32 results on '"Sportoletti P"'
Search Results
2. P664: GRADING QUALITY OF EVIDENCE AND STRENGTH OF RECOMMENDATIONS FOR THE TREATMENT OF RELAPSED/REFRACTORY CLL.
- Author
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Molica, S., Patti, C., Sportoletti, P., Chiarenza, A., Giordano, A. M., Chiurazzi, F., Di Renzo, N., Musto, P., Pane, F., Di Raimondo, F., Trentin, L., Mauro, F. R., and Giannarelli, D.
- Published
- 2022
- Full Text
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3. P660: SEROLOGIC RESPONSE TO THE SECOND AND THIRD DOSE OF THE SARS‐COV‐2 VACCINE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A PROSPECTIVE, CENTRALIZED, MULTICENTER STUDY.
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Mauro, F. R., Giannarelli, D., Galluzzo, C., Visentin, A., Frustaci, A. M., Sportoletti, P., Vitale, C., Reda, G., Gentile, M., Levato, L., Murru, R., Armiento, D., Ielo, C., Maglione, R., Crisanti, E., Cipiciani, A., Mattiello, V., Gianfelici, V., Barabino, L., and Amici, R.
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- 2022
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4. S139: BCOR DELETION SUSTAINS NOTCH1 SIGNALLING ACTIVATION TO ACCELERATE CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) PROGRESSION TOWARD RICHTER TRANSFORMATION IN MICE.
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Rompietti, C., Sorcini, D., De Falco, F., Dorillo, E., Adamo, F. M., Silva Barcelos, E. C., Stella, A., Scialdone, A., Esposito, A., Arcaleni, R., Bigerna, B., Martino, G., Moretti, L., Mameli, M. G., Geraci, C., Sandoletti, L., Cipiciani, A., Rosati, E., Falini, B., and Sportoletti, P.
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- 2022
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5. EFFICACY AND DISCONTINUATION RATE OF IBRUTINIB IN TREATMENT NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS WITH TP53 ABNORMALITIES. A REAL‐LIFE CAMPUS CLL STUDY.
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Visentin, A., Mauro, F. R., Cibien, F., Vitale, C., Reda, G., Fresa, A., Ciolli, S., Pietrasanta, D., Marchetti, M., Murru, R., Gentile, M., Rigolin, G. M., Quaglia, F. M., Scarfò, L., Sportoletti, P., Pravato, S., Romano Gargarella, L., Facco, M., Piazza, F., and Coscia, M.
- Published
- 2021
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6. TRACKING CLONAL HEMATOPOIESIS IN PATIENTS WITH CLASSICAL HODGKIN'S LYMPHOMA.
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Marra, A., Venanzi, A, Schiavoni, G., Milner, S. G., Limongello, R., Santi, A., Pettirossi, V., Ultimo, S., Tasselli, L., Pucciarini, A., Falini, L., Sciabolacci, S., Martelli, M. P., Sportoletti, P., Ascani, S., Falini, B., and Tiacci, E.
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- 2021
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7. The glucocorticoid-induced TNF receptor family-related protein (GITR) is critical to the development of acute pancreatitis in mice.
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Galuppo, M, Nocentini, G, Mazzon, E, Ronchetti, S, Esposito, E, Riccardi, L, Sportoletti, P, Di Paola, R, Bruscoli, S, Riccardi, C, and Cuzzocrea, S
- Subjects
PANCREATITIS ,GLUCOCORTICOIDS ,TUMOR necrosis factor receptors ,CERULEIN ,NITRIC-oxide synthases ,NF-kappa B ,LABORATORY mice ,PROTEIN metabolism ,T cells ,ANIMAL experimentation ,ANTIGENS ,APOPTOSIS ,CELL receptors ,COMPARATIVE studies ,EDEMA ,IMMUNITY ,INTERLEUKIN-1 ,LIGANDS (Biochemistry) ,RESEARCH methodology ,MEDICAL cooperation ,MICE ,OLIGOPEPTIDES ,OXIDOREDUCTASES ,RECOMBINANT proteins ,RESEARCH ,TRANSFERASES ,TUMOR necrosis factors ,EVALUATION research ,PREVENTION ,PHYSIOLOGY ,CELL physiology - Abstract
Background and Purpose: Pancreatitis represents a life-threatening inflammatory condition where leucocytes, cytokines and vascular endothelium contribute to the development of the inflammatory disease. The glucocorticoid-induced tumour necrosis factor (TNF) receptor family-related protein (GITR) is a costimulatory molecule for T lymphocytes, modulates innate and adaptive immune system and has been found to participate in a variety of immune responses and inflammatory processes. Our purpose was to verify whether inhibition of GITR triggering results in a better outcome in experimental pancreatitis.Experimental Approach: In male GITR knock-out (GITR(-/-)) and GITR(+/+) mice on Sv129 background, acute pancreatitis was induced after i.p. administration of cerulein. Other experimental groups of GITR(+/+) mice were also treated with different doses of Fc-GITR fusion protein (up to 6.25 µg·mouse⁻¹), given by implanted mini-osmotic pump. Clinical score and pro-inflammatory parameters were evaluated.Key Results: A less acute pancreatitis was found in GITR(-/-) mice than in GITR(+/+) mice, with marked differences in oedema, neutrophil infiltration, pancreatic dysfunction and injury. Co-treatment of GITR(+/+) mice with cerulein and Fc-GITR fusion protein (6.25 µg·mouse⁻¹) decreased the inflammatory response and tissue injury, compared with treatment with cerulein alone. Inhibition of GITR triggering was found to modulate activation of nuclear factor κB as well as the production of TNF-α, interleukin-1β, inducible nitric oxide synthase, nitrotyrosine, poly-ADP-ribose, intercellular adhesion molecule-1 and P-selectin.Conclusions and Implications: The GITR-GITR ligand system is crucial to the development of acute pancreatitis in mice. Our results also suggest that the Fc-GITR fusion protein could be useful in the treatment of acute pancreatitis. [ABSTRACT FROM AUTHOR]- Published
- 2011
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8. Choice of Frontline Tyrosine‐Kinase Inhibitor and Early Events in Very Elderly Patients With Chronic Myeloid Leukemia in Chronic Phase: A “Campus CML” Study.
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Bucelli, C., Capodanno, I., Miggiano, M. C., Cavazzini, F., Crescenzi, S. Leonetti, Russo, S., Carmosino, I., Annunziata, M., Sorà, F., Bonifacio, M., Luciano, L., Caocci, G., Loglisci, G., Elena, C., Lunghi, F., Mullai, R., Attolico, I., Binotto, G., Crisà, E., and Sportoletti, P.
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CHRONIC myeloid leukemia , *OLDER patients , *PROTEIN-tyrosine kinase inhibitors , *DASATINIB , *OLDER people - Abstract
ABSTRACT Objectives Methods Results Conclusions The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP‐CML patients.A retrospective analysis was conducted on 332 CP‐CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the “Campus CML” project.Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second‐generation TKIs (2G‐TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G‐TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra‐hematologic toxicity (9.5%), with no significant difference between IM and 2G‐TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G‐TKIs.IM was in our Centers the preferred frontline therapy for older CP‐CML patients, with increasing utilization after the introduction of generic formulations. However, 2G‐TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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9. Starry sky pattern predicts RAS pathway activation in NPM1-mutated acute myeloid leukemia.
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Venanzi A, Cardinali V, Perriello V, Albano F, Cimino G, Martino G, Marra A, Sportoletti P, Andresen V, Gjertsen BT, Sica S, Chiusolo P, Martelli MP, Tiacci E, and Falini B
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- 2024
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10. Venetoclax infectious risk score to identify patients with chronic lymphocytic leukemia at high infectious risk during venetoclax treatment: A multicenter SEIFEM study.
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Autore F, Visentin A, Deodato M, Vitale C, Galli E, Fresa A, Fazzi R, Sanna A, Olivieri J, Scortechini I, Del Principe MI, Sportoletti P, Schiattone L, Maschio N, Facchinelli D, Marchesi F, Coscia M, Tedeschi A, Trentin L, Innocenti I, Candoni A, Busca A, Pagano L, and Laurenti L
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- Humans, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Risk Factors, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Antineoplastic Agents therapeutic use, Sulfonamides
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- 2024
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11. Ibrutinib as first line therapy in chronic lymphocytic leukemia patients over 80 years old: A retrospective real-life multicenter Italian cohort.
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Martino EA, Mauro FR, Reda G, Laurenti L, Visentin A, Frustaci A, Vigna E, Pepe S, Catania G, Loseto G, Murru R, Chiarenza A, Sportoletti P, Del Principe MI, Laureana R, Coscia M, Galimberti S, Ferretti E, Zucchetto A, Bomben R, Polesel J, Tedeschi A, Rossi D, Trentin L, Neri A, Morabito F, Gattei V, and Gentile M
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- Aged, 80 and over, Humans, Italy, Retrospective Studies, Treatment Outcome, Adenine analogs & derivatives, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Piperidines
- Abstract
Although chronic lymphocytic leukemia (CLL) predominantly affects the elderly, limited data exists about the outcomes of over 80-year-old patients, usually underrepresented in clinical trials. We conducted a multicenter study enrolling 79 consecutive CLL patients ≥80 years at the time of frontline therapy, all treated with ibrutinib. Nearly 48% of cases exhibited unmutated IGHV genes, 32% 17p deletion, and 39.2% TP53 mutations; 63.3% displayed a cumulative illness rating scale (CIRS) > 6. The overall response rate on ibrutinib, computed in 74/79 patients (5 patients excluded for early withdrawal), was 89.9%. After a median follow-up of 28.9 months, the median progression-free survival (PFS) and overall survival (OS) were 42.5 and 51.8 months, respectively. CIRS>6 and temporary discontinuation of ibrutinib lasting for 7-30 days were the only parameters associated with a significantly shorter PFS and were both relevant in predicting a shorter PFS compared to patients with CIRS≤6 and therapy discontinuation ≤7 days. The most common grade≥3 adverse events were infections (25.5%), neutropenia (10.1%), and anemia (2.5%). Eighteen patients (22.8%) experienced a cardiovascular event, including grade-2 atrial fibrillation (n = 9; 11%), grade-2 hypertension (n = 5; 6%), heart failure (n = 3; 3%), and acute coronary syndrome (n = 1; 1%). Mild bleeding events were observed in 27 patients (34.2%). Ibrutinib was permanently discontinued in 26 patients due to progressive disease (n = 11, including 5 Richter's syndromes), secondary malignancies (n = 6), infections (n = 3), cardiac failure (n = 3), severe bleeding (n = 2), and sudden death (n = 1). In conclusion, our analyses confirmed the overall effectiveness and favorable safety profile of the ibrutinib-single agent therapeutic approach in CLL patients ≥80 years., (© 2024 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)
- Published
- 2024
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12. Patients' preferences for chronic lymphocytic leukemia treatment: The CHOICE study.
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Sportoletti P, Laurenti L, Chiarenza A, Gaidano G, Albi E, Mauro FR, Trentin L, Vallisa D, Pane F, Cuneo A, Albano F, Zamprogna G, Coscia M, Gozzetti A, Reda G, Caira M, Finsinger P, Gualberti G, Iannella E, Malgieri S, and Molica S
- Subjects
- Adult, Humans, Patient Preference, Quality of Life, Cross-Sectional Studies, Pandemics, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Abstract
Chronic lymphocytic leukemia (CLL) therapies differ in efficacy, side effects, route, frequency, and duration of administration. We assessed patient preferences for treatment attributes and evaluated associations with disease stage, treatment line, and socio-demographic characteristics in a cross sectional, observational study conducted at 16 Italian hematology centers. Study visits occurred between February and July 2020; 401 adult patients with CLL (201 Watch and Wait (W&W), 200 treated) participated in a discrete choice experiment (DCE), composed of 8 choices between pairs of treatment profiles with different levels of 5 attributes of currently available CLL treatments (length of response, route and duration of administration, risk of side effects including diarrhea, infections, or organ damage). Health-related quality of life was assessed with the EQ-5D-5L, EORTC QLQ-C30 and QLQ CLL-16. Previously treated patients had longer disease duration (7 vs. 5 years), higher prevalence of serious comorbidities (45.5% vs. 36.2%) and high-risk molecular markers (unmutated IGHV 55.6% vs. 17.1%; TP53 mutation 15.2% vs. 4.0%). Health-related quality of life scores were similar between groups. In the DCE, W&W patients rated "possible occurrence of infections" highest (relative importance [RI] = 36.2%), followed by "treatment and relevant duration" (RI = 28.0%) and "progression-free survival (PFS)" (RI = 16.9%). Previously treated patients rated "treatment and relevant duration" highest (RI = 33.3%), followed by "possible occurrence of infections" (RI = 28.8%), "possible occurrence of organ damage" (RI = 19.4%), and "PFS" (RI = 9.8%). Concern over infection was rated highest overall; unexpectedly PFS was not among the most important criteria in either group, suggesting that the first COVID-19 pandemic wave may have influenced patient preferences and concerns about CLL therapy options., (© 2023 Abbvie SRL and The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)
- Published
- 2024
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13. Lymphadenopathy as a predictor of progression during venetoclax treatment in chronic lymphocytic leukemia. A campus chronic lymphocytic leukemia study.
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Autore F, Innocenti I, Reda G, Visentin A, Vitale C, Piciocchi A, Fresa A, Leone MMA, Farina L, Quaresmini G, Baratè C, Giordano A, Ferrari A, Angeletti I, De Paolis MR, Malerba L, Chiurazzi F, Loseto G, Catania G, Sportoletti P, Scortechini I, Moia R, Gentile M, Rigolin GM, Mattiello V, Gattei V, Coscia M, Trentin L, Foà R, Cuneo A, and Laurenti L
- Subjects
- Humans, Retrospective Studies, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Recurrence, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Lymphadenopathy chemically induced, Lymphadenopathy drug therapy
- Abstract
Clinical or biological parameters useful to predict progression during treatment in real-life setting with ibrutinib, idelalisib and venetoclax in relapsed/refractory chronic lymphocytic leukemia (CLL) are still debated. We conducted a multi-center retrospective study on CLL patients treated with ibrutinib and/or idelalisib who were switched to venetoclax for progression or due to adverse events to identify any clinical and/or biological parameters useful to predict progression during treatment with venetoclax. Of all the 128 evaluable patients, 81 had received ibrutinib prior to switching to venetoclax, 35 had received idelalisib and 12 both. When comparing the three subgroups, we did not notice any statistical difference in terms of clinical or biological features. No variable at baseline and at different time points during the follow-up (at 6, 12, 18 and 24 months) was found to predict progression nor to have significance for Progression Free Survival (PFS) in the ibrutinib group and in the idelalisib group and in subgroups according to the line of treatment. Analyzing the data of the venetoclax treatment, after a median follow up of 14.3 months, median PFS was not reached and estimated 3-year PFS was 54%. Of the 128 patients treated with venetoclax, 28 (22%) experienced progressive disease. At multivariate analysis for predictive factors for progression, lymph node diameter >56.5 mm before starting treatment emerged as an independent risk factor for progression. The lymph node predictive role for progression during venetoclax treatment could be a new parameter that deserves to be investigate in future studies., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)
- Published
- 2023
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14. The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.
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Visentin A, Chatzikonstantinou T, Scarfò L, Kapetanakis A, Demosthenous C, Karakatsoulis G, Minga E, Chamou D, Allsup D, Cabrero AA, Andres M, Antic D, Baile M, Baliakas P, Besikli-Dimou S, Bron D, Chatzileontiadou S, Cordoba R, Correa JG, Cuéllar-García C, De Paoli L, De Paolis MR, Delgado J, Dimou M, Donaldson D, Catherwood M, Doubek M, Efstathopoulou M, Eichhorst B, Elashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Frederiksen H, Fürstenau M, García-Marco JA, García-Serra R, Collado R, Gentile M, Gimeno E, Glenthøj A, da Silva MG, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Innocenti I, Itchaki G, Jaksic O, Janssens A, Kalashnikova ОB, Kalicińska E, Kater AP, Kersting S, Labrador J, Lad D, Laurenti L, Levin MD, Lista E, Lopez-Garcia A, Malerba L, Marasca R, Marchetti M, Marquet J, Mattsson M, Mauro FR, Morawska M, Motta M, Munir T, Murru R, Niemann CU, Rodrigues RN, Olivieri J, Orsucci L, Papaioannou M, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Qvist K, Rigolin GM, Ruchlemer R, Šimkovič M, Špaček M, Sportoletti P, Stanca O, Tadmor T, Capasso A, Del Poeta G, Gutwein O, Karlsson LK, Milosevic I, Mirás F, Reda G, Saghumyan G, Shrestha A, Te Raa D, Tonino SH, Van Der Spek E, van Gelder M, van Kampen R, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Pocali B, Vandenberghe E, Iyengar S, Varettoni M, Vitale C, Coscia M, Rambaldi A, Montserrat E, Cuneo A, Stavroyianni N, Trentin L, Stamatopoulos K, and Ghia P
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- Humans, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Retrospective Studies, COVID-19, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
- Published
- 2023
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15. XPO1 mutations identify early-stage CLL characterized by shorter time to first treatment and enhanced BCR signalling.
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Moia R, Terzi di Bergamo L, Talotta D, Bomben R, Forestieri G, Spina V, Bruscaggin A, Cosentino C, Almasri M, Dondolin R, Bittolo T, Zucchetto A, Baldoni S, Del Giudice I, Mauro FR, Maffei R, Chiarenza A, Tafuri A, Laureana R, Del Principe MI, Zaja F, D'Arena G, Olivieri J, Rasi S, Mahmoud A, Al Essa W, Awikeh B, Kogila S, Bellia M, Mouhssine S, Sportoletti P, Marasca R, Scarfò L, Ghia P, Gattei V, Foà R, Rossi D, and Gaidano G
- Abstract
Here we evaluated the epigenomic and transcriptomic profile of XPO1 mutant chronic lymphocytic leukaemia (CLL) and their clinical phenotype. By ATAC-seq, chromatin regions that were more accessible in XPO1 mutated CLL were enriched of binding sites for transcription factors regulated by pathways emanating from the B-cell receptor (BCR), including NF-κB signalling, p38-JNK and RAS-RAF-MEK-ERK. XPO1 mutant CLL, consistent with the chromatin accessibility changes, were enriched with transcriptomic features associated with BCR and cytokine signalling. By combining epigenomic and transcriptomic data, MIR155HG, the host gene of miR-155, and MYB, the transcription factor that positively regulates MIR155HG, were upregulated by RNA-seq and their promoters were more accessible by ATAC-seq. To evaluate the clinical impact of XPO1 mutations, we investigated a total of 957 early-stage CLL subdivided into 3 independent cohorts (N = 276, N = 286 and N = 395). Next-generation sequencing analysis identified XPO1 mutations as a novel predictor of shorter time to first treatment (TTFT) in all cohorts. Notably, XPO1 mutations maintained their prognostic value independent of the immunoglobulin heavy chain variable status and early-stage prognostic models. These data suggest that XPO1 mutations, conceivably through increased miR-155 levels, may enhance BCR signalling leading to higher proliferation and shorter TTFT in early-stage CLL., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2023
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16. Continuous venetoclax in treatment-naive TP53 disrupted patients with chronic lymphocytic leukemia: A chronic lymphocytic leukemia campus study.
- Author
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Visentin A, Mauro FR, Scarfò L, Gentile M, Farina L, Reda G, Ferrarini I, Proietti G, Derenzini E, Cibien F, Vitale C, Sanna A, Pietrasanta D, Marchetti M, Murru R, Rigolin GM, Sportoletti P, Trimarco V, Cavarretta CA, Angotzi F, Cellini A, Ruocco V, Zatta I, Laurenti L, Molica S, Coscia M, Ghia P, Foà R, Cuneo A, and Trentin L
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- Humans, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Sulfonamides therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Tumor Suppressor Protein p53 genetics, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Antineoplastic Agents therapeutic use
- Published
- 2023
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17. Immune correlates of protection by vaccine against SARS-CoV-2 in patients with chronic lymphocytic leukaemia.
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Sorcini D, De Falco F, Gargaro M, Bozza S, Guarente V, Cardinali V, Stella A, Adamo FM, Silva Barcelos EC, Rompietti C, Dorillo E, Geraci C, Esposito A, Arcaleni R, Capoccia S, Mameli MG, Graziani A, Moretti L, Cipiciani A, Riccardi C, Mencacci A, Fallarino F, Rosati E, and Sportoletti P
- Subjects
- Humans, COVID-19 Vaccines therapeutic use, Tumor Necrosis Factor-alpha, SARS-CoV-2, Seroepidemiologic Studies, Interferon-gamma, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, COVID-19 prevention & control, Antineoplastic Agents therapeutic use, Vaccines
- Abstract
In chronic lymphocytic leukaemia (CLL) the efficacy of SARS-CoV-2 vaccination remains unclear as most studies have focused on humoral responses. Here we comprehensively examined humoral and cellular responses to vaccine in CLL patients. Seroconversion was observed in 55.2% of CLL with lower rate and antibody titres in treated patients. T-cell responses were detected in a significant fraction of patients. CD4
+ and CD8+ frequencies were significantly increased independent of serology with higher levels of CD4+ cells in patients under a Bruton tyrosine kinase (BTK) or a B-cell lymphoma 2 (BCL-2) inhibitor. Vaccination skewed CD8+ cells towards a highly cytotoxic phenotype, more pronounced in seroconverted patients. A high proportion of patients showed spike-specific CD4+ and CD8+ cells producing interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). Patients under a BTK inhibitor showed increased production of IFNγ and TNFα by CD4+ cells. Vaccination induced a Th1 polarization reverting the Th2 CLL T-cell profile in the majority of patients with lower IL-4 production in untreated and BTK-inhibitor-treated patients. Such robust T-cell responses may have contributed to remarkable protection against hospitalization and death in a cohort of 540 patients. Combining T-cell metrics with seroprevalence may yield a more accurate measure of population immunity in CLL, providing consequential insights for public health., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2023
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18. Efficacy of front-line ibrutinib versus fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: A retrospective multicenter "Real-World" study.
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Levi S, Bronstein Y, Goldschmidt N, Morabito F, Ziv-Baran T, Del Poeta G, Bairey O, Del Principe MI, Fineman R, Mauro FR, Gutwein O, Reda G, Ruchlemer R, Sportoletti P, Laurenti L, Shvidel L, Coscia M, Tadmor T, Varettoni M, Aviv A, Murru R, Braester A, Chiarenza A, Visentin A, Pietrasanta D, Loseto G, Zucchetto A, Bomben R, Olivieri J, Neri A, Rossi D, Gaidano G, Trentin L, Foà R, Cuneo A, Perry C, Gattei V, Gentile M, and Herishanu Y
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- Humans, Rituximab therapeutic use, Cyclophosphamide therapeutic use, Vidarabine therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Published
- 2023
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19. Use of BTK inhibitors with focus on ibrutinib in mantle cell lymphoma: An expert panel opinion statement.
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Zinzani PL, Martelli M, Ferrero S, Gentile M, Laurenti L, Romana Mauro F, Sportoletti P, Tedeschi A, Varettoni M, and Visco C
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- Adenine analogs & derivatives, Adult, Agammaglobulinaemia Tyrosine Kinase antagonists & inhibitors, Humans, Piperidines, Antineoplastic Agents therapeutic use, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell pathology, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use
- Abstract
The introduction of Bruton's tyrosine kinase (BTK) inhibitors transformed the management of patients with mantle cell lymphoma (MCL). Ibrutinib, the first-in-class BTK inhibitor is now approved in more than 80 countries and there are over 20 new BTK inhibitors in development. In addition, novel agents show potential clinical activity (alone and in combination) and are in the approval phase and/or being studied in ongoing clinical trials. How does the practicing clinician decide on the optimal therapeutic strategy for this highly heterogenous disease? In July 2020 a group of experts from Italy, convened a meeting to address and provide clarification on a series of outstanding issues in the treatment of MCL with the view of providing clinical guidance on its management. This expert opinion statement represents the panel's collective analysis, evaluation, and recommendations and is made up of a series of questions and answers (in the form of a review of the pertinent literature) designed to replicate those posed by practicing clinicians in Italy but which are applicable to clinical settings worldwide., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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20. Use of BTK inhibitors with special focus on ibrutinib in Waldenström macroglobulinemia: An expert panel opinion statement.
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Ferrero S, Gentile M, Laurenti L, Mauro FR, Martelli M, Sportoletti P, Visco C, Zinzani PL, Tedeschi A, and Varettoni M
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- Adenine analogs & derivatives, Agammaglobulinaemia Tyrosine Kinase, Humans, Piperidines, Protein Kinase Inhibitors adverse effects, Pyrazoles adverse effects, Pyrimidines pharmacology, Pyrimidines therapeutic use, Waldenstrom Macroglobulinemia drug therapy
- Abstract
The pivotal role that ibrutinib plays in the management of Waldenström macroglobulinemia (WM) is undisputed but there are ongoing questions regarding its positioning in the therapeutic algorithm of WM as well as in some peculiar clinical situations. A panel of experts from Italy was convened to provide real world recommendations on the use of BTK inhibitors in lymphoproliferative diseases in general, and in patients with WM in particular. This position paper represents the panel's collective analysis, evaluation, and opinions and is made up of a series of questions frequently asked by practicing clinicians and answers based on currently available evidence., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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21. Prediction of outcomes in chronic lymphocytic leukemia patients treated with ibrutinib: Validation of current prognostic models and development of a simplified three-factor model.
- Author
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Molica S, Giannarelli D, Visentin A, Reda G, Sportoletti P, Frustaci AM, Chiarenza A, Ciolli S, Vitale C, Laurenti L, De Paoli L, Murru R, Gentile M, Moia R, Rigolin GM, Levato L, Giordano A, Del Poeta G, Stelitano C, Deodato M, Ielo C, Noto A, Guarente V, Coscia M, Tedeschi A, Gaidano G, Cuneo A, Foa' R, Trentin L, and Mauro FR
- Subjects
- Adenine analogs & derivatives, Humans, Piperidines, Prognosis, Protein Kinase Inhibitors adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Published
- 2022
- Full Text
- View/download PDF
22. Continuous treatment with Ibrutinib in 100 untreated patients with TP53 disrupted chronic lymphocytic leukemia: A real-life campus CLL study.
- Author
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Visentin A, Mauro FR, Cibien F, Vitale C, Reda G, Fresa A, Ciolli S, Pietrasanta D, Marchetti M, Murru R, Gentile M, Rigolin GM, Quaglia FM, Scarfò L, Sportoletti P, Pravato S, Piazza F, Coscia M, Laurenti L, Molica S, Foà R, Cuneo A, and Trentin L
- Subjects
- Adenine administration & dosage, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Adenine analogs & derivatives, Gene Deletion, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Piperidines administration & dosage, Tumor Suppressor Protein p53 genetics
- Published
- 2022
- Full Text
- View/download PDF
23. COVID-19 infection in chronic myeloid leukaemia after one year of the pandemic in Italy. A Campus CML report.
- Author
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Breccia M, Abruzzese E, Accurso V, Attolico I, Barulli S, Bergamaschi M, Binotto G, Bocchia M, Bonifacio M, Caocci G, Capodanno I, Castagnetti F, Cavazzini F, Crisà E, Crugnola M, Stella De Candia M, Elena C, Fava C, Galimberti S, Gozzini A, Gugliotta G, Intermesoli T, Iurlo A, La Barba G, Latagliata R, Leonetti Crescenzi S, Levato L, Loglisci G, Lucchesi A, Luciano L, Lunghi F, Luzi D, Malato A, Cristina Miggiano M, Pizzuti M, Pregno P, Rapezzi D, Rege-Cambrin G, Rosti G, Russo S, Sancetta R, Rita Scortechini A, Sorà F, Sportoletti P, Stagno F, Tafuri A, Tiribelli M, Foà R, and Saglio G
- Subjects
- Aged, Disease-Free Survival, Female, Humans, Italy epidemiology, Male, Middle Aged, Retrospective Studies, Survival Rate, COVID-19 diagnosis, COVID-19 mortality, COVID-19 therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Pandemics, SARS-CoV-2
- Abstract
Limited information is available on the impact of the COVID-19 pandemic on the management of chronic myeloid leukaemia (CML). The Campus CML network collected retrospective information on 8 665 CML patients followed at 46 centres throughout Italy during the pandemic between February 2020 and January 2021. Within this cohort, we recorded 217 SARS-CoV-2-positive patients (2·5%). Most patients (57%) were diagnosed as having SARS-CoV-2 infection during the second peak of the pandemic (September 2020 to January 2021). The majority (35%) was aged between 50 and 65 years with a male prevalence (73%). Fifty-six percent of patients presented concomitant comorbidities. The median time from CML diagnosis to SARS-CoV-2 infection was six years (three months to 18 years). Twenty-one patients (9·6%) required hospitalization without the need of respiratory assistance, 18 (8·2%) were hospitalized for respiratory assistance, 8 (3·6%) were admitted to an intensive care unit, while 170 (78%) were only quarantined. Twenty-three percent of patients discontinued tyrosine kinase inhibitor (TKI) therapy during the infection. Twelve patients died due to COVID-19 with a mortality rate of 5·5% in the positive cohort and of 0·13% in the whole cohort. We could also document sequelae caused by the SARS-CoV-2 infection and an impact of the pandemic on the overall management of CML patients., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
24. Management of chronic lymphocytic leukemia in Italy during a one year of the COVID-19 pandemic and at the start of the vaccination program. A Campus CLL report.
- Author
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Cuneo A, Rigolin GM, Coscia M, Quaresmini G, Scarfò L, Mauro FR, Motta M, Quaglia FM, Trentin L, Ferrario A, Laurenti L, Reda G, Ferrari A, Pietrasanta D, Sportoletti P, Re F, De Paoli L, Foglietta M, Giordano A, Marchetti M, Farina L, Del Poeta G, Varettoni M, Chiurazzi F, Marasca R, Malerba L, Ibatici A, Tisi MC, Stefoni V, Leone M, Baratè C, Olivieri J, Murru R, Gentile M, Sanna A, Gozzetti A, Gattei V, Gottardi D, Derenzini E, Levato L, Orsucci L, Penna G, Chiarenza A, and Foà R
- Subjects
- Aged, COVID-19 prevention & control, COVID-19 transmission, COVID-19 virology, Disease Management, Female, Humans, Italy epidemiology, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology, Leukemia, Lymphocytic, Chronic, B-Cell virology, Male, Middle Aged, Prognosis, Time Factors, COVID-19 complications, Leukemia, Lymphocytic, Chronic, B-Cell therapy, SARS-CoV-2 immunology, Vaccination methods
- Published
- 2021
- Full Text
- View/download PDF
25. TP53 disruption as a risk factor in the era of targeted therapies: A multicenter retrospective study of 525 chronic lymphocytic leukemia cases.
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Morabito F, Del Poeta G, Mauro FR, Reda G, Sportoletti P, Laurenti L, Coscia M, Herishanu Y, Bossio S, Varettoni M, Murru R, Chiarenza A, Visentin A, Condoluci A, Moia R, Pietrasanta D, Loseto G, Consoli U, Scortechini I, Recchia AG, Rossi FM, Zucchetto A, Al-Janazreh H, Martino EA, Vigna E, Tripepi G, D'Arrigo G, Galimberti S, Rago A, Angeletti I, Biagi A, Del Giudice I, Bomben R, Neri A, Fronza G, Cutrona G, Jaksic O, Olivieri J, Rossi D, Di Raimondo F, Cuneo A, Gaidano G, Polliack A, Trentin L, Foà R, Ferrarini M, Gattei V, and Gentile M
- Subjects
- Chromosome Deletion, Chromosomes, Human, Pair 17, Humans, Molecular Targeted Therapy, Mutation, Prognosis, Retrospective Studies, Risk Factors, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Tumor Suppressor Protein p53 genetics
- Published
- 2021
- Full Text
- View/download PDF
26. Efficacy of idelalisib and rituximab in relapsed/refractory chronic lymphocytic leukemia treated outside of clinical trials. A report of the Gimema Working Group.
- Author
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Rigolin GM, Cavazzini F, Piciocchi A, Arena V, Visentin A, Reda G, Zamprogna G, Cibien F, Vitagliano O, Coscia M, Farina L, Gaidano G, Murru R, Varettoni M, Paolini R, Sportoletti P, Pietrasanta D, Molinari AL, Quaglia FM, Laurenti L, Marasca R, Marchetti M, Mauro FR, Crea E, Vignetti M, Gentile M, Montillo M, Foà R, and Cuneo A
- Subjects
- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Disease-Free Survival, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Middle Aged, Purines administration & dosage, Purines adverse effects, Quinazolinones administration & dosage, Quinazolinones adverse effects, Recurrence, Rituximab administration & dosage, Rituximab adverse effects, Survival Rate, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality
- Abstract
Because the efficacy of new drugs reported in trials may not translate into similar results when used in the real-life, we analyzed the efficacy of idelalisib and rituximab (IR) in 149 patients with relapsed/refractory chronic lymphocytic leukemia treated at 34 GIMEMA centers. Median progression-free survival (PFS) and overall survival were 22.9 and 44.5 months, respectively; performance status (PS) ≥2 and ≥3 previous lines of therapy were associated with shorter PFS and overall survival (OS). 48% of patients were on treatment at 12 months; the experience of the centers (≥5 treated patients) and PS 0-1 were associated with a significantly longer treatment duration (p = 0.015 and p = 0.002, respectively). TP53 disruption had no prognostic significance. The overall response rate to subsequent treatment was 49.2%, with median OS of 15.5 months and not reached in patients who discontinued, respectively, for progression and for toxicity (p < 0.01). Treatment breaks ≥14 days were recorded in 96% of patients and adverse events mirrored those reported in trials. In conclusion, this real-life analysis showed that IR treatment duration was longer at experienced centers, that the ECOG PS and ≥3 lines of previous therapy are strong prognostic factor and that the overall outcome with this regimen was superimposable to that reported in a randomized trial., (© 2021 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
27. Effectiveness of ibrutinib as first-line therapy for chronic lymphocytic leukemia patients and indirect comparison with rituximab-bendamustine: Results of study on 486 cases outside clinical trials.
- Author
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Morabito F, Tripepi G, Del Poeta G, Mauro FR, Reda G, Sportoletti P, Laurenti L, Coscia M, Herishanu Y, Bossio S, Varettoni M, Murru R, Chiarenza A, Visentin A, Condoluci A, Moia R, Pietrasanta D, Loseto G, Consoli U, Scortechini I, Rossi FM, Zucchetto A, Al-Janazreh H, Vigna E, Martino EA, Cassin R, D Arrigo G, Galimberti S, Rago A, Angeletti I, Biagi A, Del Giudice I, Bomben R, Neri A, Fronza G, Monti P, Menichini P, Olivieri J, Cutrona G, Rossi D, Cuneo A, Di Raimondo F, Gaidano G, Polliack A, Trentin L, Foà R, Ferrarini M, Gattei V, and Gentile M
- Subjects
- Adenine pharmacology, Adenine therapeutic use, Aged, Bendamustine Hydrochloride pharmacology, Humans, Piperidines pharmacology, Progression-Free Survival, Rituximab pharmacology, Adenine analogs & derivatives, Bendamustine Hydrochloride therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Piperidines therapeutic use, Rituximab therapeutic use
- Published
- 2021
- Full Text
- View/download PDF
28. Assessment of the 4-factor score: Retrospective analysis of 586 CLL patients receiving ibrutinib. A campus CLL study.
- Author
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Morabito F, Tripepi G, Del Poeta G, Mauro FR, Reda G, Sportoletti P, Laurenti L, Coscia M, Herishanu Y, Varettoni M, Murru R, Chiarenza A, Visentin A, Condoluci A, Moia R, Pietrasanta D, Loseto G, Consoli U, Scortechini I, Rossi FM, Zucchetto A, Vigna E, Martino EA, Mendicino F, Botta C, Caracciolo D, Cassin R, D'Arrigo G, Galimberti S, Rago A, Angeletti I, Biagi A, Del Giudice I, Bomben R, Neri A, Fronza G, Cutrona G, Rossi D, Di Raimondo F, Cuneo A, Gaidano G, Polliack A, Trentin L, Foà R, Ferrarini M, Gattei V, and Gentile M
- Subjects
- Adenine therapeutic use, Aged, Datasets as Topic statistics & numerical data, Female, Follow-Up Studies, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Multicenter Studies as Topic, Prognosis, Progression-Free Survival, Proportional Hazards Models, Reproducibility of Results, Retrospective Studies, Risk Assessment, Survival Analysis, Adenine analogs & derivatives, Antineoplastic Agents therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Piperidines therapeutic use, Protein Kinase Inhibitors therapeutic use, Severity of Illness Index
- Published
- 2021
- Full Text
- View/download PDF
29. Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group.
- Author
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Herishanu Y, Shaulov A, Fineman R, Bašić-Kinda S, Aviv A, Wasik-Szczepanek E, Jaksic O, Zdrenghea M, Greenbaum U, Mandac I, Simkovic M, Morawska M, Benjamini O, Spacek M, Nemets A, Bairey O, Trentin L, Ruchlemer R, Laurenti L, Stanca Ciocan O, Doubek M, Shvidel L, Dali N, Mirás F, De Meûter A, Dimou M, Mauro FR, Coscia M, Bumbea H, Szász R, Tadmor T, Gutwein O, Gentile M, Scarfò L, Tedeschi A, Sportoletti P, Gimeno Vázquez E, Marquet J, Assouline S, Papaioannou M, Braester A, Levato L, Gregor M, Rigolin GM, Loscertales J, Medina Perez A, Nijziel MR, Popov VM, Collado R, Slavutsky I, Itchaki G, Ringelstein S, Goldschmidt N, Perry C, Levi S, Polliack A, and Ghia P
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chlorambucil administration & dosage, Chlorambucil adverse effects, Disease-Free Survival, Female, Humans, Male, Retrospective Studies, Survival Rate, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Chromosome Deletion, Chromosomes, Human, Pair 17 genetics, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Tumor Suppressor Protein p53 genetics
- Abstract
In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease., (© 2020 Wiley Periodicals, Inc.)
- Published
- 2020
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30. Venetoclax in CLL patients who progress after B-cell Receptor inhibitor treatment: a retrospective multi-centre Italian experience.
- Author
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Innocenti I, Morelli F, Autore F, Piciocchi A, Frustaci A, Mauro FR, Schiattone L, Trentin L, Del Poeta G, Reda G, Rigolin GM, Ibatici A, Ciolli S, Coscia M, Sportoletti P, Murru R, Levato L, Gentile M, D'Arena G, Efremov DG, Tedeschi A, Scarfò L, Cuneo A, Foà R, and Laurenti L
- Subjects
- Adenine analogs & derivatives, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Disease Progression, Drug Administration Schedule, Humans, Kaplan-Meier Estimate, Piperidines, Purines administration & dosage, Pyrazoles administration & dosage, Pyrimidines administration & dosage, Quinazolinones administration & dosage, Receptors, Antigen, B-Cell antagonists & inhibitors, Retrospective Studies, Sulfonamides administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Published
- 2019
- Full Text
- View/download PDF
31. Perspectives for therapeutic targeting of gene mutations in acute myeloid leukaemia with normal cytogenetics.
- Author
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Falini B, Sportoletti P, Brunetti L, and Martelli MP
- Subjects
- Animals, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors, DNA (Cytosine-5-)-Methyltransferases genetics, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methyltransferase 3A, DNA-Binding Proteins antagonists & inhibitors, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Dioxygenases, Epigenesis, Genetic drug effects, Epigenesis, Genetic genetics, Gene Expression Regulation, Leukemic drug effects, Gene Expression Regulation, Leukemic genetics, Humans, Interleukin-3 Receptor alpha Subunit biosynthesis, Interleukin-3 Receptor alpha Subunit genetics, Isocitrate Dehydrogenase antagonists & inhibitors, Isocitrate Dehydrogenase genetics, Isocitrate Dehydrogenase metabolism, Leukemia, Myeloid, Acute metabolism, Mutation, Nuclear Proteins antagonists & inhibitors, Nuclear Proteins genetics, Nuclear Proteins metabolism, Nucleophosmin, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Sialic Acid Binding Ig-like Lectin 3 biosynthesis, Sialic Acid Binding Ig-like Lectin 3 genetics, Transcription, Genetic drug effects, Transcription, Genetic genetics, fms-Like Tyrosine Kinase 3 antagonists & inhibitors, fms-Like Tyrosine Kinase 3 genetics, fms-Like Tyrosine Kinase 3 metabolism, Antineoplastic Agents therapeutic use, Drug Delivery Systems methods, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
The acute myeloid leukaemia (AML) genome contains more than 20 driver recurrent mutations. Here, we review the potential for therapeutic targeting of the most common mutations associated with normal cytogenetics AML, focusing on those affecting the FLT3, NPM1 and epigenetic modifier genes (DNMT3A, IDH1/2, TET2). As compared to early compounds, second generation FLT3 inhibitors are more specific and have better pharmacokinetics. They also show higher anti-leukaemic activity, leading to about 50% of composite complete remissions in refractory/relapsed FLT3-internal tandem duplication-mutated AML. However, rapid relapses invariably occur due to various mechanisms of resistance to FLT3 inhibitors. This issue and the best way for using FLT3 inhibitors in combination with other therapeutic modalities are discussed. Potential approaches for therapeutic targeting of NPM1-mutated AML include: (i) reverting the aberrant nuclear export of NPM1 mutant using exportin-1 inhibitors; (ii) disruption of the nucleolus with drugs blocking the oligomerization of wild-type nucleophosmin or inducing nucleolar stress; and (iii) immunotherapeutic targeting of highly expressed CD33 and IL3RA (CD123) antigens. Finally, we discuss the role of demethylating agents (decitabine and azacitidine) and IDH1/2 inhibitors in the treatment of AML patients carrying mutations of genes (DNMT3A, IDH1/2 and TET2) involved in the epigenetic regulation of transcription., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
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32. NOTCH1 PEST domain mutation is an adverse prognostic factor in B-CLL.
- Author
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Sportoletti P, Baldoni S, Cavalli L, Del Papa B, Bonifacio E, Ciurnelli R, Bell AS, Di Tommaso A, Rosati E, Crescenzi B, Mecucci C, Screpanti I, Marconi P, Martelli MF, Di Ianni M, and Falzetti F
- Subjects
- Humans, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation, Receptor, Notch1 genetics
- Published
- 2010
- Full Text
- View/download PDF
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