9 results on '"Scaffidi, Luigi"'
Search Results
2. Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors.
- Author
-
Mulas O, Caocci G, Stagno F, Bonifacio M, Annunziata M, Luciano L, Orlandi EM, Abruzzese E, Sgherza N, Martino B, Albano F, Galimberti S, Pregno P, Bocchia M, Castagnetti F, Tiribelli M, Binotto G, Gozzini A, Capodanno I, Fozza C, Luzi D, Efficace F, Simula MP, Scaffidi L, De Gregorio F, Elena C, Trawinska MM, Cattaneo D, Attolico I, Baratè C, Pirillo F, Sicuranza A, Gugliotta G, Stella R, Scalzulli E, Iurlo A, Foà R, Breccia M, and La Nasa G
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Drug Therapy, Combination, Female, Humans, Hypertension complications, Hypertension epidemiology, Incidence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Male, Middle Aged, Protein Kinase Inhibitors classification, Renin-Angiotensin System drug effects, Risk Factors, Survival Analysis, Thrombosis prevention & control, Angiotensin Receptor Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Hypertension drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors therapeutic use, Thrombosis epidemiology
- Abstract
Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their additional cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-year cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rd
G TKIs.- Published
- 2020
- Full Text
- View/download PDF
3. Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: the NEXT-in-CML study.
- Author
-
Soverini S, Bavaro L, De Benedittis C, Martelli M, Iurlo A, Orofino N, Sica S, Sorà F, Lunghi F, Ciceri F, Galimberti S, Baratè C, Bonifacio M, Scaffidi L, Castagnetti F, Gugliotta G, Albano F, Russo Rossi AV, Stagno F, di Raimondo F, D'Adda M, di Bona E, Abruzzese E, Binotto G, Sancetta R, Salvucci M, Capodanno I, Girasoli M, Coluzzi S, Attolico I, Musolino C, Calistri E, Annunziata M, Bocchia M, Stella S, Serra A, Errichiello S, Saglio G, Pane F, Vigneri P, Mignone F, Laginestra MA, Pileri SA, Percesepe A, Tenti E, Rosti G, Baccarani M, Cavo M, and Martinelli G
- Subjects
- Adult, Aged, Aged, 80 and over, Drug Resistance, Neoplasm, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Mutation Rate, Prospective Studies, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Protein Kinase Inhibitors therapeutic use
- Abstract
In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms., (© 2020 by The American Society of Hematology.)
- Published
- 2020
- Full Text
- View/download PDF
4. Recurrent arterial occlusive events in patients with chronic myeloid leukemia treated with second- and third-generation tyrosine kinase inhibitors and role of secondary prevention.
- Author
-
Caocci G, Mulas O, Bonifacio M, Abruzzese E, Galimberti S, Orlandi EM, Iurlo A, Annunziata M, Luciano L, Castagnetti F, Gozzini A, Stagno F, Binotto G, Pregno P, Albano F, Martino B, Fozza C, Scaffidi L, Trawinska MM, Baratè C, Elena C, Cattaneo D, Scalzulli E, La Nasa G, Foà R, and Breccia M
- Subjects
- Aged, Aged, 80 and over, Arterial Occlusive Diseases epidemiology, Arterial Occlusive Diseases prevention & control, Female, Follow-Up Studies, Humans, Incidence, Italy epidemiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Middle Aged, Recurrence, Risk Factors, Time Factors, Treatment Outcome, Anticoagulants therapeutic use, Arterial Occlusive Diseases etiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Platelet Aggregation Inhibitors therapeutic use, Protein Kinase Inhibitors therapeutic use, Secondary Prevention methods
- Abstract
Background: Risk of death is particularly high in patients with a previous history of arterial occlusive events (AOEs) and the probability for a recurrent event is around 20%. Little is known about recurrent AOE and the role of secondary prevention in patients with Chronic Myeloid Leukemia (CML) with previous AOE, treated with second- and third-generation tyrosine kinase inhibitors (2
ndG /3rdG TKIs), nilotinib, dasatinib, bosutinib and ponatinib., Methods: We identified a real-life cohort of 57 consecutive adult CML patients treated with 2ndG /3rdG TKI. All patients had a previous history of AOE. Ongoing use of secondary prevention of AOE (including antiplatelet agents, anticoagulant therapy, and statins) before starting a 2ndG /3rdG TKI was recorded, as well as CV risk factors., Results: The 60-month cumulative incidence rate of recurrent AOEs was 47.8 ± 10.9%. Despite a history of AOE, 10 patients (16%) were not receiving secondary preventative measures. Patients treated with nilotinib and ponatinib showed a higher incidence of recurrent AOEs (76.7 ± 14.3% and 64 ± 20.1%, respectively) than those treated with dasatinib and bosutinib (44 ± 24.2% and 30.5 ± 15.5%, respectively) (p = 0.01). Only treatment with a 2ndG /3rdG TKI given as second or subsequent line therapy showed a significant association with an increased incidence of recurrent AOE (p = 0.039). Overall, 17 recurrent AOEs were observed; 3 CV-related deaths were reported., Conclusion: CML patients with a previous history of AOE treated with 2ndG /3rdG TKI represent a particular patient population with a higher probability of experiencing a recurrent AOE; individualized treatment is needed to optimize secondary prevention., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
5. Digital PCR improves the quantitation of DMR and the selection of CML candidates to TKIs discontinuation.
- Author
-
Bernardi S, Malagola M, Zanaglio C, Polverelli N, Dereli Eke E, D'Adda M, Farina M, Bucelli C, Scaffidi L, Toffoletti E, Deambrogi C, Stagno F, Bergamaschi M, Franceschini L, Abruzzese E, Divona MD, Gobbi M, Di Raimondo F, Gaidano G, Tiribelli M, Bonifacio M, Cattaneo C, Iurlo A, and Russo D
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Gene Expression Regulation, Neoplastic, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Male, Middle Aged, Neoplasm, Residual genetics, Sensitivity and Specificity, Treatment Outcome, Young Adult, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Neoplasm, Residual diagnosis, Polymerase Chain Reaction methods, Protein Kinase Inhibitors therapeutic use
- Abstract
Treatment-free remission (TFR) by tyrosine kinase inhibitors (TKI) discontinuation in patients with deep molecular response (DMR) is a paramount goal in the current chronic myeloid leukemia (CML) therapeutic strategy. The best DMR level by real-time quantitative PCR (RT-qPCR) for TKI discontinuation is still a matter of debate. To compare the accuracy of digital PCR (dPCR) and RT-qPCR for BCR-ABL1 transcript levels detection, 142 CML patients were monitored for a median time of 24 months. Digital PCR detected BCR-ABL1 transcripts in the RT-qPCR undetectable cases. The dPCR analysis of the samples, grouped by the MR classes, revealed a significant difference between MR
4.0 and MR4.5 (P = 0.0104) or MR5.0 (P = 0.0032). The clinical and hematological characteristics of the patients grouped according to DMR classes (MR4.0 vs MR4.5-5.0 ) were superimposable. Conversely, patients with dPCR values <0.468 BCR-ABL1 copies/µL (as we previously described) showed a longer DMR duration (P = 0.0220) and mainly belonged to MR4.5-5.0 (P = 0.0442) classes compared to patients with higher dPCR values. Among the 142 patients, 111 (78%) discontinued the TKI treatment; among the 111 patients, 24 (22%) lost the MR3.0 or MR4.0 . RT-qPCR was not able to discriminate patients with higher risk of MR loss after discontinuation (P = 0.8100). On the contrary, according to dPCR, 12/25 (48%) patients with BCR-ABL1 values ≥0.468 and 12/86 (14%) patients with BCR-ABL1 values <0.468 lost DMR in this cohort, respectively (P = 0.0003). Treatment-free remission of patients who discontinued TKI with a dPCR <0.468 was significantly higher compared to patients with dPCR ≥ 0.468 (TFR at 2 years 83% vs 52% P = 0.0017, respectively). In conclusion, dPCR resulted in an improved recognition of stable DMR and of candidates to TKI discontinuation., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)- Published
- 2019
- Full Text
- View/download PDF
6. Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice: Identification of risk factors and the role of prophylaxis.
- Author
-
Caocci G, Mulas O, Annunziata M, Luciano L, Bonifacio M, Orlandi EM, Pregno P, Galimberti S, Russo Rossi A, Abruzzese E, Iurlo A, Martino B, Sgherza N, Binotto G, Castagnetti F, Gozzini A, Fozza C, Bocchia M, Sicuranza A, Stagno F, Efficace F, Usala E, De Gregorio F, Scaffidi L, Elena C, Pirillo F, Baratè C, Trawinska MM, Cattaneo D, Labate C, Gugliotta G, Molica M, Specchia G, La Nasa G, Foà R, and Breccia M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cardiotoxicity etiology, Female, Humans, Italy, Male, Middle Aged, Protein Kinase Inhibitors therapeutic use, Protein-Tyrosine Kinases antagonists & inhibitors, Risk Assessment, Risk Factors, Young Adult, Cardiotoxicity prevention & control, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Protein Kinase Inhibitors toxicity
- Published
- 2018
- Full Text
- View/download PDF
7. Imatinib-treated chronic myeloid leukemia patients with discordant response between cytogenetic and molecular tests at 3 and 6 month time-points have a reduced probability of subsequent optimal response.
- Author
-
Bonifacio M, Binotto G, Maino E, Calistri E, Marin L, Scaffidi L, Frison L, De Marchi F, Krampera M, Semenzato G, Fanin R, Ambrosetti A, and Tiribelli M
- Subjects
- Chromosome Aberrations, Fusion Proteins, bcr-abl genetics, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Retrospective Studies, Time Factors, Treatment Outcome, Antineoplastic Agents therapeutic use, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Protein Kinase Inhibitors therapeutic use
- Published
- 2015
- Full Text
- View/download PDF
8. Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: The NEXT-in-CML study
- Author
-
Anna Serra, Antonio Percesepe, Gabriele Gugliotta, Caterina Musolino, Gianni Binotto, Elisabetta Abruzzese, Immacolata Attolico, Gianantonio Rosti, Mario Annunziata, Rosaria Sancetta, Mariella Girasoli, Fabrizio Pane, Maria Antonella Laginestra, Sara Galimberti, Alessandra Iurlo, Stefania Stella, Sabrina Coluzzi, Simona Sica, Monica Bocchia, Marzia Salvucci, Francesca Lunghi, Fabio Stagno, Nicola Orofino, Stefano Pileri, Federica Sorà, Santa Errichiello, Elisabetta Calistri, Paolo Vigneri, Fausto Castagnetti, Michele Baccarani, Luana Bavaro, Michele Cavo, Eros Di Bona, Francesco Di Raimondo, Claudia Baratè, Margherita Martelli, Simona Soverini, Antonella Russo Rossi, Francesco Albano, Mariella D'Adda, Fabio Ciceri, Flavio Mignone, Elena Tenti, Caterina De Benedittis, Giuseppe Saglio, Isabella Capodanno, Giovanni Martinelli, Massimiliano Bonifacio, Luigi Scaffidi, Soverini, S., Bavaro, L., de Benedittis, C., Martelli, M., Iurlo, A., Orofino, N., Sica, S., Sora, F., Lunghi, F., Ciceri, F., Galimberti, S., Barate, C., Bonifacio, M., Scaffidi, L., Castagnetti, F., Gugliotta, G., Albano, F., Rossi, A. V. R., Stagno, F., di Raimondo, F., D'Adda, M., di Bona, E., Abruzzese, E., Binotto, G., Sancetta, R., Salvucci, M., Capodanno, I., Girasoli, M., Coluzzi, S., Attolico, I., Musolino, C., Calistri, E., Annunziata, M., Bocchia, M., Stella, S., Serra, A., Errichiello, S., Saglio, G., Pane, F., Vigneri, P., Mignone, F., Laginestra, M. A., Pileri, S. A., Percesepe, A., Tenti, E., Rosti, G., Baccarani, M., Cavo, M., Martinelli, G., Soverini, Simona, Bavaro, Luana, De Benedittis, Caterina, Martelli, Margherita, Iurlo, Alessandra, Orofino, Nicola, Sica, Simona, Sora, Federica, Lunghi, Francesca, Ciceri, Fabio, Galimberti, Sara, Baratè, Claudia, Bonifacio, Massimiliano, Scaffidi, Luigi, Castagnetti, Fausto, Gugliotta, Gabriele, Albano, Francesco, Russo Rossi, Antonella Vita, Stagno, Fabio, Di Raimondo, Francesco, D'Adda, Mariella, Di Bona, Ero, Abruzzese, Elisabetta, Binotto, Gianni, Sancetta, Rosaria, Salvucci, Marzia, Capodanno, Isabella, Girasoli, Mariella, Coluzzi, Sabrina, Attolico, Immacolata, Musolino, Caterina, Calistri, Elisabetta, Annunziata, Mario, Bocchia, Monica, Stella, Stefania, Serra, Anna, Errichiello, Santa, Saglio, Giuseppe, Pane, Fabrizio, Vigneri, Paolo G, Mignone, Flavio, Laginestra, Maria Antonella, Pileri, Stefano A, Percesepe, Antonio, Tenti, Elena, Rosti, Gianantonio, Baccarani, Michele, Cavo, Michele, and Martinelli, Giovanni
- Subjects
Oncology ,Male ,Mutation rate ,bcr-abl ,Drug Resistance ,Fusion Proteins, bcr-abl ,Gene mutation ,medicine.disease_cause ,Settore MED/01 - STATISTICA MEDICA ,Biochemistry ,Adult ,Aged ,Aged, 80 and over ,Drug Resistance, Neoplasm ,Female ,High-Throughput Nucleotide Sequencing ,Humans ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Middle Aged ,Mutation ,Mutation Rate ,Prospective Studies ,Protein Kinase Inhibitors ,hemic and lymphatic diseases ,80 and over ,cml mutation ,BCR-ABL mutations ,Chronic ,Prospective cohort study ,Sanger sequencing ,Leukemia ,Chronic myeloid leukemia ,Myeloid leukemia ,Hematology ,TKI ,NGS ,symbols ,Human ,medicine.medical_specialty ,Immunology ,symbols.namesake ,CML, TKIs, BCR-ABL1 ,Chronic myeloid leukemia,TKI,BCR-ABL mutations,Sanger Sequencing,NGS ,Internal medicine ,medicine ,business.industry ,Fusion Proteins ,Cell Biology ,medicine.disease ,Clinical trial ,Prospective Studie ,Sanger Sequencing ,Neoplasm ,BCR-ABL Positive ,business ,Myelogenous - Abstract
In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.
- Published
- 2020
9. Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice: Identification of risk factors and the role of prophylaxis
- Author
-
Bruno Martino, Robin Foà, Massimo Breccia, Daniele Cattaneo, Francesca Pirillo, Antonella Gozzini, Nicola Sgherza, Alessandra Iurlo, Luigi Scaffidi, Monica Bocchia, Fabio Stagno, Claudio Fozza, Patrizia Pregno, Antonella Russo Rossi, Fabio Efficace, Gabriele Gugliotta, Sara Galimberti, Fausto Castagnetti, Luigiana Luciano, Giorgina Specchia, Massimiliano Bonifacio, Malgorzata Monika Trawinska, Elisabetta Abruzzese, Mario Annunziata, Giovanni Caocci, Ester Orlandi, Chiara Elena, Fiorenza De Gregorio, Anna Sicuranza, Emilio Usala, Claudia Baratè, Matteo Molica, Claudia Labate, Giorgio La Nasa, Gianni Binotto, Olga Mulas, Caocci, Giovanni, Mulas, Olga, Annunziata, Mario, Luciano, Luigiana, Bonifacio, Massimiliano, Orlandi, Ester Maria, Pregno, Patrizia, Galimberti, Sara, Russo Rossi, Antonella, Abruzzese, Elisabetta, Iurlo, Alessandra, Martino, Bruno, Sgherza, Nicola, Binotto, Gianni, Castagnetti, Fausto, Gozzini, Antonella, Fozza, Claudio, Bocchia, Monica, Sicuranza, Anna, Stagno, Fabio, Efficace, Fabio, Usala, Emilio, De Gregorio, Fiorenza, Scaffidi, Luigi, Elena, Chiara, Pirillo, Francesca, Baratè, Claudia, Trawinska, Malgorzata Monika, Cattaneo, Daniele, Labate, Claudia, Gugliotta, Gabriele, Molica, Matteo, Specchia, Giorgina, La Nasa, Giorgio, Foà, Robin, and Breccia, Massimo
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,030204 cardiovascular system & hematology ,Risk Assessment ,03 medical and health sciences ,Myelogenous ,Young Adult ,0302 clinical medicine ,Risk Factors ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,80 and over ,Humans ,Young adult ,Chronic ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Cardiotoxicity ,Hematology ,Leukemia ,business.industry ,Myeloid leukemia ,Middle Aged ,Protein-Tyrosine Kinases ,medicine.disease ,Italy ,030220 oncology & carcinogenesis ,Female ,BCR-ABL Positive ,Risk assessment ,business ,Tyrosine kinase - Abstract
NA
- Published
- 2018
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.