieri M, Farina M, Latargia ML, Iurlo A, Trojani A, Turrini M, Caramella M, Spedini P, Rossi G, Morra E, Cairoli R, Pioltelli, M, Pungolino, E, D'Adda, M, Elena, C, Borin, L, Perego, A, Malato, S, Spina, F, Artale, S, Carraro, M, Orofino, N, Anghilieri, M, Farina, M, Latargia, M, Iurlo, A, Trojani, A, Turrini, M, Caramella, M, Spedini, P, Rossi, G, Morra, E, Cairoli, R, Pioltelli ML, Pungolino E, D'adda M, Elena C, Borin LM, Perego A, Malato S, Spina F, Artale S, Carraro M, Orofino N, Anghilieri M, Farina M, Latargia ML, Iurlo A, Trojani A, Turrini M, Caramella M, Spedini P, Rossi G, Morra E, and Cairoli R

Published
2018

20. Identification of genes differently expressed between bone marrow CD34+/LIN-cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs 12 months of first-line nilotinib treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Bucelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Lodola M., Di Camillo B., Perego A., Turrini M., Orlandi E., Borin L., Iurlo A., Bucelli C., Malato S., Spina F., Latargia M.L., Lanza F., Artale S., Anghilieri M., Carraro M.C., De Canal G., Morra E., Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Bucelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Lodola M., Di Camillo B., Perego A., Turrini M., Orlandi E., Borin L., Iurlo A., Bucelli C., Malato S., Spina F., Latargia M.L., Lanza F., Artale S., Anghilieri M., Carraro M.C., De Canal G., Morra E., and Cairoli R

Published
2018

21. Nilotinib Deregulates Cell Cycle Checkpoints, ABC Transporters Genes and JAK-STAT Signaling Pathway of CD34+/Lin- Cells in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients after 12 Months of Treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Dal Molin, A, Baruzzo, G, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Cristina, C, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'adda M, Lodola M, Dal Molin A, Baruzzo G, Perego A, Turrini M, Elena C, Borin LM, Iurlo A, Malato S, Spina F, Latargia ML, Spedini P, Artale S, Anghilieri M, Cristina CM, Bucelli C, De Canal G, Morra E, Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Dal Molin, A, Baruzzo, G, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Cristina, C, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'adda M, Lodola M, Dal Molin A, Baruzzo G, Perego A, Turrini M, Elena C, Borin LM, Iurlo A, Malato S, Spina F, Latargia ML, Spedini P, Artale S, Anghilieri M, Cristina CM, Bucelli C, De Canal G, Morra E, and Cairoli R

Published
2018

22. Jak-2 and Nfkbia Gene Expression Play a Strategic Role in Chronic Myeloid Leukemia (CML) Molecular Response during Early Nilotinib Treatment: The PhilosoPhi34 Data

Author

Pungolino, E, D'Adda, M, Trojani, A, Perego, D, Pioltelli, M, Rossi, G, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Lodola, M, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego D, Pioltelli ML, Rossi G, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Lodola M, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro M, Di Camillo B, Gramegna D, Morra E, Cairoli R, Pungolino, E, D'Adda, M, Trojani, A, Perego, D, Pioltelli, M, Rossi, G, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Lodola, M, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego D, Pioltelli ML, Rossi G, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Lodola M, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro M, Di Camillo B, Gramegna D, Morra E, and Cairoli R

Published
2018

23. Use of generic imatinib as first-line treatment in patients with chronic myeloid leukemia (CML): the GIMS (Glivec to Imatinib Switch) study

Author

Gemelli, M, Elli, E, Elena, C, Iurlo, A, Intermesoli, T, Maffioli, M, Pungolino, E, Carraro, M, D'Adda, M, Lunghi, F, Anghileri, M, Polverelli, N, Rossi, M, Bacciocchi, M, Bono, E, Bucelli, C, Passamonti, F, Antolini, L, Passerini, C, Gemelli, Maria, Elli, Elena Maria, Elena, Chiara, Iurlo, Alessandra, Intermesoli, Tamara, Maffioli, Margherita, Pungolino, Ester, Carraro, Maria Cristina, D'Adda, Mariella, Lunghi, Francesca, Anghileri, Michela, Polverelli, Nicola, Rossi, Marianna, Bacciocchi, Mattia, Bono, Elisa, Bucelli, Cristina, Passamonti, Francesco, Antolini, Laura, Passerini, Carlo Gambacorti, Gemelli, M, Elli, E, Elena, C, Iurlo, A, Intermesoli, T, Maffioli, M, Pungolino, E, Carraro, M, D'Adda, M, Lunghi, F, Anghileri, M, Polverelli, N, Rossi, M, Bacciocchi, M, Bono, E, Bucelli, C, Passamonti, F, Antolini, L, Passerini, C, Gemelli, Maria, Elli, Elena Maria, Elena, Chiara, Iurlo, Alessandra, Intermesoli, Tamara, Maffioli, Margherita, Pungolino, Ester, Carraro, Maria Cristina, D'Adda, Mariella, Lunghi, Francesca, Anghileri, Michela, Polverelli, Nicola, Rossi, Marianna, Bacciocchi, Mattia, Bono, Elisa, Bucelli, Cristina, Passamonti, Francesco, Antolini, Laura, and Passerini, Carlo Gambacorti

Abstract

Background Generic formulations of imatinib mesylate have been introduced in Western Europe since 2017 to treat patients with chronic myeloid leukemia (CML). However, results on the safety and efficacy of generic formulations are contrasting. The aim of this study was to investigate the safety and efficacy of generic imatinib in CML patients treated in 12 Italian institutes. Methods This is an observational, retro-prospective analysis of patients with CML for whom the treatment was switched from brand to generic imatinib. We analyzed and compared the variation in quantitative PCR values before and after the switch, and the proportion of patients who maintained molecular response after changing from brand to generic imatinib. Adverse events (AEs) were also evaluated. Results Two hundred patients were enrolled. The median PCR value after the switch was reduced by 0.25 compared to the values before the switch. A significant difference was found between median PCR values before and after the switch in favor of generic imatinib (P = 0.003). Molecular responses remained stable in 69.0%, improved in 25.5%, and worsened in 5.5% of patients. AEs were similar in the pre- and post-switch periods; however, a significant difference was found in favor of generic imatinib for muscular cramps (P < 0.0001), periorbital edema (P=0.0028), edema of the limbs (P <0.0001), fatigue (P =0.0482), and diarrhea (P=0.0027). Conclusion Our data indicate that generic imatinib does not have deleterious effects on CML control and present an acceptable safety profile, similar or better than brand imatinib.

Published
2020

24. Autologous and allogeneic bone marrow transplantation in acute myeloid leukemia in first complete remission: an update of the Genoa experience with 159 patients

Author

Carella, A. M., Frassoni, F., van Lint, M. T., Gualandi, F., Occhini, D., Carlier, P., Pollicardo, N., Pungolino, E., Fagioli, F., Santini, G., Congiu, A., Nati, S., Raffo, M. R., Podesta, M., Corvo, R., Vitale, V., Gallamini, A., Pogliani, E. M., Lanzi, E., Bacigalupo, A., and Marmont, A. M.

Published
1992
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25. Identification of genes differently expressed between bone marrow CD34+/LIN-cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs 12 months of first-line nilotinib treatment

Author

Trojani A., Pungolino E., Rossi G., D'Adda M., Lodola M., Di Camillo B., Perego A., Turrini M., Orlandi E., Borin L., Iurlo A., Bucelli C., Malato S., Spina F., Latargia M.L., Lanza F., Artale S., Anghilieri M., Carraro M.C., De Canal G., Morra E., Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Bucelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, and Cairoli, R

Subjects
CML
Published
2018

26. IDENTIFICATION OF MIRNA AND TARGET GENES IN THE TRANSCRIPTOME ANALYSIS OF CD34+/LIN- CELLS OF PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN THE CHRONIC PHASE AFTER 12 MONTHS OF NILOTINIB THERAPY

Author

Trojani, A., Pungolino, E., Dal Molin, A., Luca Emanuele Bossi, Rossi, G., D Adda, M., Perego, A., Elena, C., Turrini, M., Borin, L., Bucelli, C., Malato, S., Carraro, M. C., Spina, F., Latargia, M. L., Artale, S., Spedini, P., Anghilieri, M., Di Camillo, B., Baruzzo, G., Canal, G., Iurlo, A., Morra, E., and Cairoli, R.

Published
2019

27. Gene Expression Profiling and Cellularity of Bone Marrow CD34+/Lin- Cells of Patients with Chronic-Phase Chronic Myeloid Leukemia at Diagnosis Vs. 12 Months of First-Line Nilotinib Treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, EM, Borin, LM, Iurlo, A, Malato, S, Spina, F, Latargia, ML, Lanza, F, Artale, S, Anghilieri, M, Carraro, MC, Bucelli, C, De Canal, G, Morra, E, Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2017

28. Preliminary Experience of Imatinib after Nilotinib in the First Line Treatment of Chronic Myeloid Leukemia

Author

Pungolino, E, D'adda M, Perego A, Orlandi, EM, Turrini, M, Borin, LM, Iurlo, A, Artale, S, Latargia, ML, Anghilieri, M, Malato, S, Trojani, A, Spina, F, Carraro, MC, Pioltelli, ML, Elena, C, Bucelli, C, Spedini, P, Rossi, G, Morra, E, Cairoli, R, Pungolino, E, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Borin, L, Iurlo, A, Artale, S, Latargia, M, Anghilieri, M, Malato, S, Trojani, A, Spina, F, Carraro, M, Pioltelli, M, Elena, C, Bucelli, C, Spedini, P, Rossi, G, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2017

29. Treatment patterns in patients with chronic-phase chronic myeloid leukaemia in routine clinical practice: The simplicity Italian population

Author

Abruzzese, E., Bosi, A., Breccia, M., D'Adda, M., Renzo, N. D., Liberati, A. M., Porrini, R., Orlandi, E. M., Pane, F., Pungolino, E., Sora', Federica, Stagno, F., Sen, G. P., Gentilini, F., De Solda, F., Gambacorti-Passerini, C., Sorà F. (ORCID:0000-0002-9607-5298), Abruzzese, E., Bosi, A., Breccia, M., D'Adda, M., Renzo, N. D., Liberati, A. M., Porrini, R., Orlandi, E. M., Pane, F., Pungolino, E., Sora', Federica, Stagno, F., Sen, G. P., Gentilini, F., De Solda, F., Gambacorti-Passerini, C., and Sorà F. (ORCID:0000-0002-9607-5298)

Abstract

Background and Objectives: While tyrosine kinase inhibitors (TKIs) have transformed CP-CML management, limited data exist on their use in clinical practice. Methods: SIMPLICITY (NCT01244750) is an observational study in CP-CML patients, exploring first-line (1L) TKI use and management patterns in the US and Europe. Over half of the patients recruited in Europe are from Italy (n=266). This is an analysis of the Italian cohort and a comparison with the rest of the European SIMPLICITY population. Baseline demographic, factors influencing the choice of first-line TKI, response monitoring patterns and predictors of monitoring, and treatment interruptions, discontinuations and switching by index TKIs are presented for the Italian cohort in the first year of treatment and compared with that for the overall European SIMPLICITY cohort. Results: Italian patients received 1L imatinib (IM; retrospective [(n=31]; prospective [n=106]), dasatinib (DAS; n=56) or nilotinib (NIL; n=73). Documented cytogenetic response monitoring by 12 months was lower than expected, but almost all patients had documented molecular response monitoring. Fewer patients discontinued first-line TKI by 12 months in Italy compared with the rest of the European SIMPLICITY population (p=0.003). Of those with ≥12 months follow-up since the start of 1L TKI, only 7.1% (n=19) of Italian patients switched to a second-line TKI, a third less than in the rest of the European SIMPLICITY population. Of interest, intolerance as opposed to resistance, was the main reason for switching. Conclusions: This analysis provides valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice.

Published
2019

30. DIFFERENT SETS OF GENES WERE ASSOCIATED TO THE MOLECULAR RESPONSE AFTER 3 AND 6 MONTHS OF FIRST-LINE NILOTINIB TREATMENT BY MICROARRAY OF CD34+/LIN- CELLS OF CHRONIC PHASE CML PATIENTS AT DIAGNOSIS

Author

Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Orlandi, E, Elena, C, Iurlo, A, Bucelli, C, Borin, L, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bertinato, E, Morra, E, Cairoli, R, Trojani A, Pungolino E, Lodola M, Di Camillo B, D'Adda M, Perego A, Turrini M, Orlandi E, Elena C, Iurlo A, Bucelli C, Borin L, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, Bertinato E, Morra E, Cairoli R, Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Orlandi, E, Elena, C, Iurlo, A, Bucelli, C, Borin, L, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bertinato, E, Morra, E, Cairoli, R, Trojani A, Pungolino E, Lodola M, Di Camillo B, D'Adda M, Perego A, Turrini M, Orlandi E, Elena C, Iurlo A, Bucelli C, Borin L, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, Bertinato E, Morra E, and Cairoli R

Published
2016

31. Jak-2 and Nfkbia Gene Expression Play a Strategic Role in Chronic Myeloid Leukemia (CML) Molecular Response during Early Nilotinib Treatment: The PhilosoPhi34 Data

Author

Pungolino E, D'adda M, Trojani A, Perego D, Pioltelli ML, Rossi G, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Lodola M, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro M, Di Camillo B, Gramegna D, Morra E, Cairoli R, Pungolino, E, D'Adda, M, Trojani, A, Perego, D, Pioltelli, M, Rossi, G, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Lodola, M, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Morra, E, and Cairoli, R

Subjects
Janus kinase 2, biology, business.industry, Immunology, NFKBIA Gene, Myeloid leukemia, Cell Biology, Hematology, NFKB1, Biochemistry, Gene expression profiling, medicine.anatomical_structure, Nilotinib, Molecular Response, Cancer research, biology.protein, Medicine, Bone marrow, business, medicine.drug
Abstract

Background Targeted therapy with Tyrosine-Kinase-Inhibitors (TKIs) totally modified the course of treatment of Chronic Myeloid Leukemia (CML). The objectives and the needs of treatment have been modified during the last years and the discontinuation of therapy is now a feasible aim. However, a lot of biological data acquired in the last twenty years, showed that degree and mechanisms of Leukemic Stem Cells (LSCs) clearance during TKI treatment are not clearly established as well as the predictive criteria for a stable and prolonged Treatment Free Remission (TFR). The multicentre, prospective, single-arm PhilosoPhi34 study (EudraCT: 2012-005062-34) was designed by the Rete Ematologica Lombarda (REL), to verify the in-vivo activity and time-course of first-line Nilotinib (NIL) therapy on Bone Marrow (BM) CD34+/lin-Ph+ cells clearance. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin- cells at diagnosis and at 12 months (mos) of treatment, for the first 30 evaluable pts, was included. Preliminary GEP data suggested a correlation between different NFKBIA expression at diagnosis and at 12 mos and the achievement of a deeper Molecular Response (MR) (Pungolino et al, AJH 2018). We report here some results of GEP analysis on all enrolled evaluable pts and their possible correlation with clinical data. Methods BM cells were collected and stored at diagnosis and at 12 mos of treatment. CD34+/lin- cells were purified with a Diamond CD34 Isolation Kit Miltenyi (97% of purity). For GEP analysis we used Affymetrix HG-U133 Plus 2.0 microarray and Genechip platform (Affymetrix) and the Affymetrix GeneChip Scanner 3000. Data was pre-processed and normalized using the Robust Multi-array Average (RMA) algorithm. The Significant Analysis of Microarrays (SAM) was used to identify genes with statistically significant changes in expression. P-values were corrected for multiple testing using false discovery rate, for differentially expressed genes confirmation. We chose to analyse different expression of NFKBIA (the inhibitor of NF-kB onco-gene) in order to confirm the preliminary data reported on the first 30 analysed pts. Pts were monitored according to ELN-recommendation. Biological data were correlated with MR at 3, 12 and 36 mos of therapy. We use Fishers test to compare unbalanced group. Results Out of the 87 enrolled pts, 80 completed the first 12 mos of treatment and 78 (1 failure and 77 CCyR) were evaluable for GEP analysis. We observed 2726 genes symbol differentially expressed of which 1868 are coding genes. Among these, JAK-2 showed a down regulation at 12 mos (p: .024). JAK-2 expression ranged from 2.62 to 4.95 at diagnosis and from 1.48 to 5.58 at 12 mos. Only 26/78 pts increased JAK-2 expression that was > 4 in 1/26 pts, at diagnosis; 2/26 (7.69%) pts showed a H Sokal. Other 52/78 pts decreased JAK-2 expression that was ≥ 4 in 21/52 pts, at diagnosis; 10/52 (19.23%) pts and 6/21 (28,57%) pts showed a H Sokal. Similarly, when we compared low JAK-2 expression (< 3.5) vs vary high expression (≥ 4) 2/21 vs 6/22 pts had H Sokal (9.52% vs 27.27%; p: .0057). Considering the role of JAK-2 and NFKBIA in cell regulation and survival, we evaluated how the combination of their different expression impact on MR (i.e. NFKBIA increased expression/JAK-2 decreased expression vs NFKBIA decreased expression/JAK-2 increased expression). Data are reported in Table 1 and 2. Conclusion GEP analysis showed a down regulation of JAK-2 expression after 12 mos of first line NIL treatment, in 78 early chronic phase CML pts. Data suggest that high expression of JAK-2, at diagnosis, correlate with H Sokal score. However, H Sokal pts with a JAK-2 down regulation, obtain during treatment similar MR compared to L Sokal pts. Additionally, the study confirms our preliminary observation on 30 pts , concerning the role of NKBIA up - regulation in increasing percentage of earlier and deeper MR . The better condition of NFKBIA and JAK-2 expression (up regulation of NFKBIA and down regulation of JAK-2) is associated with a higher percentage of early MR3 and optimal responses over time, despite the higher number of H Sokal pts in this group. A study with NIL as first line treatment combined with low dose of JAK-2 inhibitor and a natural inhibitor of NF-kB (such as curcuma), during the first year of treatment, to increase the deeper MR rate and the probability of TFR is warrented. Disclosures Rossi: Sandoz: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Teva: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Novartis: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Published
2018
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32. DIFFERENT SETS OF GENES WERE ASSOCIATED TO THE MOLECULAR RESPONSE AFTER 3 AND 6 MONTHS OF FIRST-LINE NILOTINIB TREATMENT BY MICROARRAY OF CD34+/LIN- CELLS OF CHRONIC PHASE CML PATIENTS AT DIAGNOSIS

Author

Trojani A, Pungolino E, Lodola M, Di Camillo B, D'Adda M, Perego A, Turrini M, Orlandi E, Elena C, Iurlo A, Bucelli C, Borin L, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, Bertinato E, Morra E, Cairoli R, Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Orlandi, E, Elena, C, Iurlo, A, Bucelli, C, Borin, L, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bertinato, E, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2016

33. REL-PROTOCOL PHILOSOPHI34 CONFIRMS THAT NILOTINIB RAPIDLY INDUCES CD34+/LIN-PH+ CELLS DISAPPEARANCE IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA (CML) IN CHRONIC PHASE (CP)

Author

Pungolino, E, De Canal, G, D'Adda, M, Perego, A, Orlandi, EM, Turrini, M, Trojani, A, Malato, S, Lodola, M, Borin, L, Iurlo, A, Artale, S, Spina, F, Pioltelli, ML, Latargia, ML, Brusorio, S, Elena, C, Lanza, F, Anghilieri, M, Carraro, MC, Rossi, G, Morra, E, Cairoli, R, Pungolino, E, De Canal, G, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Trojani, A, Malato, S, Lodola, M, Borin, L, Iurlo, A, Artale, S, Spina, F, Pioltelli, M, Latargia, M, Brusorio, S, Elena, C, Lanza, F, Anghilieri, M, Carraro, M, Rossi, G, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2016

35. Gene Expression Profiling of CD34+/Lin- Cells of Patients with Chronic Myeloid Leukemia at Diagnosis and after 12 Months of Nilotinib

Author

Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Artale, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Artale S, Morra E, Pungolino E, Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Artale, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Artale S, Morra E, and Pungolino E

Published
2014

36. GENE EXPRESSION PROFILING OF CD34+/LIN- CELLS OF PATIENTS WITH CHRONIC MYELOID LEUKEMIA AT DIAGNOSIS IDENTIFIES NEW GENES RELATED TO THE NUMBER OF CD34+/LIN- CELLS DURING NILOTINIB TREATMENT

Author

Trojani, A, Lodola, M, Di Camillo, B, Capucci, A, Cavalli, L, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Capucci A, Cavalli L, Perego A, Pogliani E, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, Pungolino E, Trojani, A, Lodola, M, Di Camillo, B, Capucci, A, Cavalli, L, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Capucci A, Cavalli L, Perego A, Pogliani E, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, and Pungolino E

Published
2014

37. Microarray of Bone Marrow CD34+/Lin- Cells from Patients with Chronic Myeloid Leukemia (CML)

Author

Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, Pungolino E, Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, and Pungolino E

Published
2014

38. GENE EXPRESSION PROFILING OF CD34+/LIN- CELLS OF PATIENTS WITH CHRONIC MYELOID LEUKEMIA AT DIAGNOSIS IDENTIFIES NEW GENES RELATED TO THE NUMBER OF CD34+/LIN- CELLS DURING NILOTINIB TREATMENT

Author

Trojani A, Lodola M, Di Camillo B, Capucci A, Cavalli L, Perego A, Pogliani E, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, Pungolino E, Trojani, A, Lodola, M, Di Camillo, B, Capucci, A, Cavalli, L, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, and Pungolino, E

Subjects
hepatology
Published
2014

39. Pleural effusion and molecular response in dasatinib-treated chronic myeloid leukemia patients in a real-life Italian multicenter series.

Author

Iurlo, A, Galimberti, S, Abruzzese, E, Annunziata, M, Bonifacio, M, Latagliata, R, Pregno, P, Ferrero, D, Sora', Federica, Orlandi, Em, Fava, Chiara, Cattaneo, Davide, Bucelli CBinotto, G, Pungolino, E, Tiribelli, M, Gozzini, A, Gugliotta, G, Castagnetti, F, Stagno, F, Rege-Cambrin, G, Martino, B, Luciano, L, Breccia, M, Sica, Simona, Bocchia, M, Pane, F, Saglio, G, Rosti, G, Specchia, G, Cortelezzi, A, Baccarani, M, Sorà F (ORCID:0000-0002-9607-5298), Sica S (ORCID:0000-0003-2426-3465), Iurlo, A, Galimberti, S, Abruzzese, E, Annunziata, M, Bonifacio, M, Latagliata, R, Pregno, P, Ferrero, D, Sora', Federica, Orlandi, Em, Fava, Chiara, Cattaneo, Davide, Bucelli CBinotto, G, Pungolino, E, Tiribelli, M, Gozzini, A, Gugliotta, G, Castagnetti, F, Stagno, F, Rege-Cambrin, G, Martino, B, Luciano, L, Breccia, M, Sica, Simona, Bocchia, M, Pane, F, Saglio, G, Rosti, G, Specchia, G, Cortelezzi, A, Baccarani, M, Sorà F (ORCID:0000-0002-9607-5298), and Sica S (ORCID:0000-0003-2426-3465)

Abstract

Pleural effusion (PE) represents the leading cause of dasatinib (DAS) discontinuation. However, the pathogenic mechanism of this adverse event (AE) is unknown and its management unclear. We investigated if a DAS dose reduction after the first PE would prevent the recurrence of this AE. We retrospectively collected data on all the cases of PE in CML-chronic phase (CP) DAS-treated patients from November 2005 to February 2017 in 21 Italian hematological centers. We identified 196 cases of PE in a series of 853 CML-CP DAS-treated patients (incidence 23.0%). DAS starting dose was 100 mg/day in 70.4% of patients, less than 100 mg/day in 14.3%, and more than 100 mg/day in the remaining cases. Median time from DAS start to PE was 16.6 months. At first PE development, 28.6% of patients were in MMR, and 37.8% in deep molecular response (DMR). DAS was temporary interrupted in 71.9% of cases, with a dose reduction in 59.2%. Recurrence was observed in 59.4% of the cases. Treatment was definitively discontinued due to PE in 29.1% of the cases. Interestingly, among patients whose DAS dosage was reduced, 59.5% experienced PE recurrence. DAS dose reduction after the first episode of PE did not prevent recurrence of this AE. Therefore, once a MMR or a DMR is achieved, different strategies of DAS dose management can be proposed prior to the development of PE, such as daily dose reduction or, as an alternative option, an on/off treatment with a weekend drug holiday.

Published
2017

40. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

Author

Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM, Moiraghi B, Perez M, Greil R, Valent P, Bosly A, Martiat P, Noens L, André M, Verhoef G, Conchon M, Souza C, Nonino A, Hungria V, Zanichelli MA, Colturato V, Forrest D, Lipton JH, Savoie ML, Delage R, Lalancette M, Quintero G, Gomez M, Klamova H, Faber E, Bjerrum OW, Fredriksen H, Vestergaard H, Marcher C, Kamel H, Elzawam H, Porkka K, Remes K, Reiffers J, Guilhot F, Facon T, Tulliez M, Guerci Bresler AP, Nicolini FE, Charbonnier A, Rea D, Johnson Ansah A, Legros L, Harousseau JL, Rigal Huguet F, Escoffre M, Gardembas M, Guyotat D, Cahn JY, Gattermann N, Ottmann O, Niederwieser D, Stegelmann F, Schafhausen P, Brümmendorf T, Duyster J, Blumenstengel K, Scheid C, Kneba M, Kwong YL, Masszi T, Petrini M, Alimena G, Di Raimondo F, Rosti G, Rotoli B, Pungolino E, Amadori S, Abruzzese E, Fioritoni G, Lauria F, Bosi A, Martelli M, Rambaldi A, Ferrara F, Nobile F, Gobbi M, Carella AM, Orlandi EM, Leoni P, Tiribelli M, Levis A, Imamura M, Takahashi N, Tsukamoto N, Chiba S, Nagai T, Okamoto S, Miura O, Kurokawa M, Ohnishi K, Toba K, Nakao S, Tomita A, Miyamura K, Hino M, Maeda Y, Kimura A, Kawaguchi T, Miyazaki Y, Nakaseko C, Jinnai I, Matsuda A, Matsumura I, Ishikawa J, Ohyashiki K, Okada M, Usuki K, Kobayashi Y, Ohishi K, Imai K, Miyawaki S, Kanda Y, Park SY, Kim HJ, Sohn SK, Lee KH, Jung CW, Ong TC, Gómez Almaguer D, Kassack J, Ossenkoppele GJ, Gedde Dahl T, Hjorth Hansen H, Jedrzejczak W, Dmoszynska A, Starzak Dwozdz J, Holowiecki J, Kyrcz Krzemieñ S, Kuliczkowski K, Zaritsky A, Turkina A, Pospelova T, Goh YT, Koh LP, Demitrovicova L, Mistrik M, Ruff P, Louw V, Dreosti LM, Novitzky N, Cohen G, Cervantes F, Cañizo C, de Paz R, del Castillo S, Perez Encinas M, Sanz Alonso M, Marin F, Pérez López R, Hernandez Boluda J, Echeveste Gutierrez MA, Odriozola J, Herrera P, Steegman JL, Conde E, Lopez P, Giraldo P, Boque C, Heredia B, Font AJ, Rodriguez RF, Rodriguez MJ, Batlle J, Stenke L, Lehmann S, Wadenvik H, Simonsson B, Markevärn B, Själander A, Richter J, Bjoreman M, Eriksson KM, Chalandon Y, Shih LY, Yao M, Wang MC, Jootar S, Bunworasate U, Ulkü B, Haznedar R, Undar B, Sahin B, Marin D, Smith G, Byrne J, Holyoake T, Kalaycio M, Akard L, Heaney M, Al Janadi A, Goldberg S, Powell B, Harker WG, Shea T, Gingrich R, Glass J, Paquette R, Siegrist C, Woodson M, Fehrenbacher L, Koh H, Flinn I, Arrowsmith E, Ervin T, Guerra M, Wallach H, Berry W, Burke J, Edenfield W, Guzley G, Davis J, Richards D, Schlossman D, Kolibaba K, Alemany C, Savin M, Robbins G, Lopez J, Goldman JM, Camm J, Schiffer CA, Sargent D.J., PANE, FABRIZIO, Saglio, G, Kim, Dw, Issaragrisil, S, le Coutre, P, Etienne, G, Lobo, C, Pasquini, R, Clark, Re, Hochhaus, A, Hughes, Tp, Gallagher, N, Hoenekopp, A, Dong, M, Haque, A, Larson, Ra, Kantarjian, Hm, Moiraghi, B, Perez, M, Greil, R, Valent, P, Bosly, A, Martiat, P, Noens, L, André, M, Verhoef, G, Conchon, M, Souza, C, Nonino, A, Hungria, V, Zanichelli, Ma, Colturato, V, Forrest, D, Lipton, Jh, Savoie, Ml, Delage, R, Lalancette, M, Quintero, G, Gomez, M, Klamova, H, Faber, E, Bjerrum, Ow, Fredriksen, H, Vestergaard, H, Marcher, C, Kamel, H, Elzawam, H, Porkka, K, Remes, K, Reiffers, J, Guilhot, F, Facon, T, Tulliez, M, Guerci Bresler, Ap, Nicolini, Fe, Charbonnier, A, Rea, D, Johnson Ansah, A, Legros, L, Harousseau, Jl, Rigal Huguet, F, Escoffre, M, Gardembas, M, Guyotat, D, Cahn, Jy, Gattermann, N, Ottmann, O, Niederwieser, D, Stegelmann, F, Schafhausen, P, Brümmendorf, T, Duyster, J, Blumenstengel, K, Scheid, C, Kneba, M, Kwong, Yl, Masszi, T, Petrini, M, Alimena, G, Di Raimondo, F, Rosti, G, Rotoli, B, Pane, Fabrizio, Pungolino, E, Amadori, S, Abruzzese, E, Fioritoni, G, Lauria, F, Bosi, A, Martelli, M, Rambaldi, A, Ferrara, F, Nobile, F, Gobbi, M, Carella, Am, Orlandi, Em, Leoni, P, Tiribelli, M, Levis, A, Imamura, M, Takahashi, N, Tsukamoto, N, Chiba, S, Nagai, T, Okamoto, S, Miura, O, Kurokawa, M, Ohnishi, K, Toba, K, Nakao, S, Tomita, A, Miyamura, K, Hino, M, Maeda, Y, Kimura, A, Kawaguchi, T, Miyazaki, Y, Nakaseko, C, Jinnai, I, Matsuda, A, Matsumura, I, Ishikawa, J, Ohyashiki, K, Okada, M, Usuki, K, Kobayashi, Y, Ohishi, K, Imai, K, Miyawaki, S, Kanda, Y, Park, Sy, Kim, Hj, Sohn, Sk, Lee, Kh, Jung, Cw, Ong, Tc, Gómez Almaguer, D, Kassack, J, Ossenkoppele, Gj, Gedde Dahl, T, Hjorth Hansen, H, Jedrzejczak, W, Dmoszynska, A, Starzak Dwozdz, J, Holowiecki, J, Kyrcz Krzemieñ, S, Kuliczkowski, K, Zaritsky, A, Turkina, A, Pospelova, T, Goh, Yt, Koh, Lp, Demitrovicova, L, Mistrik, M, Ruff, P, Louw, V, Dreosti, Lm, Novitzky, N, Cohen, G, Cervantes, F, Cañizo, C, de Paz, R, del Castillo, S, Perez Encinas, M, Sanz Alonso, M, Marin, F, Pérez López, R, Hernandez Boluda, J, Echeveste Gutierrez, Ma, Odriozola, J, Herrera, P, Steegman, Jl, Conde, E, Lopez, P, Giraldo, P, Boque, C, Heredia, B, Font, Aj, Rodriguez, Rf, Rodriguez, Mj, Batlle, J, Stenke, L, Lehmann, S, Wadenvik, H, Simonsson, B, Markevärn, B, Själander, A, Richter, J, Bjoreman, M, Eriksson, Km, Chalandon, Y, Shih, Ly, Yao, M, Wang, Mc, Jootar, S, Bunworasate, U, Ulkü, B, Haznedar, R, Undar, B, Sahin, B, Marin, D, Smith, G, Byrne, J, Holyoake, T, Kalaycio, M, Akard, L, Heaney, M, Al Janadi, A, Goldberg, S, Powell, B, Harker, Wg, Shea, T, Gingrich, R, Glass, J, Paquette, R, Siegrist, C, Woodson, M, Fehrenbacher, L, Koh, H, Flinn, I, Arrowsmith, E, Ervin, T, Guerra, M, Wallach, H, Berry, W, Burke, J, Edenfield, W, Guzley, G, Davis, J, Richards, D, Schlossman, D, Kolibaba, K, Alemany, C, Savin, M, Robbins, G, Lopez, J, Goldman, Jm, Camm, J, Schiffer, Ca, and Sargent, D. J.

Published
2010

41. LONG TERM OUTCOME OF INTERMITTENT IMATINIB TREATMENT POLICY FOR MANAGINGCHRONIC MYELOID LEUKEMIA IN THE ELDERLY

Author

Russo, Domenico, Malagola, Michele, Skert, C., Cancelli, V., Turri, D., Pregno, P., Pierri, I., Fogli, M., Testoni, N., De Vivo, A., Castagnetti, F., Pungolino, E., Stagno, F., Breccia, M., Martino, B., Intermesoli, T., Rege Cambrin, G., Nicolini, G., Abruzzese, E., Tiribelli, M., Bigazzi, C., Usala, E., Russo, S., Russo Rossi, A., Lunghi, M., Bocchia, M., D’Emilio, A., Santini, V., Girasoli, M., Di Lorenzo, R., Cesana, Bruno Mario, Soverini, S., Martinelli, G., Rosti, G., and Baccarani, M. .

Published
2015

42. 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, Mario, 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. 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, Renato, Pizzolo, G., Meneghini, V., and Rodighiero, F.

Published
2015

43. 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

44. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with Vitamin K antagonists

Author

De Stefano, Valerio, Ruggeri, M., Cervantes, F., Alvarez Larrán, A., Iurlo, A., Randi, M. L., Elli, E., Finazzi, M. C., Finazzi, G., Zetterberg, E., Vianelli, N., Gaidano, G., Rossi, Elena, Betti, Silvia, Nichele, I., Cattaneo, D., Palova, M., Ellis, M. H., Cacciola, R., Tieghi, A., Hernandez Boluda, J. C., Pungolino, E., Specchia, G., Rapezzi, D., Forcina, A., Musolino, C., Carobbio, A., Griesshammer, M., Sant'Antonio, E., Vannucchi, A. M., Barbui, T., De Stefano, Valerio (ORCID:0000-0002-5178-5827), Rossi, Elena (ORCID:0000-0002-7572-9379), De Stefano, Valerio, Ruggeri, M., Cervantes, F., Alvarez Larrán, A., Iurlo, A., Randi, M. L., Elli, E., Finazzi, M. C., Finazzi, G., Zetterberg, E., Vianelli, N., Gaidano, G., Rossi, Elena, Betti, Silvia, Nichele, I., Cattaneo, D., Palova, M., Ellis, M. H., Cacciola, R., Tieghi, A., Hernandez Boluda, J. C., Pungolino, E., Specchia, G., Rapezzi, D., Forcina, A., Musolino, C., Carobbio, A., Griesshammer, M., Sant'Antonio, E., Vannucchi, A. M., Barbui, T., De Stefano, Valerio (ORCID:0000-0002-5178-5827), and Rossi, Elena (ORCID:0000-0002-7572-9379)

Abstract

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.

Published
2016

45. Splanchnic vein thrombosis in myeloproliferative neoplasms: Risk factors for recurrences in a cohort of 181 patients

Author

De Stefano, Valerio, Vannucchi, A. M., Ruggeri, M., Cervantes, F., Alvarez Larrán, A., Iurlo, A., Randi, M. L., Pieri, L., Rossi, Elena, Guglielmelli, P., Betti, Silvia, Elli, E., Finazzi, M. C., Finazzi, G., Zetterberg, E., Vianelli, N., Gaidano, G., Nichele, I., Cattaneo, D., Palova, M., Ellis, M. H., Cacciola, E., Tieghi, A., Hernandez Boluda, J. C., Pungolino, E., Specchia, G., Rapezzi, D., Forcina, A., Musolino, C., Carobbio, A., Griesshammer, M., Barbui, T., De Stefano, Valerio (ORCID:0000-0002-5178-5827), Rossi, Elena (ORCID:0000-0002-7572-9379), De Stefano, Valerio, Vannucchi, A. M., Ruggeri, M., Cervantes, F., Alvarez Larrán, A., Iurlo, A., Randi, M. L., Pieri, L., Rossi, Elena, Guglielmelli, P., Betti, Silvia, Elli, E., Finazzi, M. C., Finazzi, G., Zetterberg, E., Vianelli, N., Gaidano, G., Nichele, I., Cattaneo, D., Palova, M., Ellis, M. H., Cacciola, E., Tieghi, A., Hernandez Boluda, J. C., Pungolino, E., Specchia, G., Rapezzi, D., Forcina, A., Musolino, C., Carobbio, A., Griesshammer, M., Barbui, T., De Stefano, Valerio (ORCID:0000-0002-5178-5827), and Rossi, Elena (ORCID:0000-0002-7572-9379)

Abstract

We retrospectively studied 181 patients with polycythaemia vera (n=67), essential thrombocythaemia (n=67) or primary myelofibrosis (n=47), who presented a first episode of splanchnic vein thrombosis (SVT). Budd-Chiari syndrome (BCS) and portal vein thrombosis were diagnosed in 31 (17.1%) and 109 (60.3%) patients, respectively; isolated thrombosis of the mesenteric or splenic veins was detected in 18 and 23 cases, respectively. After this index event, the patients were followed for 735 patient years (pt-years) and experienced 31 recurrences corresponding to an incidence rate of 4.2 per 100 pt-years. Factors associated with a significantly higher risk of recurrence were BCS (hazard ratio (HR): 3.03), history of previous thrombosis (HR: 3.62), splenomegaly (HR: 2.66) and leukocytosis (HR: 2.8). Vitamin K-antagonists (VKA) were prescribed in 85% of patients and the recurrence rate was 3.9 per 100 pt-years, whereas in the small fraction (15%) not receiving VKA more recurrences (7.2 per 100 pt-years) were reported. Intracranial and extracranial major bleeding was recorded mainly in patients on VKA and the corresponding rate was 2.0 per 100 pt-years. In conclusion, despite anticoagulation treatment, the recurrence rate after SVT in myeloproliferative neoplasms is high and suggests the exploration of new avenues of secondary prophylaxis with new antithrombotic drugs and JAK-2 inhibitors.

Published
2016

46. Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients

Author

De Stefano, V, primary, Vannucchi, A M, additional, Ruggeri, M, additional, Cervantes, F, additional, Alvarez-Larrán, A, additional, Iurlo, A, additional, Randi, M L, additional, Pieri, L, additional, Rossi, E, additional, Guglielmelli, P, additional, Betti, S, additional, Elli, E, additional, Finazzi, M C, additional, Finazzi, G, additional, Zetterberg, E, additional, Vianelli, N, additional, Gaidano, G, additional, Nichele, I, additional, Cattaneo, D, additional, Palova, M, additional, Ellis, M H, additional, Cacciola, E, additional, Tieghi, A, additional, Hernandez-Boluda, J C, additional, Pungolino, E, additional, Specchia, G, additional, Rapezzi, D, additional, Forcina, A, additional, Musolino, C, additional, Carobbio, A, additional, Griesshammer, M, additional, and Barbui, T, additional

Published
2016
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48. Updating Long-Term Outcome of Intermittent Imatinib (INTERIM) Treatment in Elderly Patients with Ph plus -CML

Author

Russo, D, Martinelli, G, Malagola, M, Cancelli, V, Skert, C, Soverini, S, Iacobucci, I, Turri, D, Mirto, S, Gobbi, M, Pierri, I, Vitolo, U, Pregno, P, Fogli, M, Testoni, N, De Vivo, A, Castagnetti, F, Morra, E, Pungolino, E, Di Raimondo, F, Stagno, F, Alimena, G, Breccia, M, Nobile, F, Martino, B, Rambaldi, A, Intermesoli, T, Saglio, G, Cambrin, Gr, Visani, G, Nicolini, G, de Fabritiis, P, Abruzzese, E, Fanin, R, Tiribelli, M, Galieni, P, Bigazzi, C, Specchia, G, Angelucci, E, Usala, E, Musolino, C, Russo, S, Gaidano, G, Lunghi, M, Lauria, F, Bocchia, M, Rodeghiero, F, D'Emilio, A, Bosi, A, Santini, V, Quarta, G, Girasoli, M, Fioritoni, G, Di Lorenzo, R, Cesana, Bm, and Rosti, G

Published
2014

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