32 results on '"Maria Pina Simula"'
Search Results
2. Treatment-free remission in chronic myeloid leukemia patients treated front-line with nilotinib: 10-year followup of the GIMEMA CML 0307 study
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Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Luciano Levato, Tamara Intermesoli, Mariella D'Adda, Marzia Salvucci, Fabio Stagno, Giovanna Rege-Cambrin, Mario Tiribelli, Bruno Martino, Monica Bocchia, Michele Cedrone, Elena Trabacchi, Francesco Cavazzini, Ferdinando Porretto, Federica Sorà, Maria Pina Simula, Francesco Albano, Simona Soverini, Robin Foà, Fabrizio Pane, Michele Cavo, Giuseppe Saglio, Michele Baccarani, and Gianantonio Rosti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
We report the final analysis, with a 10-year follow-up, of the phase II study GIMEMA CML 0307 (NCT 00481052), which enrolled 73 adult patients (median age 51 years; range, 18-83) with newly diagnosed chronic-phase chronic myeloid leukemia to investigate the efficacy and the toxicity of front-line treatment with nilotinib. The initial dose was 400 mg twice daily; the dose was reduced to 300 mg twice daily as soon as this dose was approved and registered. The 10-year overall survival and progression- free survival were 94.5%. At the last contact, 36 (49.3%) patients were continuing nilotinib (22 patients at 300 mg twice daily, 14 at lower doses), 18 (24.7%) patients were in treatment-free remission, 14 (19.2%) were receiving other tyrosinekinase inhibitors and four (5.5%) patients have died. The rates of major and deep molecular responses by 10 years were 96% and 83%, respectively. The median times to major and deep molecular response were 6 and 18 months, respectively. After a median duration of nilotinib treatment of 88 months, 24 (32.9%) patients discontinued nilotinib while in stable deep molecular response. In these patients, the 2-year estimated treatment-free survival was 72.6%. The overall treatment-free remission rate, calculated on all enrolled patients, was 24.7% (18/73 patients). Seventeen patients (23.3%), at a median age of 69 years, had at least one arterial obstructive event. In conclusion, the use of nilotinib front-line in chronic phase chronic myeloid leukemia can induce a stable treatment-free remission in a relevant number of patients, although cardiovascular toxicity remains of concern.
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- 2022
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3. Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
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Giovanni Caocci, Martino Deidda, Antonio Noto, Marianna Greco, Maria Pina Simula, Olga Mulas, Daniele Cocco, Claudia Fattuoni, Giuseppe Mercuro, Giorgio La Nasa, and Christian Cadeddu Dessalvi
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Chronic myeloid leukemia ,cardiovascular adverse events ,tyrosine kinase inhibitors ,GC-MS metabolomics ,Medicine - Abstract
Background: Cardiovascular adverse events (CV-AEs) are considered critical complications in chronic myeloid leukemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (TKIs). The aim of our study was to assess the correlation between metabolic profiles and CV-AEs in CML patients treated with TKIs. Methods: We investigated 39 adult CML patients in chronic-phase (mean age 49 years, range 24–70 years), with no comorbidities evidenced at baseline, who were consecutively identified with CML and treated with imatinib, nilotinib, dasatinib, and ponatinib. All patients performed Gas-Chromatography-Mass-Spectrometry-based metabolomic analysis and were divided into two groups (with and without CV-AEs). Results: Ten CV-AEs were documented. Seven CV-AEs were rated as 3 according to the Common Toxicity Criteria, and one patient died of a dissecting aneurysm of the aorta. The patients’ samples were clearly separated into two groups after analysis and the main discriminant metabolites were tyrosine, lysine, glutamic acid, ornithine, 2-piperdinecarboxylic acid, citric acid, proline, phenylalanine, threonine, mannitol, leucine, serine, creatine, alanine, and 4-hydroxyproline, which were more abundant in the CV-AE group. Conversely, myristic acid, oxalic acid, arabitol, 4-deoxy rithronic acid, ribose, and elaidic acid were less represented in the CV-AE group. Conclusions: CML patients with CV-AEs show a different metabolic profile, suggesting probable mechanisms of endothelial damage.
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- 2020
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4. CD4+ and CD8+ T-Cell Skewness in Classic Kaposi Sarcoma
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Antonio Galleu, Claudio Fozza, Maria Pina Simula, Salvatore Contini, Patrizia Virdis, Giovanna Corda, Simonetta Pardini, Francesca Cottoni, Sara Pruneddu, Antonio Angeloni, Simona Ceccarelli, and Maurizio Longinotti
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
It is widely accepted that a deranged immune system plays a key role in the onset and evolution of classic Kaposi sarcoma (CKS). Nevertheless, the usage of the T-cell receptor (TCR) β-variable (BV) chain repertoire expressed by peripheral blood lymphocytes in patients with CKS is still unknown. With the aim of providing some further insights into the complex role of the immune system in CKS pathogenesis, we performed an extensive analysis of the TCR BV repertoire in both CD4+ and CD8+ T cells in 30 human herpesvirus 8-positive Sardinian patients with CKS and an equal number of age-matched healthy controls. We used a panel of monoclonal antibodies covering approximately 70% of human BV subfamilies and third complementarity determining region (CDR3) spectratyping. Patients with CKS showed an increased frequency of BV expansions in both CD4+ and CD8+ lymphocytes, with no prevalent clones. On spectratyping analysis, most of the 720 BV CDR3 profiles obtained from both CD4+ and CD8+ T cells in patients with CKS were skewed. In particular, the surprising increase of BV skewing observed in CD4+ lymphocytes mimics the pattern of progressive TCR BV narrowing described in responses to persistent viral antigen stimulations. Our findings support the hypothesis that CKS evolution is associated with inadequate activation rather than impairment of the immune system.
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- 2012
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5. Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors
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Francesco Boi, Fabiana Pani, Maria Pina Simula, Stefano Mariotti, Giovanni Caocci, Fernanda Velluzzi, G La Nasa, Andrea Loviselli, Olga Mulas, and R Rodia
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Male ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Thyroid Gland ,Long Term Adverse Effects ,030209 endocrinology & metabolism ,Thyroid Function Tests ,medicine.disease_cause ,Molecular response ,Gastroenterology ,Thyroiditis ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Hypothyroidism ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,Humans ,Thyroid abnormalities ,Euthyroid ,Protein Kinase Inhibitors ,Thyroid autoimmunity ,Autoantibodies ,Ultrasonography ,Tyrosine kinase inhibitors ,business.industry ,Chronic myeloid leukemia ,Thyroid ,Thyroiditis, Autoimmune ,Myeloid leukemia ,Middle Aged ,Prognosis ,medicine.disease ,Anti-thyroid autoantibodies ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Original Article ,Female ,Drug Monitoring ,Thyroid function ,business ,Tyrosine kinase - Abstract
Purpose Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors. Methods We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response. Results Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto’s thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto’s thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto’s thyroiditis patients with major molecular response. Conclusions Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.
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- 2021
6. Thromboembolic Complications PICC-Related in Adult Patients Affected By Hematologic Diseases: A 13-Years Monocentric Experience
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Daniele Derudas, Stefania Massidda, Maria Pina Simula, Daniela Dessì, Sara Veronica Usai, Claudio Romani, Giuseppe Longhitano, Daniela Ibba, Loredana Aracu, and Giorgio La Nasa
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
7. PICC Insertion and Management in Hodgkin and NON-Hodgkin Lymphomas: A 13-YEARS Monocentric Experience
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Daniele Derudas, Maria Pina Simula, Stefania Massidda, Daniela Dessì, Sara Veronica Usai, Giuseppe Longhitano, Daniela Ibba, Loredana Aracu, and Giorgio La Nasa
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
8. Mimicking Multiple Myeloma: the importance of the differential diagnosis
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Daniele Derudas, Concu Claudia, Tania Durzu, Doloretta Piras, Sonia Nemolato, Annamaria Liguori, Maria Pina Simula, and Giorgio La Nasa
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Here we describe the case of a caucasian man referred to our Center for a suspicion of Multiple Myeloma which comprehensive work-up ruled out the presence of plasma cells neoplasm and allowed us to perform a diagnosis of brown tumor (BT).
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- 2022
9. Health-related quality of life profile of patients with immune thrombocytopenia in the real life is impaired by splenectomy
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Giovanni, Caocci, Fabio, Efficace, Olga, Mulas, Francesco, Cottone, Alessia, Maxia, Alessandro, Costa, Maria Pina, Simula, Emilio, Usala, and Giorgio, La Nasa
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Purpura, Thrombocytopenic, Idiopathic ,Thrombopoietin ,Recombinant Fusion Proteins ,Quality of Life ,Splenectomy ,Humans ,Receptors, Fc ,Receptors, Thrombopoietin - Abstract
The impact of splenectomy on health-related quality of life (HRQoL) in patients with immune thrombocytopenia (ITP) remains scarcely explored. Therefore, we evaluated HRQoL with the 36-Item Short-Form Health Survey (SF-36) in an internal cohort of 69 chronic ITP patients, overall and by type of treatment. Of these patients, 26 patients were splenectomized, while other patients were treated medically with thrombopoietin-receptor agonists (TPO-RAs) or immunosuppressive treatment. We also compared HRQoL of the splenectomized patients (internal cohort) with an external cohort of 63 splenectomized ITP patients and the general population. The median follow-up was 10 years (range 1-20). Splenectomized patients had a worse overall HRQoL profile than those who received medical therapy either with TPO-RAs or other treatments (OT), with clinically meaningful differences registered in several domains. These included physical functioning (Δ = - 17.0 and Δ = - 15.2, for TPO-Ras and OT, respectively, p = 0.065), role physical (Δ = - 9.7 and Δ = - 13.8, p = 0.483), and bodily pain (Δ = - 14.2 and Δ = - 18.8, p = 0.053). Compared to the general population, both internal and external splenectomized cohorts had an impaired HRQoL profile. Further studies on HRQoL in splenectomized ITP patients are needed to better understand the long-term impact of this surgical procedure.
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- 2021
10. Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib
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Fabio Stagno, Patrizia Pregno, Giovanni Caocci, Gianni Binotto, Robin Foà, Anna Sicuranza, Emilia Scalzulli, Francesca Pirillo, Mario Tiribelli, Isabella Capodanno, Antonella Gozzini, Massimiliano Bonifacio, Rossella Stella, Elisabetta Abruzzese, Massimo Breccia, Claudio Fozza, Gabriele Gugliotta, Giorgio La Nasa, Luigiana Luciano, Olga Mulas, Maria Pina Simula, Daniele Cattaneo, Mario Annunziata, Francesco Albano, Luigi Scaffidi, Fiorenza De Gregorio, Debora Luzi, Claudia Baratè, Malgorzata Monika Trawinska, Immacolata Attolico, Fabio Efficace, Sara Galimberti, Fausto Castagnetti, Monica Bocchia, Bruno Martino, Alessandra Iurlo, Caocci G., Mulas O., Capodanno I., Bonifacio M., Annunziata M., Galimberti S., Luciano L., Tiribelli M., Martino B., Castagnetti F., Binotto G., Pregno P., Stagno F., Abruzzese E., Bocchia M., Gozzini A., Albano F., Fozza C., Luzi D., Efficace F., Simula M.P., Scaffidi L., Barate C., De Gregorio F., Stella R., Gugliotta G., Pirillo F., Trawinska M.M., Sicuranza A., Cattaneo D., Attolico I., Scalzulli E., Iurlo A., Foa R., Breccia M., and La Nasa G.
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Male ,Arterial Occlusive Disease ,Triglyceride ,Gastroenterology ,Antineoplastic Agent ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,80 and over ,Cumulative incidence ,Chronic ,Aged, 80 and over ,Leukemia ,Incidence (epidemiology) ,Chronic myeloid leukemia ,Hematology ,General Medicine ,Middle Aged ,Lipoproteins, LDL ,Cholesterol ,030220 oncology & carcinogenesis ,Low-density lipoprotein ,Female ,Human ,medicine.drug ,Adult ,medicine.medical_specialty ,Lipoproteins ,Arterial occlusive event ,Antineoplastic Agents ,Arterial Occlusive Diseases ,Lower risk ,High cholesterol ,LDL ,03 medical and health sciences ,Young Adult ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,Triglycerides ,Aged ,Dyslipidemias ,business.industry ,Risk Factor ,Nilotinib ,medicine.disease ,Pyrimidines ,Dyslipidemia ,Pyrimidine ,chemistry ,BCR-ABL Positive ,business ,030215 immunology ,Myelogenous - Abstract
Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200mg/dL and LDL > 70mg/dL 3months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P= 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P< 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P= 0.008; HR = 3.5; 95% CI = 1.4–8.7 and P < 0.001; HR = 4.4; 95% CI = 2–9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins. Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.
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- 2020
11. Author response for 'Favourable outcome of chronic myeloid leukemia co‐expressing e13a2 and e14a2 transcripts, treated with nilotinib'
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Nicola Sgherza, Olga Mulas, Chiara Elena, Bruno Martino, Claudia Baratè, Ester Orlandi, Massimo Breccia, Anna Sicuranza, E Abruzzese, Robin Foà, Emilia Scalzulli, Monica Bocchia, Antonella Gozzini, Massimiliano Bonifacio, Malgorzata Monika Trawinska, S Galimberti, Daniele Cattaneo, Luigiana Luciano, Patrizia Pregno, Giorgio La Nasa, Francesco Albano, Fausto Castagnetti, A. Iurlo, Luigi Scaffidi, Gianni Binotto, Imma Attolico, Claudio Fozza, Mario Annunziata, Fiorenza De Gregorio, Giovanni Caocci, Maria Pina Simula, Gabriele Gugliotta, and Francesca Pirillo
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Oncology ,medicine.medical_specialty ,Nilotinib ,business.industry ,Internal medicine ,Medicine ,Myeloid leukemia ,business ,Outcome (game theory) ,medicine.drug - Published
- 2020
12. 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
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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.
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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.
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- 2020
13. Increased incidence of infection in patients with myelofibrosis and transfusion-associated iron overload in the clinical setting
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Olga Mulas, Maria Pina Simula, S Atzeni, Giorgia Mainas, Giovanni Caocci, Martina Pettinau, Silvia Ghiani, Emilio Usala, and Giorgio La Nasa
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Risk ,medicine.medical_specialty ,Ruxolitinib ,Iron Overload ,Gastroenterology ,Communicable Diseases ,Iron chelation ,Internal medicine ,Nitriles ,medicine ,Humans ,In patient ,Cumulative incidence ,Myelofibrosis ,Hematology ,business.industry ,Incidence (epidemiology) ,Incidence ,Transfusion Reaction ,medicine.disease ,Survival Rate ,Pyrimidines ,International Prognostic Scoring System ,Primary Myelofibrosis ,Pyrazoles ,business ,medicine.drug - Abstract
Transfusion-associated iron overload may lead to increased risk of infection, but its role in myelofibrosis (MF) has been scarcely explored. We evaluated 106 consecutive patients with primary or secondary MF. Up to 38% of patients were transfusion-dependent (TD) with a median of 14 RBC units received. Median observation time was 36 months (range 3–203). Forty-five percent of patients experienced one or more infectious episodes for a total of 69 infectious events, 13 (19%) of which were severe. The 60-month cumulative incidence of infection was 64.1 ± 6.5%. TD patients showed a higher incidence of infection (HR = 2.13, p = 0.019). Transfusion burden was markedly greater in TD patients with infectious complication (median 24 RBC units vs 15 RBC units; p = 0.012). The 60-month overall survival was 40 ± 5.9%. Lower International Prognostic Scoring System (IPSS) risk (p
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- 2020
14. Favorable outcome of chronic myeloid leukemia co-expressing e13a2 and e14a2 transcripts, treated with nilotinib
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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.
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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.
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- 2020
15. 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
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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.
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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.
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- 2020
16. Low Cholesterol, Low-Density Lipoprotein (LDL) and Triglycerides Plasma Levels Are Associated with Lower Risk of Arterial Occlusive Events in Chronic Myeloid Leukemia Patients Treated with Nilotinib
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Giovanni Caocci, Francesca Pirillo, Massimo Breccia, Emilia Scalzulli, Gabriele Gugliotta, Fabio Stagno, Chiara Elena, Mario Tiribelli, Patrizia Pregno, Alessandra Iurlo, Robin Foà, Bruno Martino, Claudia Baratè, Debora Luzi, Claudio Fozza, Anna Sicuranza, Daniele Cattaneo, Fiorenza De Gregorio, Gianni Binotto, Monica Bocchia, Luigi Scaffidi, Isabella Capodanno, Sara Galimberti, Massimiliano Bonifacio, Olga Mulas, Fausto Castagnetti, Maria Pina Simula, Malgorzata Monika Trawinska, Imma Attolico, Elisabetta Abruzzese, Rossella Stella, Luigiana Luciano, Francesco Albano, Antonella Gozzini, Mario Annunziata, and Giorgio La Nasa
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medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Lower risk ,medicine.disease ,Biochemistry ,Nilotinib ,Internal medicine ,medicine ,Rosuvastatin ,Cumulative incidence ,Risk factor ,Lipid modification ,Sokal Score ,business ,Dyslipidemia ,medicine.drug - Abstract
Introduction. New guidelines for the management of dyslipidemia and lipid modification in order to reduce the risk of cardiovascular (CV) events have been recently published by the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). New recommendations regarding the target value of plasma lipids in very high and high CV risk patients have been provided, in addition to an estimate of the CV risk with a new Systematic Coronary Risk Evaluation (SCORE) chart. Few data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib, and the association with arterial occlusive events (AOEs). We therefore analyzed a large real-life cohort of Italian patients with CML treated with nilotinib outside of clinical trials and evaluated the association between AOEs and plasma lipoproteins levels; moreover, we estimated the prognostic value of the new SCORE chart to predict AOEs. The secondary endpoint was to report the management of dyslipidemia in the clinical practice. Methods. We identified 233 adult patients with CML who were treated in 20 Italian centers with nilotinib. All patients were stratified into low to moderate (SCORE ≤ 5%) or high to very high (SCORE risk >5%) CV risk, according to the new version of the SCORE 2019. We recorded concentration levels of cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides at diagnosis of CML, before starting ponatinib and therefore after 3, 6 and 12 months of treatment. All AOEs (cerebrovascular, peripheral vascular and CV events excluding hypertension) were considered. Results. The median age was 50 years (range 20-88) and the Sokal score was intermediate-high in 45.5% of patients. The median follow-up was 5 years (range 3.4-10.5). Nilotinib was administered as first line of therapy in (72%) of cases or second or subsequent lines of treatment for inefficacy (20.9%) or intolerance (7.1%). At baseline, nilotinib was administered at the following doses: 800 mg/day in 9.3% of patients, 600 mg/day in 87% of patients, 400 mg/day in 3.1% of patients and 300mg in 0.6% of patients, respectively. The median time of drug exposure was 60 months (range 2-155). The 48-month cumulative incidence rate of AOEs was 14.1±2.7%. Patients with cholesterol plasma levels > 200 mg/dL and LDL >70 mg/dL at baseline and 3 months after starting nilotinib, showed a significantly higher incidence of AOEs (24.5±7.3% vs 11±2.7%, P=0.02 and 22.3±4.9% vs 5.9±2.6, P=0.003, respectively) Figure 1. Patients with triglycerides levels > 200 mg/dL 3 months after starting nilotinib, showed a significantly higher incidence of AOEs (56±20.5% vs 13.3±2.7%, P=0.011) Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (32.8.1±9% vs. 9±1%±2.6%, p=0.001). In multivariate analysis, statistical significance of cholesterol plasma levels > 200 mg/dL and LDL >70 mg/dL after 3 months and high-very-high SCORE was maintained (P=0.018, HR=3.4, 95% CI=1.2-9.4 and P=0.004, HR=3.5, 95% CI=1.5-8.2, respectively). Overall, 46 patients (20.5%) presented dyslipidemia at CML diagnosis and 65 (29%) at the start of treatment with nilotinib. Despite dyslipidemia, only 6 patients were taking statins during the treatment with nilotinib and only 5 started it after 3 months of nilotinib: 3 patients were treated with rosuvastatin and 2 with pravastatin. Conclusions. Our findings suggest that a proper control of dyslipidemia, keeping cholesterol and triglycerides plasma levels ≤ 200 mg/dL and LDL ≤70 mg/dL is associated with reduced risk of AOEs in CML patients treated with nilotinib. An under estimation of the clinical importance of elevated plasma lipids as a risk factor for AOEs events represents a possible issue in the real-life. Figure 1 Disclosures Abruzzese: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Galimberti:Incyte: Honoraria; Novartis: Speakers Bureau. Castagnetti:Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Pregno:Incyte-Italy,: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Novartis-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Pfizer-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports. Bocchia:CELGENE: Honoraria; Incyte: Honoraria. Gugliotta:Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria. Foà:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees.
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- 2020
17. Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second- and third-generation tyrosine kinase inhibitors
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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.
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- 2019
18. Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease
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Annamaria Petrungaro, Sonia Cirrincione, Marco Ruggeri, Fabio Forghieri, Fabio Efficace, Iolanda Vincelli, Nicola Cascavilla, Giovanni Caocci, Franco Mandelli, Paolo Ditonno, Maria Gabriella Mazzucconi, Francesco Cottone, Monica Carpenedo, Alessandra Borchiellini, Laura Scaramucci, Cristina Santoro, Gianluca Gaidano, Paola Fazi, Francesco Rodeghiero, Valeria Di Giacomo, Micaela Bergamaschi, Maria Pina Simula, and Alessandro Rambaldi
- Subjects
medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Physical fitness ,Hematology ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,030220 oncology & carcinogenesis ,Internal medicine ,Bayesian multivariate linear regression ,Propensity score matching ,Immunology ,Severity of illness ,Medicine ,Observational study ,business ,education ,030215 immunology - Abstract
The main objective of this study was to compare health-related quality of life (HRQOL) of primary immune thrombocytopenia (pITP) patients with that of general population, overall, and by patient group (i.e., newly diagnosed, persistent, and chronic patients). Fatigue was also investigated as a secondary objective. Overall, 424 adult patients were enrolled in a multicenter observational study and the control group consisted of a representative sample from the general population. Propensity score matching plus further multivariate linear regression adjustment was used to compare HRQOL outcomes between pITP patients and general population. Mean age of patients was 54 years. Of those with HRQOL assessment, 99 patients (23.6%) were newly diagnosed, 53 (12.6%) were persistent, and 268 (63.8%) were chronic pITP patients. Comparison by patient group versus their respective peers in the general population revealed greater impairments in persistent pITP patients. Persistent pITP patients reported clinically meaningful impairments in physical functioning (-15; 95% CI -24.1 to -5.8; P = 0.002), social functioning (-15.3; 95% CI -25.5 to -5.1; P = 0.004), role physical (-28.4; 95% CI -43.1 to -13.7; P
- Published
- 2016
19. Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
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Martino Deidda, Olga Mulas, Claudia Fattuoni, Marianna Greco, Antonio Noto, Christian Cadeddu Dessalvi, Giorgio La Nasa, Daniele Cocco, Maria Pina Simula, Giuseppe Mercuro, and Giovanni Caocci
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0301 basic medicine ,cardiovascular adverse events ,lcsh:Medicine ,Pharmacology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,tyrosine kinase inhibitors ,medicine ,Tyrosine ,business.industry ,lcsh:R ,Chronic myeloid leukemia ,Ponatinib ,Myeloid leukemia ,Imatinib ,General Medicine ,Ornithine ,respiratory tract diseases ,Dasatinib ,030104 developmental biology ,chemistry ,Nilotinib ,GC-MS metabolomics ,030220 oncology & carcinogenesis ,business ,Tyrosine kinase ,medicine.drug - Abstract
Background: Cardiovascular adverse events (CV-AEs) are considered critical complications in chronic myeloid leukemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (TKIs). The aim of our study was to assess the correlation between metabolic profiles and CV-AEs in CML patients treated with TKIs. Methods: We investigated 39 adult CML patients in chronic-phase (mean age 49 years, range 24&ndash, 70 years), with no comorbidities evidenced at baseline, who were consecutively identified with CML and treated with imatinib, nilotinib, dasatinib, and ponatinib. All patients performed Gas-Chromatography-Mass-Spectrometry-based metabolomic analysis and were divided into two groups (with and without CV-AEs). Results: Ten CV-AEs were documented. Seven CV-AEs were rated as 3 according to the Common Toxicity Criteria, and one patient died of a dissecting aneurysm of the aorta. The patients&rsquo, samples were clearly separated into two groups after analysis and the main discriminant metabolites were tyrosine, lysine, glutamic acid, ornithine, 2-piperdinecarboxylic acid, citric acid, proline, phenylalanine, threonine, mannitol, leucine, serine, creatine, alanine, and 4-hydroxyproline, which were more abundant in the CV-AE group. Conversely, myristic acid, oxalic acid, arabitol, 4-deoxy rithronic acid, ribose, and elaidic acid were less represented in the CV-AE group. Conclusions: CML patients with CV-AEs show a different metabolic profile, suggesting probable mechanisms of endothelial damage.
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- 2020
20. Metabolomics Profile of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
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Olga Mulas, Giuseppe Mercuro, Marianna Greco, Daniele Cocco, Maria Pina Simula, Christian Cadeddu, Claudia Fattuoni, Antonio Noto, Giovanni Caocci, Martino Deidda, and Giorgio La Nasa
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business.industry ,Immunology ,Ponatinib ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,Dasatinib ,chemistry.chemical_compound ,Imatinib mesylate ,chemistry ,Nilotinib ,Cancer research ,medicine ,Tyrosine ,business ,Adverse effect ,Tyrosine kinase ,medicine.drug - Abstract
Background. Cardiovascular adverse events (CV-AE) are emerging complications in chronic myeloid leukemia (CML) patients treated with second and third generation tyrosine kinase inhibitors (TKIs). Despite the importance of CV risk factors,predictive CV-AE biomarkers are still lacking. Further understanding of the molecular pathways underlying CV-AE may promote novel strategies to prevent its initiation prior to clinical disease. In this scenario, the use of a novel tool such as metabolomics may be useful for the identification of new metabolic pathways related to CV-AE. Metabolites are the output of cellular metabolism, accounting for expression and activity of genes, transcripts, and proteins, and offering unique insights into small molecule regulation. For the first time we evaluated the correlation between CV-AE and metabolomic profile in CML patients treated with TKIs. Methods. We considered 39 adult CP-CML patients (mean age 49, range 24-70), without comorbidity at baseline, consecutively diagnosed and treated with imatinib, dasatinib nilotinib and ponatinib, at the Haematology Unit of "Businco Hospital", Cagliari, Italy. All patients underwent a metabolomic profile detection, after CV-AE or during follow-up, and were stratified in 2 groups (with or without CV-AE). Plasma samples were collected and acquired chromatogram was analysed by means of the free software AMDIS (Automated Mass Spectral Deconvolution and Identification System; http://chemdata.nist.gov/mass-spc/amdis) that identified each peak by comparison of the relative mass spectra and the retention times with those stored in an in-house made library comprising 255 metabolites. Data were investigated by applying the supervised multivariate statistical approach OPLS-DA (Orthogonal partial least square discriminant analysis) (SIMCA, version 13.0, Umetrics, Umea, Sweden). Results. The mean follow-up since CML diagnosis was 3.7 years (range 0.9-5); 22 (56.4%) patients were treated frontline, while 17 (43.5%) underwent second or subsequent TKI lines of treatments. The reason for switching was inefficacy in 15.3% and intolerance in 28.2%. At CV-AE or last follow-up 16 (41%) patients were treated with imatinib, 8 (20.5%) with dasatinib, 14 (35.8%) with nilotinib and 1 patient with ponatinib (2.7%). Overall, 17 CV-AE were recorded: 7 cases of hypercholesterolemia, 5 pleural or pericardial effusions, one episode of hypertension and 4 cardiac events (atrial fibrillation,ST-segment elevation myocardial infarction, reduction of cardiac ejection fraction and dissecting aneurysm of the aorta); 7 CV-AE were graded as 3 according to the common toxicity criteria and one patient died from dissecting aneurysm of the aorta). The 60-month cumulative CV-AE incidence was 54.4±9.1%. The mean time between the start of the treatment and the occurrence of a CV-AE was 44.4 months (range 19-60). OPLS-DA showed that patient's samples were clearly separated into 2 groups indicating that CV-AE patients (blue dots) presented a markedly distinct metabolic profile compared with patients without CV-AE (green dots); (figure 1). The parameters of the model were R2Y = 0.76 and Q2 = 0.44. To validate the OPLS-DA model, a permutation was performed resulting statistically significant (p=0,002). The main discriminant metabolites were tyrosine, lysine, ornithine, glutamic acid, 2-piperdincarboxylic acid, proline, citric acid, phenylalanine, mannitol, threonine, leucine, creatine, serine, 4-hydroxyproline, and alanine (more represented in CV-AE group); while unknown 204, myristic acid, arabitol, oxalic acid, 4-deoxyrithronic acid, elaidic acid and ribose resulted less expressed in CV-AE group. Conclusions. This exploratory study showed different metabolomic profile of CML patients with CV-AE underwent TKI treatment, suggesting possible mechanisms of endothelial damage mediated by the accumulation of metabolites. Tyrosine, highly expressed in the CV-AE CML group, is a reliable marker of oxidative stress in various acute and chronic diseases.Metabolomics research has considerable potential for translating the metabolic fingerprint into personalized therapeutic strategies. These preliminary data should be confirmed in prospective clinical trials. Figure 1 Disclosures No relevant conflicts of interest to declare.
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- 2019
21. Systemic Mastocytosis with Associated Primary Myelofibrosis
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Sandra Orrù, Roberto Mascia, Maria Pina Simula, Margherita Deidda, Maria Pina Barca, Giovanni Caocci, Sonia Nemolato, Giorgio La Nasa, and Marianna Greco
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medicine.medical_specialty ,Hematology ,business.industry ,Internal medicine ,Images ,medicine ,Systemic mastocytosis ,Myelofibrosis ,medicine.disease ,business ,Dermatology ,Human genetics - Published
- 2019
22. PB1999 SECOND MALIGNANCIES IN LYMPHOMA SURVIVORS: A SINGLE CENTER EXPERIENCE
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G. La Nasa, Maria Pina Simula, Stefania Massidda, and A.M. Mamusa
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Hematology ,Single Center ,business ,medicine.disease ,Lymphoma - Published
- 2019
23. Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease
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Fabio, Efficace, Franco, Mandelli, Paola, Fazi, Cristina, Santoro, Gianluca, Gaidano, Francesco, Cottone, Alessandra, Borchiellini, Monica, Carpenedo, Maria Pina, Simula, Valeria, Di Giacomo, Micaela, Bergamaschi, Iolanda Donatella, Vincelli, Francesco, Rodeghiero, Marco, Ruggeri, Laura, Scaramucci, Alessandro, Rambaldi, Nicola, Cascavilla, Fabio, Forghieri, Annamaria, Petrungaro, Paolo, Ditonno, Giovanni, Caocci, Sonia, Cirrincione, and Maria Gabriella, Mazzucconi
- Subjects
Adult ,Male ,Purpura, Thrombocytopenic, Idiopathic ,Mental Health ,Physical Fitness ,Surveys and Questionnaires ,Quality of Life ,Humans ,Female ,Middle Aged ,Severity of Illness Index ,Fatigue ,Aged - Abstract
The main objective of this study was to compare health-related quality of life (HRQOL) of primary immune thrombocytopenia (pITP) patients with that of general population, overall, and by patient group (i.e., newly diagnosed, persistent, and chronic patients). Fatigue was also investigated as a secondary objective. Overall, 424 adult patients were enrolled in a multicenter observational study and the control group consisted of a representative sample from the general population. Propensity score matching plus further multivariate linear regression adjustment was used to compare HRQOL outcomes between pITP patients and general population. Mean age of patients was 54 years. Of those with HRQOL assessment, 99 patients (23.6%) were newly diagnosed, 53 (12.6%) were persistent, and 268 (63.8%) were chronic pITP patients. Comparison by patient group versus their respective peers in the general population revealed greater impairments in persistent pITP patients. Persistent pITP patients reported clinically meaningful impairments in physical functioning (-15; 95% CI -24.1 to -5.8; P = 0.002), social functioning (-15.3; 95% CI -25.5 to -5.1; P = 0.004), role physical (-28.4; 95% CI -43.1 to -13.7; P 0.001), role emotional (-23.9; 95% CI -40.1 to -7.7; P = 0.004), and mental health scales (-11.3; 95% CI -21.2 to -1.4; P = 0.026) of the SF-36 questionnaire. Higher fatigue severity was associated with lower physical and mental HRQOL outcomes. Our findings suggest that the burden of the disease and treatment might depend on the disease phase and that persistent pITP patients are the most vulnerable subgroup. Am. J. Hematol. 91:995-1001, 2016. © 2016 Wiley Periodicals, Inc.
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- 2016
24. CD4+ and CD8+ T-Cell Skewness in Classic Kaposi Sarcoma
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Maurizio Roberto Longinotti, Antonio Angeloni, Simonetta Pardini, Patrizia Virdis, Simona Ceccarelli, Francesca Cottoni, Giovanna Corda, Sara Pruneddu, Maria Pina Simula, Antonio Galleu, Salvatore Contini, and Claudio Fozza
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CD4-Positive T-Lymphocytes ,Male ,Cancer Research ,medicine.drug_class ,Receptors, Antigen, T-Cell ,Complementarity determining region ,CD8-Positive T-Lymphocytes ,Monoclonal antibody ,Antibodies, Viral ,lcsh:RC254-282 ,Immune system ,Antigen ,medicine ,Cytotoxic T cell ,Humans ,Lymphocyte Count ,Sarcoma, Kaposi ,Alleles ,Aged ,Aged, 80 and over ,biology ,T-cell receptor ,Homozygote ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Complementarity Determining Regions ,Case-Control Studies ,Immunology ,Herpesvirus 8, Human ,biology.protein ,Female ,Antibody ,CD8 ,Research Article - Abstract
It is widely accepted that a deranged immune system plays a key role in the onset and evolution of classic Kaposi sarcoma (CKS). Nevertheless, the usage of the T-cell receptor (TCR) β-variable (BV) chain repertoire expressed by peripheral blood lymphocytes in patients with CKS is still unknown. With the aim of providing some further insights into the complex role of the immune system in CKS pathogenesis, we performed an extensive analysis of the TCR BV repertoire in both CD4(+) and CD8(+) T cells in 30 human herpesvirus 8-positive Sardinian patients with CKS and an equal number of age-matched healthy controls. We used a panel of monoclonal antibodies covering approximately 70% of human BV subfamilies and third complementarity determining region (CDR3) spectratyping. Patients with CKS showed an increased frequency of BV expansions in both CD4(+) and CD8(+) lymphocytes, with no prevalent clones. On spectratyping analysis, most of the 720 BV CDR3 profiles obtained from both CD4(+) and CD8(+) T cells in patients with CKS were skewed. In particular, the surprising increase of BV skewing observed in CD4(+) lymphocytes mimics the pattern of progressive TCR BV narrowing described in responses to persistent viral antigen stimulations. Our findings support the hypothesis that CKS evolution is associated with inadequate activation rather than impairment of the immune system.
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- 2012
25. Marginal zone B-cell lymphoma arising in donor cells in a Hepatitis-C virus infected patient over 20 years after allogeneic bone marrow transplantation
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Francesca Zaccheddu, Martina Pettinau, Emanuele Angelucci, Maria Pina Simula, Maria Giuseppina Cabras, Angela Maria Mamusa, Andrea Bacigalupo, and F Culurgioni
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Cancer Research ,Marrow transplantation ,business.industry ,Hepatitis C virus ,Hematology ,medicine.disease_cause ,medicine.disease ,Oncology ,Infected patient ,Immunology ,medicine ,Marginal zone B-cell lymphoma ,Autogenous bone ,business - Published
- 2008
26. Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib
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Giorgio Lambertenghi Deliliers, F. Efficace, P. Leoni, Fabio Stagno, Luigiana Luciano, Michele Baccarani, Massimo Breccia, Giorgina Specchia, Maria Pina Simula, Franco Mandelli, Giuliana Alimena, Dino Veneri, Marco Vignetti, Diamante Turri, Bruno Martino, R. Di Lorenzo, M. Bergamaschi, Melissa Dabusti, Giovanni Rosti, Carmen Fava, Claudia Baratè, Luciano Levato, Alessandro Rambaldi, Simona Sica, and Francesco Cottone
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Oncology ,Male ,Cancer Research ,Piperazines ,Quality of life ,Musculoskeletal Pain ,hemic and lymphatic diseases ,80 and over ,Young adult ,Chronic ,Aged, 80 and over ,Leukemia ,Fatigue Syndrome, Chronic ,Myeloid leukemia ,Hematology ,Limiting ,Middle Aged ,Fatigue Syndrome ,Benzamides ,Imatinib Mesylate ,Female ,medicine.symptom ,medicine.drug ,Adult ,medicine.medical_specialty ,Antineoplastic Agents ,Young Adult ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,Social Behavior ,Aged ,Muscle Cramp ,Health related quality of life ,business.industry ,Imatinib ,Chronic fatigue ,Health Surveys ,Surgery ,Settore MED/15 - MALATTIE DEL SANGUE ,Cross-Sectional Studies ,Pyrimidines ,Multivariate Analysis ,Quality of Life ,BCR-ABL Positive ,business ,Muscle cramp ,Myelogenous - Abstract
Health-related quality of life (HRQOL) is an important goal of therapy for chronic myeloid leukemia (CML) patients treated with current molecular-targeted therapies. The main objective of this study was to investigate factors associated with long-term HRQOL outcomes of CML patients receiving imatinib. Analysis was performed on 422 CML patients recruited in an observational multicenter study. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Key socio-demographic and clinical data were investigated for their association with HRQOL outcomes. Chronic fatigue and social support were also investigated. Univariate and multivariate linear regression analyses were used to identify independent factors associated with HRQOL outcomes. Fatigue was the only variable showing an independent and consistent association across all physical and mental HRQOL outcomes (P0.01). Differences between patients reporting low versus high fatigue levels were more than eight and seven times the magnitude of a clinically meaningful difference, respectively, for the role physical (Δ=70 points) and emotional scale (Δ=63 points) of the SF-36. Fatigue did not occur as an isolated symptom and was most highly correlated with musculoskeletal pain (r=0.511; P≤0.001) and muscular cramps (r=0.448; P≤0.001). Chronic fatigue is the major factor limiting HRQOL of CML patients receiving imatinib.
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- 2013
27. Health-Related Quality of Life in Patients with Primary Immune Thrombocytopenia (pITP): Investigating Differences Amongst Newly Diagnosed, Persistent and Chronic Pitp Patients
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Paolo Ditonno, Maria Pina Simula, Cristina Santoro, Francesco Nobile, Francesco Cottone, Ivana Pierri, Franco Mandelli, Nicola Cascavilla, Paola Fazi, Fabio Efficace, Alessandra Borchiellini, Valeria Di Giacomo, Annamaria Petrungaro, Sonia Cirrincione, Francesco Rodeghiero, Fabio Forghieri, Maria Gabriella Mazzucconi, Alessandro Rambaldi, Giorgio La Nasa, Laura Scaramucci, Gianluca Gaidano, and Monica Carpenedo
- Subjects
Pediatrics ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Mental health ,Comorbidity ,law.invention ,Randomized controlled trial ,Quality of life ,law ,Propensity score matching ,Medicine ,Marital status ,Clinical significance ,business ,education - Abstract
Introduction: Very little is known about health-related quality of life (HRQOL) of patients diagnosed with primary Immune Thrombocytopenia (pITP). Also, the paucity of available data mainly stems from patients enrolled in randomized controlled trials thus limiting generalizability of findings to patients routinely seen in real world practice. Aim: The main objective of this study is to compare HRQOL of pITP patients with that of their peers from the general population and to investigate whether HRQOL differences exist among those classified as (Rodeghiero et al, Blood. 2009 Mar 12;113(11):2386-93): newly diagnosed, persistent and chronic pITP patients. Methods: Adult patients with pITP were consecutively enrolled, regardless of therapy, in 25 centers. All patients were invited by their treating physicians in the hospital. Consenting patients were requested to complete a battery of patient-reported outcome (PRO) questionnaires. The primary HRQOL outcome measure was the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). It consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). To minimize possible bias in comparisons of pITP patients HRQOL outcomes to general population norms, a propensity score matching approach plus further regression adjustment was adopted to select the best possible case-control pairs. The group of potential controls was a representative sample of 1997 adults without the disease from a previous study which provided SF-36 population norms. Controls from these data were matched to pITP patients by an optimal nearest-neighbour matching algorithm based on age, sex, education, and geographic area. Multiple linear regression analyses were performed on the matched dataset to compute adjusted mean differences (α=0.05), using selected a priori key HRQOL confounders as covariates: age, sex, education, geographic area, and marital status. Effect sizes were computed and clinical significance of mean scores SF-36 differences was also estimated. Results: Out of 424 patients invited to participate, 420 returned the questionnaires (99% compliance). At study participation, mean age of patients was 54 years (range 18-89) with the majority being women (N=264, 64%). The mean platelet count at diagnosis was 27.6 x109/L and the mean platelet count at last medical visit, before the HRQOL assessment, was 119 x109/L. Two-hundred twenty patients (50%) had at least 1 comorbidity. At the time of HRQOL assessment there were 82%, 64% and 44% of patients receiving active treatments, respectively in the newly diagnosed, persistent and chronic pITP group. Splenectomy was performed in 8% and 22% of the persistent and chronic pITP patients, respectively. No statistically significant differences existed among the three disease groups with regard to age, gender and presence of comorbidity. When compared with their peers in the general population, worse statistically significant outcomes (P Conclusions: Persistent pITP patients are those experiencing the most important limitations in both physical and mental HRQOL domains with respect to their peers from the general population. This information can help physicians to pay special attention to this patient group in their daily clinical practice. Disclosures Gaidano: Celgene: Research Funding; MorphoSys; Roche; Novartis; GlaxoSmithKline; Amgen; Janssen; Karyopharm: Honoraria, Other: Advisory boards. Rodeghiero:Celgene Corporation: Honoraria, Research Funding.
- Published
- 2015
28. TCRBV20S1 polymorphism does not influence the susceptibility to type 1 diabetes and multiple sclerosis in the Sardinian population
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Maria Pina Simula, Claudio Fozza, Francesco Cucca, Maristella Pitzalis, Maurizio Roberto Longinotti, Salvatore Contini, Antonio Galleu, Silvana Bonfigli, and Magdalena Zoledzieska
- Subjects
Multiple Sclerosis ,Immunology ,Population ,Receptors, Antigen, T-Cell ,Biology ,Gene Frequency ,Polymorphism (computer science) ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Allele frequency ,education.field_of_study ,Polymorphism, Genetic ,Multiple sclerosis ,medicine.disease ,Null allele ,Stop codon ,Human genetics ,Founder Effect ,Diabetes Mellitus, Type 1 ,Italy ,Mutation ,Founder effect - Abstract
Among the different T-cell receptor (TCR) BV20S1 polymorphisms, nucleotide substitution at position 524 results in the introduction of a stop codon, whose potential functional relevance is still unknown. We have recently showed in Sardinian subjects the most elevated allele frequency ever reported worldwide for this "null allele" (0.44). As this variant generates a gap in the TCR repertoire, this preliminary finding prompted us to further analyze the role of this polymorphism in the susceptibility to type 1 diabetes (T1D) and multiple sclerosis (MS), which are extremely common in this population. With this aim, we evaluated the influence of the TCRBV20S1 polymorphism by assessing it with the transmission disequilibirum test (TDT) in 652 T1D and 616 MS families, without detecting any significant difference. We conclude that the high frequency of this null allele in Sardinia is not directly related to the high incidence of these autoimmune diseases observed in this founder population.
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- 2011
29. Health-Related Quality of Life In Patients with Chronic Myeloid Leukemia Undergoing First Line Treatment with Imatinib for at Least Three Years Compared with the General Population. A Multicenter Study Including 448 Patients
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Luigia Luciano, Massimo Breccia, Luciano Levato, Alessandro Rambaldi, Fabio Efficace, Diamante Turri, Antonio Cuneo, Alfonso Zaccaria, Giuseppe Saglio, Pietro Leoni, Filippo Gherlinzoni, Antonella Russo Rossi, Simonetta Pardini, Giuliana Alimena, Franco Mandelli, Giorgio Lambertenghi Deliliers, Maria Pina Simula, Michele Baccarani, Francesco Cottone, Claudia Baratè, Francesco Nobile, Giuseppe Leone, Marco De Gobbi, Giuseppe Fioritoni, Dino Veneri, Marco Vignetti, Francesco Di Raimondo, Gianantonio Rosti, and Mario Tiribelli
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education.field_of_study ,Pediatrics ,medicine.medical_specialty ,Activities of daily living ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Comorbidity ,Mental health ,Quality of life ,Survivorship curve ,Medicine ,Clinical significance ,education ,business ,Disease burden - Abstract
Abstract 2273 Background: While Imatinib (IM) has revolutionized treatment for chronic myeloid leukemia (CML), demonstrating outstanding survival figures, currently no data exist on mid to long term impact of disease burden and therapy from the patients’ perspective. Aim: The main objective of this study is to identify specific limitations of quality of life (QoL) in CML survivors who are undergoing first line treatment with IM in comparison with controls from the general population. Patient-reported symptom prevalence was also investigated. Patients and methods: Patients were recruited in 26 centers, randomly selected to geographically represent the whole study country. Patients selection criteria included: being in treatment with IM for at least three years and being in complete cytogenetic response at the time of study entry. All patients were invited by their treating physicians in the hospital to participate and all consenting patients were requested to complete a Health Survey Packet at home. Pre-paid reply envelopes were also provided with the request to send back completed Surveys to an independent National coordinating Data Center. Generic QoL was assessed with the SF-36 that consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). All scales ranging between 0 and 100 with higher scores representing better outcomes. A previously devised patient-reported CML Symptom Checklist was used to investigate 9 symptoms of possible major concern in these patients. Mean SF-36 scores were compared to available national general population reference values and all analyses were adjusted for age and gender. Statistical comparisons were all adjusted for multiple testing. Differences in mean scores were expressed in Cohen effect sizes (ES; with 0.2, 0.5, and 0.8 indicating small, medium, and large ES, respectively) and clinical significance. Results: Between March and December 2009, 448 patients were recruited in a large national-based survivorship project. Patients’ compliance was optimal with 94% of patients (N=421) returning a valid Health Survey Packet to the National coordinating Data center. At study participation, mean age of patients was 56 years (59% male and 41% female) and median time of IM therapy was 5 years. Seventy-seven percent of patients were receiving standard dose of 400 mg and 43% had at least one comorbidity. Age and gender adjusted comparisons with general population norms revealed worse outcomes for the following scales: RP (P75 years) suggested an almost uniform pattern in all scales with worse outcomes between CML patients and population controls among the youngest groups. GH was significantly worse in younger patients (55-64) (P=.03; ES=0.4) and no differences were found in the older age groups compared with population norms. Prevalence of reported symptoms (with any level of concern) was: fatigue (82%); problems with muscular cramps (78%); problems with musculoskeletal pain (72%); problems with edema (70%); skin problems (47%); diarrhea (43%); headache (39%); abdominal discomfort and nausea (28%). Conclusion: This study suggests that while still being on treatment with IM for years, CML patients might expect to have a QoL profile broadly similar to that of general population in many areas. However, role limitations (i.e., in work or other regular daily activities) due to physical health seem the major constraint faced by these patients; there is also an indication that younger patients might be those experiencing major limitations. Additional analyses will be undertaken to ascertain the impact of symptoms and other laboratory and clinical data on specific QoL domains. Such unique patient-reported data supplements conventional information on clinical efficacy of IM and may support both clinicians and patients in making more informed treatment decisions in this area. Disclosures: Rosti: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol M. Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau.
- Published
- 2010
30. Patients with myelodysplastic syndromes display several T-cell expansions, which are mostly polyclonal in the CD4(+) subset and oligoclonal in the CD8(+) subset
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Maurizio Roberto Longinotti, Claudio Fozza, Patrizia Virdis, Maria Pina Simula, Salvatore Contini, Silvana Bonfigli, and Antonio Galleu
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Adult ,CD4-Positive T-Lymphocytes ,Cancer Research ,Lymphocyte ,T cell ,Receptors, Antigen, T-Cell, alpha-beta ,chemical and pharmacologic phenomena ,Complementarity determining region ,Human leukocyte antigen ,Biology ,CD8-Positive T-Lymphocytes ,Antigen ,Genetics ,medicine ,Cytotoxic T cell ,Humans ,Molecular Biology ,Aged ,Cell Proliferation ,Aged, 80 and over ,T-cell receptor ,Cell Biology ,Hematology ,Middle Aged ,Flow Cytometry ,Complementarity Determining Regions ,medicine.anatomical_structure ,Case-Control Studies ,Myelodysplastic Syndromes ,Immunology ,Female ,CD8 ,T-Lymphocytes, Cytotoxic - Abstract
Objective Immune dysregulation plays a role in the pathophysiology of myelodysplastic syndromes (MDS), as T-cell clones seem to be involved in the inhibition of hematopoietic precursors. The purpose of this study was to analyze the T-cell receptor (TCR) repertoire of MDS patients, focusing on the third complementarity determining region (CDR3) pattern of their CD4 + and CD8 + lymphocyte expansions. Materials and Methods The study involved 30 patients and 15 age-matched controls. The β -variable ( β V) subfamily flow-cytometry analysis was performed on peripheral CD4 + and CD8 + T-cells. Spectratyping TCR-CDR3 analysis was carried out on isolated helper and cytotoxic T lymphocytes after immunomagnetic separation and reverse-transcriptase polymerase chain reaction. Results We first identified by flow cytometry an increased frequency of expanded βVs in both CD4 + and CD8 + T-cells in MDS patients. We then showed, by spectratyping, that the CDR3 profile was mostly Gaussian in their CD4 + T cells, whereas CD8 + T cells usually showed skewed or oligoclonal CDR3 regions. When we compared spectratyping and flow-cytometry findings in each patient, we showed that most CD4 + lymphocyte expansions detected by flow cytometry had Gaussian CDR3 profiles, whereas most CD8 + expansions were oligoclonal. Conclusion We confirm that in MDS patients the TCR- β V repertoire is overall extremely contracted, especially in cytotoxic T cells. This pattern is mainly determined by selective proliferations of both helper and cytotoxic T cells, which are, however, mostly polyclonal in the former and oligoclonal in the latter. Such a difference, possibly related to the different human leukocyte antigen restriction, could reflect the selective involvement of cytotoxic T cells either in the anti-tumor immune surveillance or in an autoreactive aggression toward hematopoietic precursors.
- Published
- 2009
31. Health-Related Quality of Life in Patients with Primary Immune Thrombocytopenia Compared with the General Population
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Paolo de Fabritiis, Julia Daragjati, Salvatore Soldati, Monica Carpenedo, Piercarla Schinco, Alessandra Borchiellini, Erminia Baldacci, Fabio Efficace, Paola Fazi, Alessandro Rambaldi, Maria Gabriella Mazzucconi, Paolo Ditonno, Maria Pina Simula, Giovanni Caocci, Gianluca Gaidano, Francesco Rodeghiero, and Franco Mandelli
- Subjects
education.field_of_study ,Pediatrics ,medicine.medical_specialty ,Activities of daily living ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Comorbidity ,Mental health ,Quality of life ,Sample size determination ,medicine ,Clinical endpoint ,Observational study ,education ,business - Abstract
Abstract 2056 Background: Recent international guidelines (Rodeghiero F, et al. Blood 113:2386–93, 2009) emphasize the importance of health-related quality of life (HRQOL) in patients with primary immune thrombocytopenia (pITP) and are advocating for more research in this area. However, very little research has been conducted on HRQOL of these patients. Aim: The main objective of this study was to identify specific limitations of HRQOL in pITP patients (ie, chronic, persistent and newly diagnosed patients) in comparison with their peers from the general population. Also, socio-demographic and clinical factors were considered to evaluate HRQOL impairment. Patients and Methods: Data were gathered through an ongoing multicenter observational study that recruits p-ITP patients. HRQOL was the primary endpoint of the study and was assessed with Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) that consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). All scales ranging between 0 and 100 with higher scores representing better outcomes. Two summary scores, namely the physical component summary (PCS) and the mental component summary (MCS) are derived from a weighted combination of the eight scales. Mean SF-36 scores were compared to available national general population reference values and analyses were adjusted for age and gender. Based on previous research, eight points were considered to be a minimally important difference (MID) for the first eight SF-36 scales, while a difference of two points was judged as MID for the PCS and the MCS scores. A score difference at least equal to MID was considered as a clinically meaningful difference. Socio-demographic, clinical and laboratory data were also collected to investigate their association with HRQOL outcomes. Univariate and multivariate linear regression analyses were used. Results: To date of the 256 pITP patients included in this study, 69%, 16% and 15%, were diagnosed with chronic, persistent and newly diagnosed pITP respectively. Present analysis is based on 175 patients with HRQOL data currently available. At study participation, mean age of patients was 54 years (67% female and 33% male). At least one comorbidity was present in 53% of patients. The median time from initial diagnosis to study entry was 0.3, 8 and 77 months respectively for newly diagnosed, persistent and chronic patients. Age and gender adjusted comparisons with general population norms revealed worse outcomes for the following scales: RP (P65 years) suggested an almost uniform pattern in all scales with worse outcomes between pITP patients and population controls among the youngest groups. Statistically and clinically meaningful differences (ie, >8 points) were found in five out of the eight scales of the SF-36 in the youngest group of patients (18–54 years), when compared with their peers, while these differences were not present in the other age group categories. Comorbidity was the main factor influencing HRQOL by independently predicting worse HRQOL outcomes across all domains of the SF-36. SF-36 mean score differences in patients with or without comorbidity, were more than twice the magnitude of a clinically meaningful difference for PF and RP, being respectively: 69.7 vs. 87 and 51.3 vs. 68 points. Conclusions: This study suggests that HRQOL of p-ITP patients is far from optimal. In particular, role limitations (i.e., in work or other daily activities) due to physical health seems the major constraint faced by these patients when compared to their peers in the general population. Comorbidity seems the major factor associated with a poorer HRQOL profile. These findings need to be confirmed with a larger sample size and will eventually help guide the development of patient-centered supportive care programs. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
32. Fatigue Is the Major Aspect Compromising Health-Related Quality of Life of Chronic Myeloid Leukemia Patients Receiving Long-Term Imatinib Therapy
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Marco Vignetti, Carmen Fava, Alessandro Rambaldi, Anna Rita Scortechini, Massimo Breccia, Fabio Efficace, Michele Baccarani, Simona Sica, Luciano Levato, Francesco Cottone, Franco Mandelli, Diamante Turri, Luigia Luciano, Roberto Di Lorenzo, Giorgina Specchia, Dino Veneri, Gianantonio Rosti, Bruno Martino, Micaela Bergamaschi, Maria Pina Simula, Fabio Stagno, Claudia Baratè, Giuliana Alimena, Melissa Dabusti, and Giorgio Lambertenghi Deliliers
- Subjects
medicine.medical_specialty ,education.field_of_study ,Palliative care ,Multivariate analysis ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,Biochemistry ,Mental health ,Social support ,Quality of life ,Quartile ,Physical therapy ,medicine ,Observational study ,Psychiatry ,education ,business - Abstract
Abstract 4234 Background: Whilst recent data indicates that survival of chronic myeloid leukemia (CML) patients, who are in complete cytogenetic response (CCyR) with Imatinib therapy, is not statistically significantly different from that of the general population, health-related quality of life (HRQOL) differences do exist. However, to date no study has investigated the predictive factors of long-term HRQOL outcomes of CML patients treated with TKIs. Aim: The main objective of this study was to investigate potential key factors associated with long-term HRQOL outcomes of CML patients in CCyR treated with first line Imatinib therapy. A secondary objective was to investigate the relationships between fatigue and other treatment related symptoms and describe how fatigue relates to socio-demographic and clinical data. Patients and Methods: Analysis was performed on 422 CML patients recruited in an observational multicenter study. Median time in treatment with Imatinib was five years (range: 3 to 9.3 years). HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). This questionnaire consists of 36 items covering eight generic HRQOL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). Predictor variables investigated included, fatigue and social support, measured with two psychometrically robust questionnaires, that is the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and the multidimensional scale of perceived social support (MSPSS) scale. Other CML treatment related symptoms were measures with an ad hoc CML symptom checklist. Key socio-demographic and clinical data including, age, gender, education, Sokal risk, response to therapy and duration of treatment, were also considered. Univariate and multivariate regression analyses were used to identify a set of independent predictors for each SF-36 scale, via a stepwise selection procedure. Results: In the multivariate analysis the following factors independently predicted a better PF: younger age (P Conclusion: To our knowledge, this was the first investigation to date of factors associated with long-term HRQOL in CML patients being treated with an oral anticancer-targeted therapy. Our findings suggest that although responding to Imatinib therapy, long-term patient's HRQOL is greatly affected by fatigue levels. Also, our results suggest that symptom management is crucial to the possible improvement of HRQOL outcomes. Legend: Low, Low-Medium, Medium-High and High correspond respectively to the 4th (75th to 100th percentile), 3rd, 2nd and 1st (0th to 25th percentile) quartile of FACIT-Fatigue scale. On this scale, the higher the score the lower is the level of fatigue. Disclosures: Efficace: Bristol Myers Squibb: Consultancy; Novartis: Research Funding. Baccarani:Novartis : Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer and Ariad: Honoraria. Breccia:Bristol Myers Squibb: Consultancy; Novartis: Consultancy. Rosti:Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria. Alimena:Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Turri:Novartis: Consultancy, Novartis Other; Bristol Myers Squibb: Bristol Myers Squibb, Bristol Myers Squibb Other, Consultancy.
- Published
- 2012
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