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3. 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

Chiara Elena, Alessandra Iurlo, Antonella Gozzini, Giorgio La Nasa, Claudia Baratè, Gabriele Gugliotta, Bruno Martino, Francesca Pirillo, Fiorenza De Gregorio, Fabio Efficace, Monica Bocchia, Massimo Breccia, Claudio Fozza, Elisabetta Abruzzese, Mario Annunziata, Sara Galimberti, Gianni Binotto, Fabio Stagno, Isabella Capodanno, Malgorzata Monika Trawinska, Anna Sicuranza, Maria Pina Simula, Robin Foà, Debora Luzi, Patrizia Pregno, Rossella Stella, Imma Attolico, Luigiana Luciano, Francesco Albano, Giovanni Caocci, Ester Orlandi, Daniele Cattaneo, Olga Mulas, Nicola Sgherza, Luigi Scaffidi, Massimiliano Bonifacio, Emilia Scalzulli, Mario Tiribelli, Fausto Castagnetti, Mulas O., Caocci G., Stagno F., Bonifacio M., Annunziata M., Luciano L., Orlandi E.M., 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 M.P., Scaffidi L., De Gregorio F., Elena C., Trawinska M.M., Cattaneo D., Attolico I., Barate C., Pirillo F., Sicuranza A., Gugliotta G., Stella R., Scalzulli E., Iurlo A., Foa R., Breccia M., and La Nasa G.

Subjects
Male, Myeloid, Angiotensin-Converting Enzyme Inhibitors, Gastroenterology, Cohort Studies, Renin-Angiotensin System, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, 80 and over, Cumulative incidence, Chronic, Aged, 80 and over, Leukemia, Arterial occlusive events, Incidence, Ponatinib, Angiotensin Receptor Antagonist, Chronic myeloid leukemia, Myeloid leukemia, Hematology, General Medicine, Middle Aged, TKI, Dasatinib, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Combination, Hypertension, Drug Therapy, Combination, Female, Survival Analysi, medicine.drug, Human, Renin angiotensin system inhibitors, Adult, medicine.medical_specialty, Arterial occlusive event, Protein Kinase Inhibitor, 03 medical and health sciences, Angiotensin Receptor Antagonists, Drug Therapy, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Artery occlusion, Protein Kinase Inhibitors, Aged, business.industry, Risk Factor, Angiotensin-Converting Enzyme Inhibitor, Thrombosis, Renin angiotensin system inhibitor, Survival Analysis, Blood pressure, chemistry, Nilotinib, BCR-ABL Positive, Cohort Studie, business, 030215 immunology, Myelogenous
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 3rdG TKIs.

Published
2020

4. Favorable outcome of chronic myeloid leukemia co-expressing e13a2 and e14a2 transcripts, treated with nilotinib

Author

Sara Galimberti, Giovanni Caocci, Ester Orlandi, Mario Annunziata, Gabriele Gugliotta, Emilia Scalzulli, Alessandra Iurlo, Chiara Elena, Elisabetta Abruzzese, Daniele Cattaneo, Bruno Martino, Malgorzata Monika Trawinska, Giorgio La Nasa, Luigi Scaffidi, Francesca Pirillo, Anna Sicuranza, Luigiana Luciano, Fausto Castagnetti, Patrizia Pregno, Monica Bocchia, Nicola Sgherza, Francesco Albano, Robin Foà, Massimo Breccia, Fiorenza De Gregorio, Antonella Gozzini, Massimiliano Bonifacio, Claudia Baratè, Imma Attolico, Maria Pina Simula, Gianni Binotto, Claudio Fozza, Olga Mulas, Mulas O., Caocci G., Annunziata M., Martino B., Luciano L., Castagnetti F., Pregno P., Galimberti S., Albano F., Orlandi E.M., Sgherza N., Iurlo A., Bonifacio M., Binotto G., Gozzini A., Bocchia M., Abruzzese E., Fozza C., Simula M.P., De Gregorio F., Gugliotta G., Pirillo F., Barate C., Attolico I., Elena C., Cattaneo D., Scaffidi L., Sicuranza A., Trawinska M.M., Scalzulli E., Foa R., Breccia M., and La Nasa G.

Subjects
Oncology, Male, Cancer Research, Chromosomes, Human, Pair 22, bcr-abl, Messenger, Fusion Proteins, bcr-abl, Translocation, Genetic, 80 and over, Favorable outcome, RNA, Neoplasm, Chronic, Aged, 80 and over, Leukemia, Follow up studies, Myeloid leukemia, molecular response, Hematology, General Medicine, Middle Aged, Survival Rate, outcome, Female, Chromosomes, Human, Pair 9, medicine.drug, Human, Pair 9, Adult, medicine.medical_specialty, Disease free survival, transcript type, MEDLINE, Translocation, Disease-Free Survival, Chromosomes, Follow-Up Studie, Text mining, Genetic, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, RNA, Messenger, Survival rate, nilotinib, Aged, Follow-Up Studies, Pyrimidines, business.industry, chronic myeloid leukemia, nilotinib, transcript type, molecular response, outcome, Fusion Proteins, Nilotinib, Pyrimidine, RNA, Neoplasm, BCR-ABL Positive, Pair 22, business, Myelogenous
Abstract

No abstract available.

Published
2020

5. Low low-density lipoprotein (LDL), cholesterol and triglycerides plasma levels are associated with reduced risk of arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life. A Campus CML study

Author

Emilia Scalzulli, Fabio Efficace, Giovanni Caocci, Ester Orlandi, Sara Galimberti, Mario Tiribelli, Daniele Cattaneo, Elisabetta Abruzzese, Luigi Scaffidi, Olga Mulas, Immacolata Attolico, Debora Luzi, Massimiliano Bonifacio, Robin Foà, Chiara Elena, Rossella Stella, Fausto Castagnetti, Massimo Breccia, Maria Pina Simula, Claudia Baratè, Luigiana Luciano, Malgorzata Monika Trawinska, Francesco Albano, Fabio Stagno, Patrizia Pregno, Antonella Gozzini, Gianni Binotto, Gabriele Gugliotta, Giorgio La Nasa, Francesca Pirillo, Nicola Sgherza, Mario Annunziata, Alessandra Iurlo, Claudio Fozza, Isabella Capodanno, Fiorenza De Gregorio, Caocci G., Mulas O., Capodanno I., Abruzzese E., Iurlo A., Luciano L., Albano F., Annunziata M., Tiribelli M., Bonifacio M., Galimberti S., Castagnetti F., Sgherza N., Stagno F., Gozzini A., Orlandi E.M., Luzi D., Binotto G., Pregno P., Fozza C., Efficace F., Simula M.P., Trawinska M.M., Cattaneo D., De Gregorio F., Attolico I., Stella R., Scaffidi L., Barate C., Gugliotta G., Scalzulli E., Elena C., Pirillo F., Foa R., Breccia M., and Nasa G.L.

Subjects
Adult, Male, medicine.medical_specialty, Antineoplastic Agents, Arterial Occlusive Diseases, Gastroenterology, lcsh:RC254-282, chronic myeloid leukemia, TKI, ponatinib, arterial occlusive events, Article, chemistry.chemical_compound, Young Adult, Myeloproliferative disease, High-density lipoprotein, Low low-density lipoprotein, LDL, cholesterol, triglycerides, arterial occlusive events, chronic myeloid leukemia, ponatinib, CML, Campus, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Medicine, Humans, ponatinib, Artery occlusion, arterial occlusive events, Triglycerides, Aged, Aged, 80 and over, business.industry, Cholesterol, Ponatinib, Imidazoles, Myeloid leukemia, Hematology, Middle Aged, Protective Factors, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, TKI, Lipoproteins, LDL, Pyridazines, Leukemia, Oncology, chemistry, Risk factors, Low-density lipoprotein, Female, business, Dyslipidemia
Abstract

Not available.

Published
2020

6. Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second- and third-generation tyrosine kinase inhibitors

Author

Gabriele Gugliotta, Francesca Pirillo, Bruno Martino, Fausto Castagnetti, Chiara Elena, Antonella Gozzini, Giorgio La Nasa, Massimiliano Bonifacio, Claudia Baratè, Gianni Binotto, Robin Foà, Daniele Cattaneo, Nicola Sgherza, Alessandra Iurlo, Monica Bocchia, Elisabetta Abruzzese, Mario Annunziata, Claudio Fozza, Fiorenza De Gregorio, Matteo Molica, Luigi Scaffidi, Sara Galimberti, Olga Mulas, Giovanni Caocci, Imma Attolico, Ester Orlandi, Maria Pina Simula, Luigiana Luciano, Massimo Breccia, Francesco Albano, Fabio Stagno, Patrizia Pregno, Anna Sicuranza, Malgorzata Monika Trawinska, Caocci G., Mulas O., Annunziata M., Luciano L., Abruzzese E., Bonifacio M., Orlandi E.M., Albano F., Galimberti S., Iurlo A., Pregno P., Sgherza N., Martino B., Binotto G., Castagnetti F., Gozzini A., Bocchia M., Fozza C., Stagno F., Simula M.P., De Gregorio F., Trawinska M.M., Scaffidi L., Elena C., Attolico I., Barate C., Cattaneo D., Pirillo F., Gugliotta G., Sicuranza A., Molica M., La Nasa G., Foa R., and Breccia M.

Subjects
Male, Chronic myeloid leuk, Dasatinib, emia, Long Term Adverse Effects, Long Term Adverse Effect, 030204 cardiovascular system & hematology, Antineoplastic Agent, chemistry.chemical_compound, 0302 clinical medicine, Cardiovascular Disease, Cardiovascular toxicity, Ischemic heart disease, TKI, Aged, Antineoplastic Agents, Female, Humans, Italy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Life Expectancy, Mortality, Protein Kinase Inhibitors, Risk Adjustment, Aniline Compounds, Cardiotoxicity, Cardiovascular Diseases, Imidazoles, Nitriles, Pyridazines, Pyrimidines, Quinolines, 030212 general & internal medicine, Chronic, education.field_of_study, Leukemia, Mortality rate, Ponatinib, Aniline Compound, a, Pyridazine, Cardiology and Cardiovascular Medicine, Nitrile, Bosutinib, Human, medicine.drug, medicine.medical_specialty, Population, Protein Kinase Inhibitor, 03 medical and health sciences, Internal medicine, medicine, education, Imidazole, Survival rate, business.industry, Standardized mortality ratio, Pyrimidine, Nilotinib, chemistry, BCR-ABL Positive, business, Myelogenous
Abstract

Background Limited information is available regarding the rate of long-term cardiovascular (CV) mortality in chronic myeloid leukaemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (2ndG/3rdG TKIs) in the real-life practice. Methods We identified 656 consecutive CML patients treated with nilotinib, dasatinib, bosutinib and ponatinib. Results The 15-year CV-mortality free survival was 93 ± 2.8%. Age ≥65 years (p = 0.005) and a positive history of CV disease (p = 0.04) were significantly associated with a lower CV-mortality free survival. CV disease accounted for 16.5% and 5% of potential years of life lost (PYLL) in male and female patients, respectively. The standard mortality ratio (SMR) following ischemic heart disease (IHD) was 3.9 in males and 3.8 in female patients, meaning an excess of IHD deaths observed, in comparison with the population of control. Conclusion. Prevention strategies based on CV risk factors, in particular in those patients with a previous history of CV disease, should be considered.

Published
2019

7. 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

Claudio Fozza, Giovanni Caocci, Ester Orlandi, Massimiliano Bonifacio, Chiara Elena, Bruno Martino, Daniele Cattaneo, Mario Annunziata, Luigi Scaffidi, Antonella Gozzini, Sara Galimberti, Olga Mulas, Fabio Stagno, Gianni Binotto, Patrizia Pregno, Giorgio La Nasa, Robin Foà, Fausto Castagnetti, Alessandra Iurlo, Malgorzata Monika Trawinska, Massimo Breccia, Emilia Scalzulli, Luigiana Luciano, Francesco Albano, Claudia Baratè, Elisabetta Abruzzese, Caocci G., Mulas O., Bonifacio M., Abruzzese E., Galimberti S., Orlandi E.M., 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 M.M., Barate C., Elena C., Cattaneo D., Scalzulli E., La Nasa G., Foa R., and Breccia M.

Subjects
Oncology, Male, Time Factors, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, Recurrent arterial occlusive event, Recurrence, Risk Factors, 80 and over, Secondary Prevention, Medicine, Cumulative incidence, 030212 general & internal medicine, Chronic, Aged, 80 and over, Chronic myeloid leukemia, Secondary prophylaxis, Leukemia, Incidence (epidemiology), Incidence, Ponatinib, Myeloid leukemia, Middle Aged, Aged, Anticoagulants, Arterial Occlusive Diseases, Female, Follow-Up Studies, Humans, Italy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Platelet Aggregation Inhibitors, Protein Kinase Inhibitors, Treatment Outcome, Dasatinib, Platelet aggregation inhibitor, Cardiology and Cardiovascular Medicine, Bosutinib, medicine.drug, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, business.industry, chemistry, Nilotinib, BCR-ABL Positive, business, Myelogenous
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 (2ndG/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.

Published
2019

8. Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart

Author

Giovanni Caocci, Massimo Breccia, Ester Orlandi, Antonella Gozzini, Robin Foà, Luigiana Luciano, Nicola Sgherza, Francesco Albano, Sara Galimberti, Massimiliano Bonifacio, Elisabetta Abruzzese, Gabriele Gugliotta, Olga Mulas, Daniele Cattaneo, Gianni Binotto, Chiara Elena, Luigi Scaffidi, Claudia Baratè, Fabio Stagno, Patrizia Pregno, Immacolata Attolico, Fiorenza De Gregorio, Emilia Scalzulli, Fausto Castagnetti, Mario Annunziata, Giorgio La Nasa, Alessandra Iurlo, Francesca Pirillo, Malgorzata Monika Trawinska, Claudio Fozza, Caocci G., Mulas O., Abruzzese E., Luciano L., Iurlo A., Attolico I., Castagnetti F., Galimberti S., Sgherza N., Bonifacio M., Annunziata M., Gozzini A., Orlandi E.M., Stagno F., Binotto G., Pregno P., Fozza C., Trawinska M.M., De Gregorio F., Cattaneo D., Albano F., Gugliotta G., Barate C., Scaffidi L., Elena C., Pirillo F., Scalzulli E., La Nasa G., Foa R., and Breccia M.

Subjects
Male, Cancer Research, Decision Support Systems, Medical Oncology, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Retrospective Studie, Original Research Articles, Epidemiology, 80 and over, Medicine, Cumulative incidence, ponatinib, Original Research Article, arterial occlusive event, Chronic, Aged, 80 and over, Aspirin, Leukemia, Incidence (epidemiology), Incidence, Ponatinib, Imidazoles, Hematology, General Medicine, Middle Aged, Pyridazines, Treatment Outcome, Oncology, Italy, 030220 oncology & carcinogenesis, Hypertension, Female, prophylaxis, Pyridazine, medicine.drug, Human, Adult, medicine.medical_specialty, Chronic myeloid leukemia, Cardiology, 03 medical and health sciences, Clinical, Young Adult, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Risk factor, Imidazole, Retrospective Studies, Aged, business.industry, prophylaxi, Risk Factor, Coronary Occlusion, Decision Support Systems, Clinical, Retrospective cohort study, Blood pressure, chemistry, BCR-ABL Positive, business, 030215 immunology, Myelogenous
Abstract

Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 60-month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28months (range, 3-69months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P&nbsp

Published
2019

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