39 results on '"Alessia Tieghi"'
Search Results
2. P505: GIMEMA AML1819 TRIAL: GEMTUZUMAB OZOGAMICIN PLUS INTENSIVE CHEMOTHERAPY IMPACTS ON THE LEVEL OF POST-CONSOLIDATION MEASURABLE RESIDUAL DISEASE (MRD) IN ACUTE MYELOID LEUKEMIA
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Adriano Venditti, Alfonso Piciocchi, Luca Maurillo, Maria Ilaria Del Principe, Raffaele Palmieri, Stefano Soddu, Federico Moretti, Prassede Salutari, Maurizio Martelli, Maria Paola Martelli, Mario Luppi, Alessandro Pulsoni, Francesco Zaja, Roberto Cairoli, Fabrizio Pane, Sergio Siragusa, Renato Bassan, Michela Rondoni, Milena Mirabile, Antonino Mulè, Germana Beltrami, Patrizia Zappasodi, Laura Cudillo, Andrea Mengarelli, Antonio Curti, Felicetto Ferrara, Giovanni Rossi, Ernesta Audisio, Giuseppina Spinosa, Alessia Tieghi, Monica Bocchia, Vincenza Martini, Catello Califano, Luigi Rigacci, Agostino Tafuri, Michele Gottardi, Paola Fazi, Marco Vignetti, and Francesco Buccisano
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. P1028: MYELOFIBROSIS (MF) TREATED WITH RUXOLITINIB (RUX) MONOTHERAPY: PREDICTORS OF EARLY DISCONTINUATION AND DEATH ON TREATMENT. THE SHORT-TERM RUX PROGNOSTIC MODEL (STR-PM)
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Francesca Palandri, Giuseppe Auteri, Alessandra Iurlo, Elena Maria Elli, Simona Paglia, Massimiliano Bonifacio, Mario Tiribelli, Malgorzata Monica Trawinska, Nicola Polverelli, Giulia Benevolo, Alessia Tieghi, Florian Heidel, Fabrizio Cavalca, Giovanni Caocci, Eloise Beggiato, Gianni Binotto, Francesco Cavazzini, Maurizio Miglino, Costanza Bosi, Monica Crugnola, Monica Bocchia, Bruno Martino, Novella Pugliese, Marta Venturi, Camilla Mazzoni, Alessandro Isidori, Daniele Cattaneo, Mauro Krampera, Fabrizio Pane, Daniela Cilloni, Gianpietro Semenzato, Roberto M. Lemoni, Antonio Cuneo, Elisabetta Abruzzese, Nicola Vianelli, Michele Cavo, Giuseppe Palumbo, and Massimo Breccia
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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4. Incidence, mortality, and survival of hematological malignancies in Northern Italian patients: an update to 2020
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Lucia Mangone, Domenico Penna, Francesco Marinelli, Francesca Roncaglia, Isabella Bisceglia, Francesco Merli, Alessia Ruffini, Barbara Gamberi, Alessia Tieghi, Riccardo Valli, Laura Albertazzi, Mauro Iori, Paolo Giorgi Rossi, Claudia Vener, Fortunato Morabito, Antonino Neri, and Stefano Luminari
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hematological malignancies ,incidence ,mortality ,survival ,trends ,cancer registry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundHematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs’ accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis.Material and methodsA dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs’ main categories, were noted.ResultsOverall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records.ConclusionsThe study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency.
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- 2023
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5. A Prognostic Model to Predict Ruxolitinib Discontinuation and Death in Patients with Myelofibrosis
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Francesca Palandri, Giuseppe A. Palumbo, Massimiliano Bonifacio, Elena M. Elli, Mario Tiribelli, Giuseppe Auteri, Malgorzata M. Trawinska, Nicola Polverelli, Giulia Benevolo, Alessia Tieghi, Fabrizio Cavalca, Giovanni Caocci, Eloise Beggiato, Gianni Binotto, Francesco Cavazzini, Maurizio Miglino, Costanza Bosi, Monica Crugnola, Monica Bocchia, Bruno Martino, Novella Pugliese, Marta Venturi, Alessandro Isidori, Daniele Cattaneo, Mauro Krampera, Fabrizio Pane, Daniela Cilloni, Gianpietro Semenzato, Roberto M. Lemoli, Antonio Cuneo, Elisabetta Abruzzese, Filippo Branzanti, Nicola Vianelli, Michele Cavo, Florian Heidel, Alessandra Iurlo, and Massimo Breccia
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ruxolitinib ,myelofibrosis ,prognostic model ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Most patients with myelofibrosis (MF) discontinue ruxolitinib (JAK1/JAK2 inhibitor) in the first 5 years of therapy due to therapy failure. As the therapeutic possibilities of MF are expanding, it is critical to identify patients predisposed to early ruxolitinib monotherapy failure and worse outcomes. We investigated predictors of early ruxolitinib discontinuation and death on therapy in 889 patients included in the “RUX-MF” retrospective study. Overall, 172 patients were alive on ruxolitinib after ≥5 years (long-term ruxolitinib, LTR), 115 patients were alive but off ruxolitinib after ≥5 yrs (short-term RUX, STR), and 123 patients died while on ruxolitinib after p = 0.08). Overall survival (OS) was significantly longer in LTR pts (p = 0.002). In multivariate analysis, PLT < 100 × 109/L, Hb < 10 g/dL, primary MF, absence of spleen response at 3 months and ruxolitinib starting dose
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- 2023
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6. Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study
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Francesca Palandri, Elena Rossi, Giuseppe Auteri, Massimo Breccia, Simona Paglia, Giulia Benevolo, Elena M. Elli, Francesco Cavazzini, Gianni Binotto, Alessia Tieghi, Mario Tiribelli, Florian H. Heidel, Massimiliano Bonifacio, Novella Pugliese, Giovanni Caocci, Monica Crugnola, Francesco Mendicino, Alessandra D'Addio, Simona Tomassetti, Bruno Martino, Nicola Polverelli, Sara Ceglie, Camilla Mazzoni, Rikard Mullai, Alessia Ripamonti, Bruno Garibaldi, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Giuseppe A. Palumbo, Alessandro Andriani, Michele Cavo, Roberto Latagliata, and Valerio De Stefano
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myeloproliferative neoplasms ,polycythemia vera ,hydroxyurea ,ruxolitinib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.
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- 2023
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7. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis
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Francesca Palandri, Giuseppe Alberto Palumbo, Elena Maria Elli, Nicola Polverelli, Giulia Benevolo, Bruno Martino, Elisabetta Abruzzese, Mario Tiribelli, Alessia Tieghi, Roberto Latagliata, Francesco Cavazzini, Micaela Bergamaschi, Gianni Binotto, Monica Crugnola, Alessandro Isidori, Giovanni Caocci, Florian Heidel, Novella Pugliese, Costanza Bosi, Daniela Bartoletti, Giuseppe Auteri, Daniele Cattaneo, Luigi Scaffidi, Malgorzata Monica Trawinska, Rossella Stella, Fiorella Ciantia, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto Massimo Lemoli, Alessandra Iurlo, Nicola Vianelli, Michele Cavo, Massimo Breccia, and Massimiliano Bonifacio
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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8. Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments
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Valerio De Stefano, Tommaso Za, Elena Rossi, Alessandro M. Vannucchi, Marco Ruggeri, Elena Elli, Caterina Micò, Alessia Tieghi, Rossella R. Cacciola, Cristina Santoro, Giancarla Gerli, Nicola Vianelli, Paola Guglielmelli, Lisa Pieri, Francesca Scognamiglio, Francesco Rodeghiero, Enrico M. Pogliani, Guido Finazzi, Luigi Gugliotta, Roberto Marchioli, Giuseppe Leone, and Tiziano Barbui
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background Prior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal strategy for prevention of recurrence.Design and Methods We retrospectively estimated the rate of recurrence in a multicenter cohort of 494 patients (poly-cythemia vera/essential thrombocythemia 235/259) with previous arterial (67.6%) or venous thrombosis (31%) or both (1.4%). First thrombosis was cerebrovascular disease in 191 cases, acute coronary syndrome in 106, peripheral arterial thrombosis in 44, and venous thromboembolism in 160. Microcirculatory events were not computed.Results Thrombosis recurred in 166 patients (33.6%), with an incidence of 7.6% patient-years. Sex, diagnosis (polycythemia vera or essential thrombocythemia), and presence of vascular risk factors did not predict recurrence, whereas age >60 years did (multivariable hazard ratio [HR], 1.67; 95% confidence interval [CI] 1.19–2.32). Increased leukocyte count at the time of the first thrombosis was a risk factor for recurrence in patients
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- 2008
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9. Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors
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F. Efficace, David Cella, Roberto Cairoli, Agostino Tafuri, Francesco Cottone, Silvia Maria Trisolini, Laura B. Oswald, Antonio Cuneo, Maria Paola Martelli, Lorella Melillo, Anna Candoni, Marco Vignetti, Adriano Venditti, Francesco Albano, Alessia Tieghi, Mario Luppi, Prassede Salutari, Paola Fazi, Gabriella Storti, Oswald, L, Venditti, A, Cella, D, Cottone, F, Candoni, A, Melillo, L, Cairoli, R, Storti, G, Salutari, P, Luppi, M, Albano, F, Martelli, M, Cuneo, A, Tafuri, A, Trisolini, S, Tieghi, A, Fazi, P, Vignetti, M, and Efficace, E
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medicine.medical_specialty ,fatigue ,leukaemia ,quality of life ,supportive care ,symptoms and symptom management ,Population ,Population comparison ,Psychological intervention ,Medicine (miscellaneous) ,Newly diagnosed ,NO ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Medicine ,Clinical significance ,education ,education.field_of_study ,Oncology (nursing) ,business.industry ,General Medicine ,Settore MED/15 ,Clinical trial ,Medical–Surgical Nursing ,030220 oncology & carcinogenesis ,Myeloid leukaemia ,business ,030215 immunology - Abstract
ObjectivesThis study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity.MethodsPretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML.ResultsPatients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI −8.6 to −6.4, pConclusionsPatients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue.
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- 2021
10. Risk factors for progression to blast phase and outcome in 589 patients with myelofibrosis treated with ruxolitinib: Real-world data
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Massimo Breccia, Mauro Krampera, Alessandro Isidori, Monica Crugnola, Daniela Bartoletti, Elena Maria Elli, Alessia Tieghi, Massimiliano Bonifacio, Micaela Bergamaschi, Costanza Bosi, Roberto Latagliata, Roberto M. Lemoli, Francesco Cavazzini, Florian H. Heidel, Michele Cavo, Nicola Polverelli, Malgorzata Monika Trawinska, Francesca Palandri, Bruno Martino, Daniele Cattaneo, Giulia Benevolo, Giuseppe Auteri, Elisabetta Abruzzese, Gianni Binotto, Alessandra Iurlo, Nicola Vianelli, Antonio Cuneo, Francesco Di Raimondo, Dorian Forte, Davide Griguolo, Gianpietro Semenzato, Giuseppe A. Palumbo, Mario Tiribelli, Palandri F., Breccia M., Tiribelli M., Bonifacio M., Benevolo G., Iurlo A., Elli E.M., Binotto G., Tieghi A., Polverelli N., Martino B., Abruzzese E., Bergamaschi M., Heidel F.H., Cavazzini F., Crugnola M., Bosi C., Isidori A., Auteri G., Forte D., Latagliata R., Griguolo D., Cattaneo D., Trawinska M., Bartoletti D., Krampera M., Semenzato G., Lemoli R.M., Cuneo A., Di Raimondo F., Vianelli N., Cavo M., and Palumbo G.A.
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Male ,Cancer Research ,Ruxolitinib ,ruxolitinib ,Gastroenterology ,0302 clinical medicine ,myelofibrosi ,80 and over ,risk factors ,blast phase ,myelofibrosis ,outcome ,Adult ,Aged ,Aged, 80 and over ,Blast Crisis ,Disease Progression ,Female ,Follow-Up Studies ,Humans ,Janus Kinases ,Middle Aged ,Primary Myelofibrosis ,Prognosis ,Pyrazoles ,Retrospective Studies ,Survival Rate ,Young Adult ,Incidence (epidemiology) ,Hematology ,General Medicine ,risk factor ,Oncology ,030220 oncology & carcinogenesis ,blast phase, myelofibrosis, outcome, risk factors, ruxolitinib, Blast Crisis, Disease Progression ,medicine.drug ,medicine.medical_specialty ,Socio-culturale ,Alpha interferon ,03 medical and health sciences ,Internal medicine ,Nitriles ,medicine ,Risk factor ,Myelofibrosis ,Survival rate ,business.industry ,Induction chemotherapy ,Anagrelide ,medicine.disease ,Pyrimidines ,business ,030215 immunology - Abstract
The impact of ruxolitinib therapy on evolution to blast phase (BP) in patients with myelofibrosis (MF) is still uncertain. In 589 MF patients treated with ruxolitinib, we investigated incidence and risk factors for BP and we described outcome according to disease characteristics and treatment strategy. After a median follow-up from ruxolitinib start of 3 years (range 0.1-7.6), 65 (11%) patients transformed to BP during (93.8%) or after treatment. BP incidence rate was 3.7 per 100 patient-years, comparably in primary and secondary MF (PMF/SMF) but significantly lower in intermediate-1 risk patients (2.3 vs 5.6 per 100 patient-years in intermediate-2/high-risk patients, P
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- 2020
11. Arterial thrombosis in myeloproliferative neoplasms predict second cancer. Clinical observations in a case-control study
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Valerio De Stefano, Arianna, Ghirardi, Arianna, Masciulli, Alessandra, Carobbio, Francesca, Palandri, Nicola, Vianelli, Elena, Rossi, Silvia, Betti, Ambra Di Veroli, Alessandra, Iurlo, Daniele, Cattaneo, Guido, Finazzi, Massimiliano, Bonifacio, Luigi, Scaffidi, Andrea, Patriarca, Elisa, Rumi, Ilaria Carola Casetti, Clemency, Stephenson, Paola, Guglielmelli, Elena Maria Elli, Miroslava, Palova, Davide, Rapezzi, Daniel, Erez, Montse, Gomez, Kai, Wille, Manuel, Perez-Encinas, Francesca, Lunghi, Anna, Angona, Maria Laura Fox, Eloise, Beggiato, Giulia, Benevolo, Giuseppe, Carli, Cacciola, Rossella Rosaria, Mary Frances McMullin, Alessia, Tieghi, Valle, Recasens, Monia, Marchetti, Martin, Griesshammer, Alberto, Alvarez-Larràn, Alessandro Maria Vannucchi, Alessandro, Rambaldi, and Tiziano, Barbui
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- 2020
12. Second primary malignancy in myelofibrosis patients treated with ruxolitinib
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Elena Maria Elli, Florian H. Heidel, Uros Markovic, Fabrizio Pane, Gianpietro Semenzato, Daniela Bartoletti, Francesca Palandri, Giulia Benevolo, Mauro Krampera, Malgorzata Monika Trawinska, Micaela Bergamaschi, Mario Tiribelli, Giovanni Caocci, Lucia Catani, Elisabetta Abruzzese, Massimo Breccia, Rossella Stella, Antonio Cuneo, Fabio D'Amore, Alessandro Isidori, Costanza Bosi, Monica Crugnola, Lisa Gandolfi, Domenico Russo, Alessandra Iurlo, Nicola Polverelli, Roberto M. Lemoli, Michele Cavo, Gianni Binotto, Roberto Latagliata, Francesco Cavazzini, Bruno Martino, Daniele Cattaneo, Nicola Vianelli, Novella Pugliese, Luigi Scaffidi, Massimiliano Bonifacio, Mariella D'Adda, Alessia Tieghi, Giuseppe Auteri, Giuseppe A. Palumbo, Polverelli N., Elli E.M., Abruzzese E., Palumbo G.A., Benevolo G., Tiribelli M., Bonifacio M., Tieghi A., Caocci G., D'Adda M., Bergamaschi M., Binotto G., Heidel F.H., Cavazzini F., Crugnola M., Pugliese N., Bosi C., Isidori A., Bartoletti D., Auteri G., Latagliata R., Gandolfi L., Martino B., Scaffidi L., Cattaneo D., D'Amore F., Trawinska M.M., Stella R., Markovic U., Catani L., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Vianelli N., Breccia M., Russo D., Cavo M., Iurlo A., and Palandri F.
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Male ,Ruxolitinib ,Skin Neoplasms ,Lymphoma ,ruxolitinib ,Aggressive lymphoma ,Gastroenterology ,Hydroxycarbamide ,0302 clinical medicine ,myelofibrosi ,Risk Factors ,Neoplasms ,80 and over ,Aged, 80 and over ,Thrombocytosis ,Incidence (epidemiology) ,Incidence ,Hazard ratio ,Neoplasms, Second Primary ,Hematology ,Arteries ,Middle Aged ,Second Primary ,JAK inhibitor ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Context (language use) ,myelofibrosis ,JAK inhibitors ,second cancer ,toxicity ,NO ,03 medical and health sciences ,Internal medicine ,Nitriles ,medicine ,Humans ,Janus Kinase Inhibitors ,Myelofibrosis ,Aged ,Retrospective Studies ,business.industry ,Thrombosis ,medicine.disease ,Case-Control Studies ,Follow-Up Studies ,Multivariate Analysis ,Primary Myelofibrosis ,Pyrazoles ,Pyrimidines ,business ,030215 immunology - Abstract
Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P=0·01] and thrombocytosis>400×109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17–8·75, P=0·02 and HR: 2·93, 95%CI: 1·39–6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P=0·03), platelet>400×109/l (HR: 3·30, 95%CI: 1·67–6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.
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- 2020
13. Frequency of thrombosis is higher in MPN patients who develop second cancer than in controls
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Rossella R. Cacciola, Daniele Cattaneo, Manuel Pérez-Encinas, Tiziano Barbui, Clemency Stephenson, Luigi Scaffidi, Nicola Vianelli, Elisa Rumi, Maria Laura Fox, Miroslava Palova, Francesca Lunghi, Ilaria Carola Casetti, Giuseppe Carli, Elena Rossi, Ambra Di Veroli, Massimiliano Bonifacio, Alessandro Rambaldi, Daniel Erez, Alessandro M. Vannucchi, Eloise Beggiato, Montse Gómez, Paola Guglielmelli, Elena Maria Elli, Martin Griesshammer, Alberto Alvarez-Larrán, Valerio De Stefano, Francesca Palandri, Anna Angona, Alessandra Iurlo, Arianna Masciulli, Guido Finazzi, Giulia Benevolo, Valle Recasens, Davide Rapezzi, Arianna Ghirardi, Kai Wille, Silvia Betti, Andrea Patriarca, Monia Marchetti, Mary Frances McMullin, Alessandra Carobbio, and Alessia Tieghi
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medicine.medical_specialty ,business.industry ,Immunology ,Cancer ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Thrombosis ,Pulmonary embolism ,Log-rank test ,Venous thrombosis ,Leukemia ,Internal medicine ,medicine ,Carcinoma ,Thrombus ,business - Abstract
Introduction Malignancy can be heralded by unprovoked venous thromboembolism (VTE) but also by arterial thrombosis. To date it is unknown whether this association is present also in myeloproliferative neoplasms (MPN), in which arterial thrombosis is more frequent that venous thrombosis and solid tumors are reported with an increased frequency. The MPN-K nested case-control study addressed the impact of cytoreductive drugs on the risk of developing second cancer in MPN patients (Barbui T et al, Leukemia 2019); here we re-examined the study database to evaluate the frequency and type of vascular complications in MPN patients with second cancer excluding leukemia and to establish whether arterial and venous thrombosis during follow-up after diagnosis of MPN could predict the occurrence of a second cancer. Patients and methods Cases were patients with second cancer diagnosed concurrently or subsequent to the diagnosis of MPN. Controls were MPN patients without second cancer. For each case with second cancer, up to 3 cancer-free controls were matched by each center for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. Each set consisting of one case and their matched-controls had a similar observational period (from MPN diagnosis until the index date of diagnosis for the second cancer). The study included 647 cases with second cancer (carcinoma, non-melanoma-skin cancers, hematological secondary cancer and melanoma). The most frequent category was carcinoma (n=426, 65.8%). Cases were comparable with the 1,234 matched controls for demographics, type of MPN, and exposure to potential confounders such as mutational profile, abnormal karyotype and cardiovascular risk factors. The thrombotic events of interest were ischemic stroke, transient ischemic attacks, acute coronary syndromes, peripheral arterial thrombosis, deep venous thrombosis (including thrombosis of cerebral and splanchnic veins) and pulmonary embolism. Thrombosis had to be concurrent with or in the 2 years before MPN diagnosis or occurring after MPN diagnosis. The cumulative incidence of either arterial or venous thrombosis from MPN diagnosis was estimated by the Kaplan-Meier method and was compared between cases and controls using the log-rank test. A conditional logistic regression model estimated the Odds Ratio (OR) with 95% Confidence Interval (CI) of second cancer associated with the occurrence of thrombosis before/at diagnosis of MPN and during follow-up. Other covariates were patient age, cardiovascular risk factors, the JAK2V617F mutation, and treatment during follow-up. Results Approximately 20% of either MPN cases or controls had thrombosis before MPN or at diagnosis (19.8% vs. 21.1%, respectively, p=0.462). After a median observation time from diagnosis of MPN to an index date of 4.5 years (interquartile range 1.5-8.2) in cases and 3.7 years (interquartile range 1.5-7.5) in controls, cases showed a percentage of thrombosis higher than in controls (75/647, 11.6% vs. 100/1234, 8.1%, respectively, p=0.013). Approximately one-third of thrombosis preceding cancer occurred in the 12 months before the diagnosis of second cancer (22/75, 29.3%). The excess of thrombosis in cases was due to a higher frequency of arterial thrombosis (6.2% vs. 3.7%, p=0.015), whereas no significant difference was found for venous thrombosis (5.4% vs. 4.3%, p=0.277). While the cumulative incidence of venous thrombosis over time was similar among cases and controls (p=0.864), the cumulative incidence of arterial thrombosis was higher in cases with second cancer (p=0.006) (Figure 1). The excess of arterial thrombosis after MPN diagnosis was limited to cases with carcinoma (6.8% vs 3.9%, p=0.027). In a multivariable model, arterial thrombosis during the follow-up was confirmed to be an independent predictor factor for carcinoma, with an odds ratio of 1.97 (95%CI 1.14-3.41, p=0.015). Conclusions. These findings reveal an association of arterial thrombosis with subsequent second cancer (namely carcinoma) in MPN patients. A possible biological plausibility for this link may be related to an underlying common pathogenic mechanism such as an aberrant inflammatory response consistently found in MPN. This observation may have practical implications and suggests careful clinical surveillance for early diagnosis of second cancer in MPN patients with arterial thrombosis during the follow-up. Disclosures Palandri: Novartis: Consultancy, Honoraria. Iurlo:Novartis: Other: Speaker Honoraria; Incyte: Other: Speaker Honoraria; Pfizer: Other: Speaker Honoraria. Bonifacio:Incyte: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Rumi:novartis: Honoraria, Research Funding. Elli:Novartis: Membership on an entity's Board of Directors or advisory committees. Lunghi:Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria. Benevolo:Novartis Pharmaceuticals: Consultancy. McMullin:Italopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; Daiko Sanyo: Membership on an entity's Board of Directors or advisory committees. Griesshammer:Novartis: Consultancy, Honoraria, Speakers Bureau. Vannucchi:CTI: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Rambaldi:Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau.
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- 2019
14. GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia
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Maria Irno-Consalvo, Roberto Cairoli, William Arcese, Debora Capelli, Serena Lavorgna, Nicola Stefano Fracchiolla, Giovanni Martinelli, Luca Maurillo, Francesco Lo-Coco, Prassede Salutari, Francesco Buccisano, Marco Vignetti, Maria Teresa Voso, Maria Paola Martelli, Alessia Tieghi, Gabriella Storti, Edoardo La Sala, Paola Fazi, Tiziana Ottone, Lorella Melillo, Francesco Fabbiano, Caterina Alati, Anna Candoni, Francesco Lanza, Anna Chierichini, Mario Luppi, Antonio Cuneo, Agostino Tafuri, Adriano Venditti, Francesco Albano, Maria Ilaria Del Principe, Patrizio Mazza, Valeria Calafiore, Sergio Amadori, Robin Foà, Paolo de Fabritiis, Alfonso Piciocchi, Adriano, V, Alfonso, P, Anna, C, Lorella, M, Valeria, C, Cairoli, R, Paolo De, F, Gabriella, S, Prassede, S, Francesco, L, Giovanni, M, Mario, L, Patrizio, M, Maria Paola, M, Antonio, C, Francesco, A, Francesco, F, Agostino, T, Alessia, T, Nicola, S, Debora, C, Robin, F, Caterina, A, Edoardo la, S, Paola, F, Marco, V, Luca, M, Francesco, B, Maria Ilaria Del, P, Maria, I, Tiziana, O, Serena, L, Maria Teresa, V, Francesco Lo, C, William, A, and Sergio, A
- Subjects
Oncology ,Myeloid ,Male ,Neoplasm, Residual ,medicine.medical_treatment ,Salvage therapy ,Hematopoietic stem cell transplantation ,Biochemistry ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Age Factor ,Molecular Targeted Therapy ,Precision Medicine ,Etoposide ,Leukemia ,Remission Induction ,acute myeloid leukemia ,young adults ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Hematology ,Induction Chemotherapy ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Residual ,Female ,medicine.drug ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Prognosi ,Immunology ,Acute ,Risk Assessment ,NO ,Cytogenetics ,Young Adult ,Internal medicine ,medicine ,Humans ,Cytogenetic ,Consolidation Chemotherapy ,business.industry ,Induction chemotherapy ,Cell Biology ,Minimal residual disease ,Cytarabine ,acute myeloid leukemia Minimal Measurable Disease Risk-adapted therapy ,Neoplasm ,business ,Settore MED/15 - Malattie del Sangue - Abstract
We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD. Three hundred sixty-one of 500 patients (72%) achieved a complete remission, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to AlloSCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or AlloSCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, and 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRD-negative categories. In the IR MRD-positive category, AlloSCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, AlloSCT was delivered to 71% of the candidates.This trial was registered at www.clinicaltrials.gov as #NCT01452646 and EudraCT as #2010-023809-36.
- Published
- 2019
15. Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study
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Manuel Pérez-Encinas, Alessia Tieghi, Rossella R. Cacciola, Mary Frances McMullin, Miroslava Palova, Giulia Benevolo, Alessandra Carobbio, Alberto Alvarez-Larrán, Giuseppe Carli, Eloise Beggiato, Nicola Vianelli, Clemency Stephenson, Arianna Masciulli, Ambra Di Veroli, Arianna Ghirardi, Andrea Patriarca, Monia Marchetti, Tiziano Barbui, Silvia Betti, Montse Gómez, Guido Finazzi, Massimiliano Bonifacio, Valerio De Stefano, Elisa Rumi, Federica Delaini, Elena Maria Elli, Francesca Palandri, Valle Recasens, Alessandra Iurlo, Luigi Scaffidi, Kai Wille, Anna Angona, Daniele Cattaneo, Daniel Erez, Francesca Lunghi, Ilaria Carola Casetti, Paola Guglielmelli, Laura Bertolotti, Alessandro M. Vannucchi, Martin Griesshammer, and Maria Laura Fox
- Subjects
0301 basic medicine ,Cancer Research ,Ruxolitinib ,medicine.medical_specialty ,Antineoplastic Agents ,Myeloproliferative neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Essential ,SDG 3 - Good Health and Well-being ,Internal medicine ,Case-Control Studies ,Humans ,Hydroxyurea ,Neoplasms, Second Primary ,Pipobroman ,Polycythemia Vera ,Primary Myelofibrosis ,Pyrazoles ,Thrombocythemia, Essential ,Philadelphia Chromosome ,Neoplasms ,Nitriles ,medicine ,Carcinoma ,Thrombocythemia ,Myeloproliferative neoplasm ,business.industry ,Absolute risk reduction ,Cancer ,Hematology ,medicine.disease ,Settore MED/15 - MALATTIE DEL SANGUE ,Pyrimidines ,030104 developmental biology ,Second Primary ,Oncology ,030220 oncology & carcinogenesis ,Nested case-control study ,Skin cancer ,business ,medicine.drug - Abstract
We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00-14.01), ruxolitinib (OR = 3.87, 95% CI 1.18-12.75), and for drug combination (OR = 3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.
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- 2019
16. Impact of cytoreductive drugs on second cancer in myeloproliferative neoplasms
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Tiziano, Brbui, Arianna, Ghirardi, Arianna, Masciulli, Alessandra, Carobbio, Francesca, Palandri, Nicola, Vianelli, Valerio De STefano, Silvia, Betti, Ambra Di Veroli, Alessandra, Iurlo, Danile, Cattaneo, Federica, Delaini, Massimiliano, Bonifacio, Luigi, Scaffidi, Andrea, Patriarca, Elisa, Rumi, Clemency, Stephenson, Paola, Guglielmelli, Elena Maria Elli, Palova, Mirosclava, Laura, Bertolotti, Daniel, Erez, Montse, Gomez, Kai, Wille, Manuel, Perez-Encinas, Francesca, Lunghi, Anna, Angona, Maria Laura Fox, Eloise, Beggiato, Giulia, Benevolo, Giuseppe, Carli, Cacciola, Rossella Rosaria, Mary Frances McMullin, Alessia, Tieghi, Valle, Recanses, Monia, Marchetti, Martin, Griesshammer, Alberto, Alvarez-Larran, Alessandro, Vannucchi, and Guido, Finazzi
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- 2019
17. Impact of 2016 WHO diagnosis of early and overt primary myelofibrosis on presentation and outcome of 232 patients treated with ruxolitinib
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Elisabetta Abruzzese, Nicola Vianelli, Massimiliano Bonifacio, Elena Maria Elli, Giulia Benevolo, Antonio Cuneo, Francesca Palandri, Monica Crugnola, Nicola Sgherza, Robin Foà, Mario Tiribelli, Massimo Breccia, Alessandra Iurlo, Daniela Bartoletti, Alessandro Isidori, Mauro Krampera, Giuseppe A. Palumbo, Alessia Tieghi, Nicola Polverelli, Roberto M. Lemoli, Giuseppe Auteri, Gianni Binotto, Florian H. Heidel, Micaela Bergamaschi, Michele Cavo, Roberto Latagliata, Bruno Martino, Francesco Cavazzini, Daniele Cattaneo, Costanza Bosi, Palandri, Francesca, Palumbo, Giuseppe A, Abruzzese, Elisabetta, Iurlo, Alessandra, Polverelli, Nicola, Elli, Elena, Bonifacio, Massimiliano, Bergamaschi, Micaela, Martino, Bruno, Tiribelli, Mario, Benevolo, Giulia, Tieghi, Alessia, Sgherza, Nicola, Isidori, Alessandro, Binotto, Gianni, Crugnola, Monica, Heidel, Florian, Cavazzini, Francesco, Bosi, Costanza, Auteri, Giuseppe, Cattaneo, Daniele, Foà, Robin, Lemoli, Roberto M, Cuneo, Antonio, Krampera, Mauro, Bartoletti, Daniela, Cavo, Michele, Vianelli, Nicola, Breccia, Massimo, and Latagliata, Roberto
- Subjects
Male ,Cancer Research ,Ruxolitinib ,EARLY PMF ,MYELOFIBROSIS ,OVERT PMF ,RUXOLITINIB ,Heart disease ,0302 clinical medicine ,Essential ,Diagnosis ,80 and over ,Thrombocythemia ,Molecular Targeted Therapy ,Aged, 80 and over ,Hematology ,General Medicine ,Organ Size ,Middle Aged ,Neoplasm Proteins ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,Female ,Thrombocythemia, Essential ,medicine.drug ,Cohort study ,Adult ,medicine.medical_specialty ,Adolescent ,Anemia ,Socio-culturale ,Antineoplastic Agents ,World Health Organization ,Diagnosis, Differential ,03 medical and health sciences ,Internal medicine ,Nitriles ,medicine ,Humans ,Myelofibrosis ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,business.industry ,Clinical Laboratory Techniques ,Retrospective cohort study ,Early Diagnosis ,Janus Kinase 2 ,Primary Myelofibrosis ,Pyrazoles ,Spleen ,medicine.disease ,Pyrimidines ,Differential ,Differential diagnosis ,business ,030215 immunology - Abstract
The 2016 WHO criteria identified early primary myelofibrosis (PMF) as an individual entity with milder clinical features and better outcome compared with overt PMF. Here, we compared early and overt PMF patients treated with ruxolitinib in terms of baseline clinical/laboratory characteristics, response, and toxicity to treatment. We observed that early-PMF patients achieve better and more stable spleen and symptoms responses, with significantly lower rates of hematological toxicities. No differences in overall and leukemia-free survival were detected between the two cohorts. The application of 2016 WHO criteria is crucial to identify those PMF patients who deserve a stricter monitoring during treatment.
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- 2019
18. Efficacy and safety of ruxolitinib in intermediate-1 IPSS risk myelofibrosis patients: Results from an independent study
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Alessia Tieghi, Massimo Breccia, Antonio Cuneo, Alessandro Isidori, Giulia Benevolo, Giuseppe A. Palumbo, Francesco Buccisano, Michele Cavo, Marco Spinsanti, Elisabetta Abruzzese, Nicola Sgherza, Gianni Binotto, Francesca Palandri, Micaela Bergamaschi, Massimiliano Bonifacio, Mario Tiribelli, Bruno Martino, Florian H. Heidel, Lydia Kallenberg, Nicola Vianelli, Roberto Latagliata, Francesco Cavazzini, Nicola Polverelli, Luigi Scaffidi, Monica Crugnola, Palandri, Francesca, Tiribelli, Mario, Benevolo, Giulia, Tieghi, Alessia, Cavazzini, Francesco, Breccia, Massimo, Bergamaschi, Micaela, Sgherza, Nicola, Polverelli, Nicola, Crugnola, Monica, Isidori, Alessandro, Binotto, Gianni, Heidel, Florian H., Buccisano, Francesco, Martino, Bruno, Latagliata, Roberto, Spinsanti, Marco, Kallenberg, Lydia, Palumbo, Giuseppe Alberto, Abruzzese, Elisabetta, Scaffidi, Luigi, Cuneo, Antonio, Cavo, Michele, Vianelli, Nicola, and Bonifacio, Massimiliano
- Subjects
Male ,Ruxolitinib ,Pediatrics ,medicine.medical_specialty ,Cancer Research ,System risk ,Constitutional symptoms ,Anemia ,ruxolitinib ,Socio-culturale ,myelofibrosis ,Prognostic score ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,intermediate-1 risk ,IPSS ,MF ,Hematology ,Oncology ,Nitriles ,medicine ,Humans ,Adverse effect ,Myelofibrosis ,Aged ,business.industry ,Myelofibrosi ,General Medicine ,Prognosis ,medicine.disease ,Pyrimidines ,Treatment Outcome ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Pyrazoles ,Female ,business ,030215 immunology ,medicine.drug - Abstract
Patients with myelofibrosis at intermediate-1 risk according to the International Prognostic Score System are projected to a relatively long survival; nonetheless, they may carry significant splenomegaly and/or systemic constitutional symptoms that hamper quality of life and require treatment. Since registrative COMFORT studies included only patients at intermediate-2/high International Prognostic Score System risk, safety and efficacy data in intermediate-1 patients are limited. We report on 70 intermediate-1 patients treated with ruxolitinib according to standard clinical practice that were evaluated for response using the 2013 IWG-MRT criteria. At 6 months, rates of spleen and symptoms response were 54.7% and 80% in 64 and 65 evaluable patients, respectively. At 3 months, ruxolitinib-induced grade 3 anemia and thrombocytopenia occurred in 40.6% and 2.9% of evaluable patients, respectively. Notably, 11 (15.9%) patients experienced at least one infectious event ≥grade 2. Most (82.6%) patients were still on therapy after a median follow-up of 27 months. These data support the need for standardized guidelines that may guide the decision to initiate ruxolitinib therapy in this risk category, balancing benefit expectations and potential adverse effects.
- Published
- 2018
19. Comparison of JAK2V617F-positive essential thrombocythaemia and early primary myelofibrosis: The impact of mutation burden and histology
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Angelo Fama, Roberto Latagliata, Michele Cavo, Massimo Breccia, Elena Sabattini, Lucia Catani, Giuseppe A. Palumbo, Nicola Vianelli, Margherita Perricone, Francesca Palandri, Marco Spinsanti, Mara Riminucci, Emanuela Ottaviani, Riccardo Valli, Loredana Villari, Nicola Polverelli, Giuliana Alimena, Giovanni Martinelli, Alessia Tieghi, Latagliata, Roberto, Polverelli, Nicola, Tieghi, Alessia, Palumbo, Giuseppe Alberto, Breccia, Massimo, Sabattini, Elena, Villari, Loredana, Riminucci, Mara, Valli, Riccardo, Catani, Lucia, Alimena, Giuliana, Ottaviani, Emanuela, Fama, Angelo, Martinelli, Giovanni, Perricone, Margherita, Spinsanti, Marco, Cavo, Michele, Vianelli, Nicola, and Palandri, Francesca
- Subjects
medicine.medical_specialty ,Cancer Research ,Multivariate analysis ,Disease ,Gastroenterology ,Allele burden ,03 medical and health sciences ,0302 clinical medicine ,V617F ,Internal medicine ,medicine ,early primary myelofibrosis ,Myelofibrosis ,Outcome ,Acute leukemia ,Hematology ,business.industry ,PMF ,allele burden ,essential thrombocythaemia ,JAK2 ,mutation ,outcome ,Mortality rate ,Histology ,General Medicine ,medicine.disease ,Thrombosis ,Surgery ,Early primary myelofibrosi ,JAK2V617F mutation ,Early primary myelofibrosis ,Essential thrombocythaemia ,Oncology ,030220 oncology & carcinogenesis ,business ,030215 immunology - Abstract
An accurate histological diagnosis may distinguish essential thrombocythaemia (ET) from early primary myelofibrosis (early-PMF), which is associated with worse outcome. Outcome of ET is also negatively affected by the presence of the JAK2V617F mutation. To investigate the impact of JAK2V617F mutation burden and histology on outcome, we collected 475 WHO-diagnosed ET (69.2%) or early-PMF JAK2V617F-positive patients followed in 4 Italian haematology centers. JAK2V617F allele burden was ≤50% in 90% and 87% of ET and early-PMF patients, respectively (P = .34). During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28 (5.8%) patients had died. In early-PMF compared to ET, the 10-year mortality rates (6.7% and 4.3%, P = .73), leukemic transformation rates (1.4% and 1.2%, P = .45), and thrombosis rates (16.7% and 12.2%, P = .12) were comparable. Only progression to overt myelofibrosis at 10 years was significantly worse (11.4% and 1.5%, P = .004). In multivariate analysis, a higher (>50%) JAK2V617F burden was significantly correlated with fibrotic progression and histology. Considering JAK2V617F-positive disease, a higher (>50%) JAK2V617F burden and histological classification are independent prognostic risk factors for disease progression. These findings reinforce the need for standardized detection of this mutation.
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- 2018
20. Differences in presenting features, outcome and prognostic models in patients with primary myelofibrosis and post-polycythemia vera and/or post-essential thrombocythemia myelofibrosis treated with ruxolitinib. New perspective of the MYSEC-PM in a large multicenter study
- Author
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Costanza Bosi, Franco Aversa, Elisabetta Abruzzese, Nicola Vianelli, Giulia Benevolo, G. Semenzato, Bruno Martino, Daniele Cattaneo, Adalberto Ibatici, Nicola Polverelli, Daniela Bartoletti, Nicola Sgherza, Massimiliano Bonifacio, Roberto Latagliata, Francesca Palandri, Francesco Di Raimondo, Francesco Cavazzini, Micaela Bergamaschi, Michele Cavo, Massimo Breccia, Mariella D'Adda, Alessandra Iurlo, Alessandro Isidori, Maria Letizia Bacchi Reggiani, Giuseppe A. Palumbo, Luigi Scaffidi, Alessia Tieghi, Gianni Binotto, Antonio Cuneo, Monica Crugnola, Francesco Soci, Roberto M. Lemoli, Mario Tiribelli, Lucia Catani, Giuseppe Auteri, Malgorzata Monika Trawinska, Florian H. Heidel, Domenico Penna, Domenico Russo, and Palandri F, Palumbo GA, Iurlo A, Polverelli N, Benevolo G, Breccia M, Abruzzese E, Tiribelli M, Bonifacio M, Tieghi A, Isidori A, Martino B, Sgherza N, D'Adda M, Bergamaschi M, Crugnola M, Cavazzini F, Bosi C, Binotto G, Auteri G, Latagliata R, Ibatici A, Scaffidi L, Penna D, Cattaneo D, Soci F, Trawinska M, Russo D, Cuneo A, Semenzato G, Di Raimondo F, Aversa F, Lemoli RM, Heidel F, Reggiani MLB, Bartoletti D, Cavo M, Catani L, Vianelli N.
- Subjects
Ruxolitinib ,medicine.medical_specialty ,Anemia ,Socio-culturale ,Myelofibrosis ,Gastroenterology ,MYSEC-PM ,Efficacy ,03 medical and health sciences ,Essential ,0302 clinical medicine ,Polycythemia vera ,Internal medicine ,Nitriles ,Risk scores ,Humans ,Medicine ,Thrombocythemia ,Polycythemia Vera ,Survival rate ,Janus Kinases ,business.industry ,Essential thrombocythemia ,IPSS ,Myelofibrosi ,Hematology ,Prognosis ,medicine.disease ,Primary Myelofibrosis ,Pyrazoles ,Survival Rate ,Thrombocythemia, Essential ,Pyrimidines ,International Prognostic Scoring System ,030220 oncology & carcinogenesis ,Risk score ,business ,IPSS, MYSEC-PM, Myelofibrosis, Risk scores, Ruxolitinib ,030215 immunology ,medicine.drug - Abstract
Recently, the myelofibrosis secondary to PV and ET prognostic model (MYSEC-PM) was introduced to assess prognosis in myelofibrosis (MF) secondary to polycythemia vera and essential thrombocythemia (post-PV and post-ET MF), replacing the International Prognostic Scoring System (IPSS) and/or Dynamic IPSS (DIPSS) that was applied for primary MF (PMF). In a cohort of 421 ruxolitinib (RUX)-treated patients (post-PV and post-ET MF: 44.2%), we evaluated the following: (1) disease phenotype, responses, and toxicity to RUX; and (2) performance of the MYSEC-PM in post-PV or post-ET ME. While the IPSS failed to correctly stratify post-PV or post-ET MF patients at diagnosis, the MYSEC-PM identified 4 risk categories projected at significantly different survival probability (P < .001). Additionally, the MYSEC-PM maintained a prognostic value in post-PV and post-ET MF also when used over time, at RUX start. Notably, the MYSEC-PM reclassified 41.8% and 13.6% of patients into a lower and higher risk category, respectively. Finally, patients at intermediate-1 risk had significantly higher spleen responses and lower hematological toxicities compared to higher risk patients. Compared to PMF, post-PV and post-ET MF presented a more hyperproliferative disease, with higher leukocyte and/or platelet count and hemoglobin levels both at diagnosis and at RUX start. Despite comparable response rates, post-PV and post-ET MF had lower rate of RUX-induced anemia and thrombocytopenia at 3 and 6 months. The study validates MYSEC-PM in post-PV and post-ET MF prognostication. Post-PV or post-ET MF represents a separate entity compared to PMF in terms of clinical manifestations and toxicity to RUX. (C) 2018 Elsevier Inc. All rights reserved.
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- 2018
21. Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients
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Nicola, Polverelli, Massimo, Breccia, Giulia, Benevolo, Bruno, Martino, Alessia, Tieghi, Roberto, Latagliata, Elena, Sabattini, Mara, Riminucci, Laura, Godio, Lucia, Catani, Maura, Nicolosi, Margherita, Perricone, Daria, Sollazzo, Gioia, Colafigli, Anna, Campana, Francesco, Merli, Umberto, Vitolo, Giuliana, Alimena, Giovanni, Martinelli, Russell E, Lewis, Nicola, Vianelli, Michele, Cavo, Francesca, Palandri, Polverelli, Nicola, Breccia, Massimo, Benevolo, Giulia, Martino, Bruno, Tieghi, Alessia, Latagliata, Roberto, Sabattini, Elena, Riminucci, Mara, Godio, Laura, Catani, Lucia, Nicolosi, Maura, Perricone, Margherita, Sollazzo, Daria, Colafigli, Gioia, Campana, Anna, Merli, Francesco, Vitolo, Umberto, Alimena, Giuliana, Martinelli, Giovanni, Lewis, Russell E., Vianelli, Nicola, Cavo, Michele, and Palandri, Francesca
- Subjects
Adult ,Aged, 80 and over ,Male ,Incidence ,Hematology ,Janus Kinase 2 ,Middle Aged ,Communicable Diseases ,Communicable Disease ,Cohort Studies ,Primary Myelofibrosi ,Pyrimidines ,Primary Myelofibrosis ,Retrospective Studie ,Risk Factors ,Nitriles ,Pyrazole ,Humans ,Pyrazoles ,Female ,Cohort Studie ,Retrospective Studies ,Aged ,Human - Abstract
Although infectious complications represent a relevant cause of morbidity and mortality in patients with myelofibrosis (MF), little is known about their incidence, outcome and risk factors. We retrospectively evaluated a cohort of 507 MF patients, diagnosed between 1980 and 2014 in five Italian hematology centers, to define the epidemiology of infections and describe the impact of ruxolitinib (RUX) treatment. Overall, 112 patients (22%) experienced 160 infectious events (grade 3-4, 45%) for an incidence rate of 3.9% per patient-year. Infections were mainly bacterial (78%) and involving the respiratory tract (52% of cases). Also, viral (11%) and fungal infections (2%) were recorded. Overall, infections were fatal in 9% of the cases. Among baseline features, high/intermediate-2 IPSS category (HR 1.8, 95%CI:1.2-2.7; P = 0.02) and spleen length ≥10 cm below left costal margin (HR 1.6, 95%CI:1.1-2.5; P = 0.04) were associated with higher infectious risk in multivariate analysis. Overall, the rate of infections was higher in the cohort of 128 RUX-treated patients (44% vs. 20%, P
- Published
- 2017
22. Benefit-risk profile of hydroxyurea and antithrombotic treatment after transient ischemic attack or ischemic stroke in myeloprolifertive neoplasms
- Author
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Valerio De Stefano, Alessandra, Carobbio, Vincenzo Di Lazzaro, Paola, Giglielmelli, Alessandrte, Iurlo, Maria Chiara Finazzi, Elisa, Rumi, Francosco, Cervantes, Elena Maria Elli, Maria Luigia Randi, Martin, Griesshammer, Francesca, Palandri, Massimiliano, Bonifacio, Juan-Carlos, Hernandez-Boluda, Cacciola, Rossella Rosaria, Palova, Miroslava, Giuseppe, Carli, Eloise, Beggiato, Ellis, Martin H., Caterina, Musolino, Gianluca, Gaidano, Davide, Rapezzi, Alessia, Tieghi, Francesca, Lunghi, Giuseppe, Loscocco, Daniele, Cattaneo, Agostino, Cortelezzi, Silvia, Betti, Elena, Rossi, Giudo, Finazzi, Bruno, Censori, Mario, Cazzola, Marta, Bellini, Eduardo, Arellano-Rodrigo, Irene, Bertozzi, Parvis, Sadjadian, Nicola, Vianelli, Luigi, Scaffidi, Montse, Gomez, Cacciola, Emma, Vannucchi, Alessandro M., and Tiziano, Barbui
- Published
- 2017
23. Baseline factors associated with response to ruxolitinib: An independent study on 408 patients with myelofibrosis
- Author
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Micaela Bergamaschi, Alessia Tieghi, Bruno Martino, Monica Crugnola, Massimo Breccia, Adalberto Ibatici, Nicola Vianelli, Massimiliano Bonifacio, Giulia Benevolo, Mariella D'Adda, Barbara Anaclerico, Michele Cavo, Marco Spinsanti, Elisa Cerqui, Roberto Latagliata, Francesco Cavazzini, Elisabetta Abruzzese, Giuseppe A. Palumbo, Federico De Marchi, Giovanna De Matteis, Costanza Bosi, Roberto M. Lemoli, Franco Aversa, Elena Sabattini, Ambra Di Veroli, Francesco Di Raimondo, Renato Fanin, Luigi Scaffidi, Maria Letizia Bacchi Reggiani, Antonio Cuneo, Domenico Russo, Mario Tiribelli, Lucia Catani, Francesca Palandri, Umberto Vitolo, Nicola Polverelli, Francesco Merli, Palandri, Francesca, Palumbo, Giuseppe Alberto, Bonifacio, Massimiliano, Tiribelli, Mario, Benevolo, Giulia, Martino, Bruno, Abruzzese, Elisabetta, D'Adda, Mariella, Polverelli, Nicola, Bergamaschi, Micaela, Tieghi, Alessia, Cavazzini, Francesco, Ibatici, Adalberto, Crugnola, Monica, Bosi, Costanza, Latagliata, Roberto, Di Veroli, Ambra, Scaffidi, Luigi, de Marchi, Federico, Cerqui, Elisa, Anaclerico, Barbara, De Matteis, Giovanna, Spinsanti, Marco, Sabattini, Elena, Catani, Lucia, Aversa, Franco, Di Raimondo, Francesco, Vitolo, Umberto, Lemoli, Roberto Massimo, Fanin, Renato, Merli, Francesco, Russo, Domenico, Cuneo, Antonio, Bacchi Reggiani, Maria Letizia, Cavo, Michele, Vianelli, Nicola, and Breccia, Massimo
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medicine.medical_specialty ,Ruxolitinib ,Bone marrow transplant ,Socio-culturale ,Myelofibrosis ,Clinical biochemistry ,predictive factor ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,myelofibrosi ,Internal medicine ,medicine ,myelofibrosis ,predictive factors ,response ,ruxolitinib ,splenomegaly ,Hematology ,business.industry ,Response ,University hospital ,medicine.disease ,Transplantation ,Oncology ,030220 oncology & carcinogenesis ,Splenomegaly ,Predictive factors ,Clinical Research Paper ,business ,030215 immunology ,medicine.drug - Abstract
// Francesca Palandri 1 , Giuseppe Alberto Palumbo 2 , Massimiliano Bonifacio 3 , Mario Tiribelli 4 , Giulia Benevolo 5 , Bruno Martino 6 , Elisabetta Abruzzese 7 , Mariella D’Adda 8 , Nicola Polverelli 9 , Micaela Bergamaschi 10 , Alessia Tieghi 11 , Francesco Cavazzini 12 , Adalberto Ibatici 13 , Monica Crugnola 14 , Costanza Bosi 15 , Roberto Latagliata 16 , Ambra Di Veroli 17 , Luigi Scaffidi 3 , Federico de Marchi 4 , Elisa Cerqui 8 , Barbara Anaclerico 18 , Giovanna De Matteis 19 , Marco Spinsanti 1 , Elena Sabattini 1 , Lucia Catani 1 , Franco Aversa 14 , Francesco Di Raimondo 2 , Umberto Vitolo 5 , Roberto Massimo Lemoli 10 , Renato Fanin 4 , Francesco Merli 11 , Domenico Russo 9 , Antonio Cuneo 12 , Maria Letizia Bacchi Reggiani 20 , Michele Cavo 1 , Nicola Vianelli 1 and Massimo Breccia 16 1 Institute of Hematology “L. and A. Seragnoli”, Sant'Orsola-Malpighi University Hospital, Bologna, Italy 2 Division of Hematology, AOU 'Policlinico-V.Emanuele', Catania, Italy 3 Department of Hematology, University of Verona, Verona, Italy 4 Division of Hematology and BMT, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy 5 Division of Hematology, Citta della Salute e della Scienza Hospital, Torino, Italy 6 Division of Hematology, Azienda Ospedaliera 'Bianchi Melacrino Morelli', Reggio Calabria, Italy 7 Division of Hematology, Ospedale S. Eugenio, Roma, Italy 8 Division of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy 9 Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili di Brescia, Brescia, Italy 10 Division of Hematology, IRCCS AOU San Martino-IST, Genova, Italy 11 Department of Hematology, A.O. Arcispedale Santa Maria Nuova – IRCCS, Reggio Emilia, Italy 12 Division of Hematology, University of Ferrara, Ferrara, Italy 13 Division of Hematology and Bone Marrow Transplant, IRCCS San Martino-IST, Genova, Italy 14 Division of Hematology, AOU of Parma, Parma, Italy 15 Department of Hematology and Bone Marrow Transplantation, A.O. of Piacenza, Italy 16 Division of Cellular Biotechnologies and Hematology, University Sapienza, Roma, Italy 17 Division of Hematology, Policlinico Tor Vergata, Roma, Italy 18 Division of Hematology, Ospedale S. Giovanni, Roma, Italy 19 Department of Life and Reproduction Sciences, Section of Clinical Biochemistry, University of Verona, Verona, Italy 20 Division of Cardiology, University of Bologna, Bologna, Italy Correspondence to: Francesca Palandri, email: francesca.palandri@unibo.it Keywords: myelofibrosis, splenomegaly, response, ruxolitinib, predictive factors Received: March 29, 2017 Accepted: May 15, 2017 Published: June 27, 2017 ABSTRACT In patients with Myelofibrosis (MF) treated with ruxolitinib (RUX), the response is unpredictable at therapy start. We retrospectively evaluated the impact of clinical/laboratory factors on responses in 408 patients treated with RUX according to prescribing obligations in 18 Italian Hematology Centers. At 6 months, 114 out of 327 (34.9%) evaluable patients achieved a spleen response. By multivariable Cox proportional hazard regression model, pre-treatment factors negatively correlating with spleen response were: high/intermediate-2 IPSS risk ( p =0.024), large splenomegaly ( p =0.017), transfusion dependency ( p =0.022), platelet count 2 years ( p =0.048). Also, patients treated with higher (≥10 mg BID) average RUX doses in the first 12 weeks achieved higher response rates ( p =0.019). After adjustment for IPSS risk, patients in spleen response at 6 months showed only a trend for better survival compared to non-responders. At 6 months, symptoms response was achieved by 85.5% of 344 evaluable patients; only a higher (>20) Total Symptom Score significantly correlated with lower probability of response ( p
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- 2017
24. Efficacy and Safety of Ruxolitinib in Elderly Patients (> 75 years) with Myelofibrosis
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Adalberto Ibatici, Francesca Palandri, Massimiliano Bonifacio, Bruno Martino, Barbara Anaclerico, Margherita Perricone, Costanza Bosi, Mariella D'Adda, Luca Petriccione, Monica Crugnola, Michele Cavo, Giulia Benevolo, Micaela Bergamaschi, Nicola Polverelli, Ambra Di Veroli, Mario Tiribelli, Giuseppe A. Palumbo, Massimo Breccia, Nicola Vianelli, Alessia Tieghi, Alessandro Andriani, Malgorzata Monika Trawinska, Marco Montanaro, Roberto Latagliata, Francesco Cavazzini, and Antonia Centra
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medicine.medical_specialty ,Ruxolitinib ,Anemia ,ruxolitinib ,Immunology ,Population ,Socio-culturale ,myelofibrosis ,elderly patients ,comorbidities ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,medicine ,education ,Myelofibrosis ,education.field_of_study ,Acute leukemia ,business.industry ,Cell Biology ,Hematology ,medicine.disease ,Discontinuation ,030220 oncology & carcinogenesis ,Cohort ,myelofibrosis, ruxolitinib, elderly patients, comorbidities ,business ,030215 immunology ,medicine.drug - Abstract
Background. Ruxolitinib (RUX) is the first commercially available JAK1/2 inhibitor that may control splenomegaly and systemic symptoms related to myelofibrosis (MF). Despite MF occur frequently in elderly patients (pts), no data are yet available on RUX efficacy and safety in this particularly frail population. Methods We report on 100 pts [M/F 57/43, median age at diagnosis 75.7 years, interquartile range (IQR) 72.3 - 78.0, median age at baseline of RUX treatment 77.7 years, IQR 76.2 - 80.3] with WHO-defined MF treated with RUX when aged ≥ 75 years. Data were extracted from the whole cohort of 408 pts of any age collected in a database involving 22 Italian Centers. Comorbidities were recorded at the time of diagnosis and classified according to the Charlson Comorbidity Index (CCI). Response to RUX was evaluated according to IWG-MRT criteria. Results Main clinical features after stratification according to age at RUX start are reported in Table 1. Compared to younger pts, elderly pts carried a higher number of co-morbidities and had lower hemoglobin and platelet values, thus starting RUX with lower doses. Time from diagnosis to RUX start was comparable among the two cohorts (median 15.5 months, IQR 4.6 - 66.7, vs 20.8 months, IQR 4.1 - 66.0, p=0.74). According to IWG criteria, a spleen response was achieved by 37 out of 90 (41.1%) evaluable elderly pts compared to 115 out of 272 (42.2%) pts Drug-related anemia (Hb Evolution into acute leukemia occurred in 8 (8.0%) elderly pts and in 22 (7.1%) younger pts, respectively (p=0.78), with a similar evolution-free survival from RUX initiation (p=0.35). As expected, 43 (43.0%) elderly pts and 53 (17.3%) younger pts died (p The 4-year cumulative Event-Free Survival (taking into account: RUX discontinuation, blastic evolution and death for any cause) was 30.1% (95% CI: 16.2 - 44.0) in elderly pts and 46.1% (95% CI 37.3 - 54.9) in younger subjects, respectively (p=0.002). Conclusions. Despite the elderly carried a higher number of comorbidities and were treated with lower starting and titrated doses of RUX,RUX was feasible and effective in this setting, achieving clinical responses similar to younger subjects, with comparable toxicity rates. Thus, the study do not support to restrain the use of RUX based on older age and comorbidities. Figure Figure. Disclosures Latagliata: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria. Bonifacio:Ariad Pharmaceuticals: Consultancy; Amgen: Consultancy; Bristol Myers Squibb: Consultancy; Pfizer: Consultancy; Novartis: Research Funding. Tiribelli:Novartis: Consultancy, Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau. Cavo:Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding. Breccia:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria; Pfizer: Honoraria.
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- 2016
25. Predictors for Response to Ruxolitinib in Real-Life: An Observational Independent Study on 408 Patients with Myelofibrosis
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Francesco Merli, Federico De Marchi, Adalberto Ibatici, Elisa Cerqui, Micaela Bergamaschi, Michele Cavo, Francesco Di Raimondo, Umberto Vitolo, Bruno Martino, Giulia Benevolo, Barbara Anaclerico, Massimo Breccia, Nicola Polverelli, Renato Fanin, Mario Tiribelli, Costanza Bosi, Giuseppe A. Palumbo, Luigi Scaffidi, Monica Crugnola, Elisabetta Abruzzese, Mariella D'Adda, Roberto M. Lemoli, Nicola Vianelli, Francesca Palandri, Ambra Di Veroli, Roberto Latagliata, Massimiliano Bonifacio, Francesco Cavazzini, Antonio Cuneo, Alessia Tieghi, and Domenico Russo
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Ruxolitinib ,medicine.medical_specialty ,ruxolitinib ,Immunology ,Socio-culturale ,myelofibrosis ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,myelofibrosis, ruxolitinib, predictors of response ,Disease severity ,Internal medicine ,medicine ,In real life ,Myelofibrosis ,Univariate analysis ,business.industry ,Disease progression ,Cell Biology ,Hematology ,medicine.disease ,predictors of response ,030220 oncology & carcinogenesis ,Observational study ,business ,Bristol-Myers ,030215 immunology ,medicine.drug - Abstract
Background: Response to ruxolitinib (RUX), the only JAK1/2 inhibitor commercially available for the treatment of Myelofibrosis (MF) may vary among patients (pts) and is largely unpredictable at therapy start. Therefore, pts' selection is based only on clinical needs. Aims: To evaluate the impact of pre-treatment clinical/laboratory factors, as well as RUX dose, on response to RUX in a cohort of "real-life" MF pts. Methods: A multicenter observational study on WHO-defined MF was conducted in 18 Italian Hematology Centers. Data were extracted from a database that included retrospective data on pts treated before January 2015. Subsequently, data were prospectively collected and updated at a 6-month interval.Response to RUX was evaluated according to IWG-MRT criteria. Results: Between June 2011 and Apr 2016, 408 pts with PMF (54.4%), or postET (27.7%) / post-PV (17.9%) were treated with RUX. At RUX start, baseline characteristics were (median): age, 68.5 y (range, 26.5-89); ≥65 y, 63.5%; male, 56.4%; hemoglobin (Hb), 10.7 g/dL (7-16.7); transfusion-dependence 27.9%; PLT, 256×109/L (50-1887); PLT Molecular data were available for 332 pts (81.4%) and was positive in 81% (JAK2V617F), 6.3% (CALR), 1% (MPLW515K/L); 2.7% (triple negative). 30 pts (9%) were JAK2V617Fnegative but did not receive further molecular evaluation. Karyotype was abnormal in 55 (26%) out of 210 evaluable pts (unfavorable: 8.1%). Median follow-up from MF diagnosis was 3.8 yr (0.3-29.6) and median RUX exposure was 20 mos (3-56.2). Overall, 152 out of 365 (42%) pts with spleen ≥5cm achieved a spleen response at any time during RUX therapy. At 3 and 6 mos, the response was achieved by 26.6% and 34.4% of evaluable pts, respectively. In univariate analysis, pre-treatment factors negatively correlating with spleen response were: transfusion dependence, platelet count ≤200x109/l, spleen palpable ≥10 cm below costal margin, grade 3 marrow fibrosis, intm-2/high IPSS risk and interval between MF diagnosis and RUX start ≥2y. Three variables remained significant in multivariate regression logistic analysis: large splenomegaly (HR: 2.05, 95%CI: 1.1-3.7; p=0.02), time-interval ≥2y (HR: 1.78, 95%CI:1.0-3.1; p=0.04) and transfusion dependency (HR: 1.95, 95%CI:1.0-3.7; p=0.04). Spleen response significantly correlated with the average RUX dose in the first 12 wks, with pts treated with doses ≥10 mg BID having better response rates (47.3% vs 26.6% if dose 360 pts had a TSS >10 at RUX start and 319 (88.6%) achieved a symptom response. In multivariate analysis, factors associated with worse responses were: transfusion dependency (HR: 3.15, 95%CI 1.5-6.4, p=0.001) and a baseline TSS >20 (HR: 6.7, 95%CI 3.2-13.8, p Drug-related anemia (acquisition of transfusion dependency or Hb 80 (19.6%) pts discontinued RUX because of: lack/loss of response (28.8%); drug-related toxicity (27.5%, specifically: thrombocytopenia, 16.2%; infection, 6.3%; anemia, 5%); disease progression with/without acute evolution (8.8%); death (13.8%); allogeneic transplant (8.8%); 2ndneoplasia (3.8%); other unrelated causes (8.5%). Summary/Conclusion: In a real-life setting, IWG-MRT-defined spleen and symptoms response rates were observed in 42% and 88.6% of evaluable pts, respectively. Disease severity (in terms of transfusion dependency and large splenomegaly) and a delay in RUX start ≥2yr from diagnosis identified pts with lower spleen response rates. Titrated doses Disclosures Palumbo: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Shire: Honoraria; Roche: Honoraria. Bonifacio:Novartis: Research Funding; Bristol Myers Squibb: Consultancy; Amgen: Consultancy; Ariad Pharmaceuticals: Consultancy; Pfizer: Consultancy. Tiribelli:Bristol-Myers Squibb: Consultancy, Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Latagliata:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria. Vitolo:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Gilead: Other: Honoraria for lectures; Takeda: Other: Honoraria for lectures. Fanin:Novartis: Speakers Bureau. Merli:Teva Pharmaceuticals Industries: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Cavo:Janssen-Cilag: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Breccia:Ariad: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Honoraria; Pfizer: Honoraria.
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- 2016
26. Splanchnic vein thrombosis in myeloproliferative neoplasms: Risk factors for recurrences in a cohort of 181 patients
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Silvia Betti, C. Musolino, Maria-Luigia Randi, Esther Diana Rossi, Paola Guglielmelli, Giorgina Specchia, G Finazzi, Francisco Cervantes, Ester Pungolino, Nicola Vianelli, Martin Ellis, Emma Cacciola, Juan Carlos Hernández-Boluda, Alessandra Forcina, Elena Maria Elli, Daniele Cattaneo, Alberto Alvarez-Larrán, Alessandra Carobbio, Alessandra Iurlo, Gianluca Gaidano, Martin Griesshammer, Alessia Tieghi, Eva Zetterberg, Lisa Pieri, Marco Ruggeri, T Barbui, Miroslava Palova, V. De Stefano, Maria Chiara Finazzi, Alessandro M. Vannucchi, Ilaria Nichele, and Davide Rapezzi
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Adult ,Male ,medicine.medical_specialty ,Budd-Chiari Syndrome ,030204 cardiovascular system & hematology ,myeloproliferative neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Risk Factors ,medicine ,Humans ,Trombosi ,Myelofibrosis ,Polycythemia Vera ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Tumors ,Venous Thrombosis ,First episode ,Portal Vein ,business.industry ,Hazard ratio ,Hematology ,Oncology ,Hematology, Oncology, splanchnic vein thrombosis, myeloproliferative neoplasms ,Middle Aged ,medicine.disease ,Thrombosis ,Portal vein thrombosis ,Surgery ,Settore MED/15 - MALATTIE DEL SANGUE ,Venous thrombosis ,Splanchnic vein thrombosis ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Budd–Chiari syndrome ,Original Article ,Female ,business ,Thrombocythemia, Essential - Abstract
We retrospectively studied 181 patients with polycythaemia vera (n=67), essential thrombocythaemia (n=67) or primary myelofibrosis (n=47), who presented a first episode of splanchnic vein thrombosis (SVT). Budd-Chiari syndrome (BCS) and portal vein thrombosis were diagnosed in 31 (17.1%) and 109 (60.3%) patients, respectively; isolated thrombosis of the mesenteric or splenic veins was detected in 18 and 23 cases, respectively. After this index event, the patients were followed for 735 patient years (pt-years) and experienced 31 recurrences corresponding to an incidence rate of 4.2 per 100 pt-years. Factors associated with a significantly higher risk of recurrence were BCS (hazard ratio (HR): 3.03), history of previous thrombosis (HR: 3.62), splenomegaly (HR: 2.66) and leukocytosis (HR: 2.8). Vitamin K-antagonists (VKA) were prescribed in 85% of patients and the recurrence rate was 3.9 per 100 pt-years, whereas in the small fraction (15%) not receiving VKA more recurrences (7.2 per 100 pt-years) were reported. Intracranial and extracranial major bleeding was recorded mainly in patients on VKA and the corresponding rate was 2.0 per 100 pt-years. In conclusion, despite anticoagulation treatment, the recurrence rate after SVT in myeloproliferative neoplasms is high and suggests the exploration of new avenues of secondary prophylaxis with new antithrombotic drugs and JAK-2 inhibitors. TB and AMV were supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano) ‘Special Program Molecular Clinical Oncology 5 × 1000’ to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative). VDS was supported by an unrestricted grant from the Bruno Farmaceutici Foundation.
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- 2016
27. Unbiased pro-thrombotic features at diagnosis in 977 thrombocythemic patients with Philadelphia-negative chronic myeloproliferative neolpasms
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Luigi, Gugliotta, Alessandra, Iurlo, Gabriele, Gugliotta, Alessia, Tieghi, Giogina, Specchia, Gianluca, Gaidano, Potito, R Scalzulli, Elisa, Rumi, Alfredo, Dragani, Vincenzo, Martinelli, Cristina, Santoro, Maria Luigia Randi, Giuseppe, Tagariello, Anna, Candoni, Daniele, Cattaneo, Alessandra, Ricco, Raffaele, Palmieri, Liberati, Marina A., Maria, Langella, Angela, Rago, Micaela, Bergamaschi, Paola, Monari, Rossella, Miglio, Umberto, Santoro, Cacciola, Rossella Rosaria, Cacciola, Emma, Serena, Rupoli, Lucia, Mastrullo, Pellegrino, Musto, Maria Gabriella Mazzucconi, Marco, Vignetti, Agostino, Corelezzi, Nicola, Vianelli, Bruno, Martino, Valerio De STefano, Francesco, Passamonti, Alessandro, M Vannucchi, for the Registro Italiano Trombocitemia RIT, Gugliotta, Luigi, Iurlo, Alessandra, Gugliotta, Gabriele, Tieghi, Alessia, Specchia, Giorgina, Gaidano, Gianluca, Scalzulli, Potito R., Rumi, Elisa, Dragani, Alfredo, Martinelli, Vincenzo, Santoro, Cristina, Randi, Maria Luigia, Tagariello, Giuseppe, Candoni, Anna, Cattaneo, Daniele, Ricco, Alessandra, Palmieri, Raffaele, Liberati, Marina A., Langella, Maria, Rago, Angela, Bergamaschi, Micaela, Monari, Paola, Miglio, Rossella, Santoro, Umberto, Cacciola, Rossella, Rupoli, Serena, Mastrullo, Lucia, Musto, Pellegrino, Mazzucconi, Maria Gabriella, Vignetti, Marco, Cortelezzi, Agostino, Vianelli, Nicola, Martino, Bruno, De Stefano, Valerio, Passamonti, Francesco, and Vannucchi, Alessandro M.
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Male ,Cancer Research ,Pathology ,Multivariate analysis ,Leukocytosis ,Hematocrit ,Gastroenterology ,JAK2 ,Leukocytes ,Platelets ,Thrombocythemia ,Thrombosis ,Hematology ,Oncology ,0302 clinical medicine ,Risk Factors ,Medicine ,Thrombophilia ,Platelet ,Child ,Aged, 80 and over ,Thrombocytosis ,medicine.diagnostic_test ,Middle Aged ,030220 oncology & carcinogenesis ,Thrombosi ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Adolescent ,03 medical and health sciences ,Young Adult ,Internal medicine ,Humans ,Aged ,Philadelphia negative ,Myeloproliferative Disorders ,business.industry ,Platelet Count ,Leukocyte ,medicine.disease ,Settore MED/15 - MALATTIE DEL SANGUE ,business ,030215 immunology - Abstract
In patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), the anti-thrombotic and/or cytoreductive treatment in the follow-up may affect the evaluation of the pro-thrombotic weight of the clinical and biological characteristics at diagnosis. In order to avoid this potential confounding effect, we investigated the relationship between prior thrombosis (PrTh: thrombosis occurred before diagnosis and before treatment) and the characteristics at diagnosis in 977 thrombocythemic patients with MPN, reclassified according to the WHO 2008 criteria. PrTh occurred in 194 (19.9%) patients, with similar rates in the different MPNs. In multivariate analysis, PrTh rate was significantly related to minor thrombocytosis (platelets ≤700 × 109/L), leukocytosis (leukocytes >10 × 109/L), higher hematocrit (HCT >45%), JAK2 V617F mutation, older age, and cardiovascular risk factors (CVRFs). The highest PrTh rate (33.9%) was associated with the coexistence of minor thrombocytosis and leukocytosis. Of note, the inverse relationship between PrTh rate and platelet count is consistent with the hemostatic paradox of thrombocytosis. In conclusion, this analysis in MPN patients disclosed the unbiased characteristics at diagnosis with a pro-thrombotic effect. Moreover, it suggests that the optimal control of blood cells counts, and CVRFs might be of utmost importance in the prevention of thrombosis during the follow-up.
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- 2016
28. HOW DIAGNOSTIC AND THERAPEUTIC APPROACHE CHANGED IN THE LAST DECADES IN THE PHILADELPHIA NEGATIVE MPN PATIENTS OF THE REGISTRO ITALIANO TROMBOCITEMIE (RIT)
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Gugliotta, L., Iurio, A., Gugliotta, G., Alessia Tieghi, Candoni, A., Lunghi, M., Dragani, A., Antonioli, E., Scalzulli, P. R., Martinelli, V., Martino, B., Randi, M. L., Ricco, A., Appolloni, V., Maschio, N., Palmieri, R., Langella, M., Santoro, C., Rago, A., Ragionieri, R., Codeluppi, K., Cacciola, E., Cacciola, R., Mastrullo, L., Esposito, M. R., Caocci, G., Lanza, F., Rupoli, S., Pierri, I., Porretto, F., Melpignano, A., Crugnola, M., Di Ianni, M., Plebani, S., Molinari, E., Spinosa, G., Santoro, M., Villani, O., Ricciotti, M., Musolino, C., Usala, E., Falzetti, F., Biasi, E., Santoro, U., Federici, A., Vianelli, N., Mazzucconi, M. G., and Specchia, G.
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- 2015
29. Initial Therapeutic Approach and Relationship with Clinical and Biological Characteristics at Diagnosis in 2418 Patients of the Registro Italiano Trombocitemie (RIT)
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Raffaele Palmieri, Viviana Appolloni, Bruno Martino, Daniele Cattaneo, Nicola Vianelli, Elisabetta Antonioli, Rossella R. Cacciola, Nicola Cantore, Andrea Piccin, Potito Rosario Scalzulli, Nicola Polverelli, Paola Monari, Maria Rosaria Villa, Alfredo Dragani, Umberto Santoro, Rossella Miglio, Angelo Fama, Monia Lunghi, Elisa Rumi, Ercole De Biasi, Katia Codeluppi, Alessia Tieghi, Angela Rago, Serena Rupoli, Nilla Maschio, Maria Luigia Randi, Cristina Santoro, Vincenzo Martinelli, Luigi Gugliotta, Maria Gabriella Mazzucconi, Alessandra Iurlo, Anna Candoni, Alessandra Ricco, Ivana Pierri, and Gabriele Gugliotta
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medicine.medical_specialty ,Pediatrics ,Univariate analysis ,Thrombocytosis ,Essential thrombocythemia ,business.industry ,Pipobroman ,Immunology ,Alpha interferon ,Cell Biology ,Hematology ,Anagrelide ,medicine.disease ,Biochemistry ,Gastroenterology ,Internal medicine ,medicine ,Leukocytosis ,medicine.symptom ,business ,Busulfan ,medicine.drug - Abstract
Background. The therapeutic approach in thrombocythemic patients with Philadelphia negative chronic myeloproliferative neoplasms (Ph- MPN), in order to result cost-effective (primum non nocere), is commonly driven by the risk factors considered in the gradually updated guidelines. However, no studies were addressed to evaluate if and how the real-life therapeutic approach changed in the last decades. Objective. To evaluate, in a large series of thrombocythemic patients with Ph- MPN, the impact of clinical and biological characteristics at diagnosis on the therapeutic approach adopted before and after the publication of the Italian guidelines for essential thrombocythemia therapy [1]. Methods. The analysis considered, in the patients of the Registro Italiano Trombocitemie (RIT), the clinical and biological characteristics at diagnosis, and the treatment ongoing after 3, 6, 12, and >12 months from diagnosis (antiplatelet alone [AntiPLT]; cytoreductive alone [CYT]; CYT+AntiPLT). Results. The analyzed patients were 2418, 914 (38%) males and 1504 (62%) females, with a diagnosis (PVSG or WHO criteria) performed before and after 2005 in 51% and 49% of cases, respectively. The rate of ongoing treatment with AntiPLT, CYT, and CYT+AntiPLT increased as follows: at 3rd month 16%, 12%, and 31%; at 12th month 17%, 14%, and 39%; after 12 months 19%, 16%, and 55%, respectively. Patients treated with CYT or CYT+AntiPLT did not significantly differ in their characteristics at diagnosis. The analysis of data at the 3rd month (initial phase) showed that: 1) CYT±AntiPLT treatment, ongoing in 43% of patients, was significantly related, in univariate analysis, to male gender, older age, prior thrombosis, higher thrombocytosis, leukocytosis, higher HCT level, CVRFs, comorbidities, symptoms, splenomegaly, hepatomegaly, and bone marrow fibrosis grade >0 (no relationship with JAK2 V617F mutation, and prior hemorrhage); in multivariate analysis, it was significantly related to age >60 y, age 40-60 y, prior thrombosis, PLT >1000 x109/L, PLT 700-1000 x109/L, symptoms, and comorbidities. 2) patients with standard high risk (age >60 y, and/or prior thrombosis, and/or PLT >1500 x109/L ) were receiving CYT±AntiPLT (59%), AntiPLT (7%), and no treatment (34%). 3) patients with standard low risk were receiving CYT±AntiPLT (22%), AntiPLT (27%), and no treatment (51%). Low risk patients receiving CYT±AntiPLT had age 40-60 y (73%), CVRFs (59%), symptoms (53%), comorbidities (42%), PLT 1000-1500 x109/L (35%), PLT 700-1000 x109/L (42%), JAK2 V617F mutation (30%), WBC >10 x109/L (22%). 4) in patients receiving CYT±AntiPLT, the initial cytoreductive drug and the median age were: hydroxycarbamide (80%, 68 y), anagrelide (6%, 49 y), interferon alpha (9%, 42 y), pipobroman (2%, 72 y), busulfan (3%, 70 y). The AntiPLT drug mostly used was low dose ASA (86-90% of cases, at any age). 5) Patients diagnosed after 2005, compared with those diagnosed before, showed a higher rate of CYT±AntiPLT treatment when at standard high risk ( 64% vs 53 % p Conclusion. The initial (within the 3rd month) therapeutic approach in the thrombocythemic Ph- MPN patients of the RIT was after 2005 relatively compliant with the 2004 Italian guidelines. In fact, the rate of CYT±AntiPLT treatment in patients with standard high risk was higher than before (64% vs 53%, p [1] Barbui T et al. Haematologica 2004; [2] Harrison C et al. NEJM 2005; [3] Gisslinger H et al. NEJM 2013; [4] Passamonti F et al. Blood 2012; [5] Barbui T et al. Blood 2012 *The RIT is a project of the GIMEMA Foundation Disclosures Gugliotta: Shire : Honoraria.
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- 2014
30. Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation
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Valerio De Stefano, Tommaso, Za, Elena, Rossi, Vannucchi, Alessandro M., Marco, Ruggeri, Elena, Elli, Caterina, Mico, Alessia, Tieghi, Cacciola, Rossella R., Santoro, Cristina, Nicola, Vianelli, Paola, Guglielmelli, Lisa, Pieri, Francesca, Scognamiglio, Emma, Cacciola, Francesco, Rodeghiero, Pogliani, Enrico M., Guido, Finazzi, Luigi, Gugliotta, Giuseppe, Leone, Tiziano, Barbui, Mazzucconi, Maria Gabriella, Chronic Myeloproliferative Neoplasms Working Party Gimema, Institute of Hematology, Catholic University, The Department of Hematology, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), The Hematology Department and Hemophilia and Thrombosis Center, San Bortolo Hospital, The Hematology Division and Bone Marrow Transplantation Unit, San Gerardo Hospital, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), The Department of Hematology−Oncology, Ospedali Riuniti, The Hematology Unit, Santa Maria Nuova Hospital, The Department of Biomedical Sciences, Section of Hematology, Università degli studi di Catania [Catania], The Institute of Hematology, Department of Cellular Biotechnology and Hematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], The Institute of Hematology and Oncology L. and A. Seràgnoli, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), De Stefano, V, Za, T, Rossi, E, Vannucchi, A, Ruggeri, M, Elli, E, Micò, C, Tieghi, A, Cacciola, R, Santoro, C, Vianelli, N, Guglielmelli, P, Pieri, L, Scognamiglio, F, Cacciola, E, Rodeghiero, F, Pogliani, E, Finazzi, G, Gugliotta, L, Leone, G, and Barbui, T
- Subjects
Adult ,Male ,medicine.medical_specialty ,Essential thrombocythemia ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,MED/15 - MALATTIE DEL SANGUE ,Internal medicine ,hemic and lymphatic diseases ,Medicine ,Humans ,Allele ,Risk factor ,JAK2 V617F mutation ,Aged ,Aged, 80 and over ,Hematology ,business.industry ,Hazard ratio ,essential thrombocythemia ,essential thrombocythemia - jak2 v617f mutation - recurrent thrombosis ,jak2 v617f mutation ,recurrent thrombosis ,Retrospective cohort study ,Thrombosis ,General Medicine ,Janus Kinase 2 ,Middle Aged ,medicine.disease ,3. Good health ,Surgery ,030220 oncology & carcinogenesis ,Mutation (genetic algorithm) ,Mutation ,Female ,Recurrent thrombosi ,Recurrent thrombosis ,business ,Thrombocythemia, Essential - Abstract
Evidence suggests that the JAK2 V617F mutation is associated with an increased risk of first thrombosis in patients with essential thrombocythemia (ET). Whether this mutation is also a risk factor for recurrent thrombosis is currently unknown. To investigate the impact of the JAK2 V617F mutation on the risk of recurrent thrombosis in patients with ET, we carried out a multicentre retrospective cohort study. We recruited 143 patients with previous arterial (64.4%) or venous major thrombosis (34.8%) or both (0.8%); 98 of them (68.5%) carried the mutation. Thrombosis recurred in 43 of the patients (30%); overall, after adjustment for sex, age, presence of vascular risk factors, and treatment after the first thrombosis, the presence of the JAK2 mutation did not predict recurrence (multivariable hazard ratio, HR, 0.88, 95% CI 0.46-1.68). Indeed, the individuals homozygous for the JAK2 V617F (allele burden >50%) mutation had an increased risk of recurrence in comparison with wild-type patients (HR 6.15, 95% CI 1.51-24.92). In conclusion, a homozygous JAK2 V617F mutation is an independent risk factor for recurrent thrombosis in patients with ET. © Springer-Verlag 2009.
- Published
- 2010
31. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia
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Renato Fanin, Rita Rizzi, Michele Baccarani, Patrizio Mazza, Emanuele Angelucci, Selenia Campagna, Silvia Cantoni, Enrica Gamba, Valerio De Stefano, Felicetto Ferrara, Giuseppe Visani, Marzia Defina, Franca Soldano, Sergio Amadori, Emilio Usala, Alfonso Zaccaria, Francesco Casulli, Alessia Tieghi, Antonella Fornaro, Miriam Isola, Luigi Gugliotta, Monica Bocchia, Marta Lisa Battista, Francesco Zaja, Nicola Vianelli, Zaja F, Baccarani M, Mazza P, Bocchia M, Gugliotta L, Zaccaria A, Vianelli N, Defina M, Tieghi A, Amadori S, Campagna S, FerraraF, Angelucci E, Usala E, Cantoni S, Visani G, Fornaro A, Rizzi R, Zaja, Francesco, Baccarani, M, Mazza, P, Bocchia, M, Gugliotta, L, Zaccaria, A, Vianelli, N, Defina, M, Tieghi, A, Amadori, S, Campagna, S, Ferrara, F, Angelucci, E, Usala, E, Cantoni, S, Visani, G, Fornaro, A, Rizzi, R, DE STEFANO, V, Casulli, F, Battista, Ml, Isola, Miriam, Soldano, F, Gamba, E, and Fanin, Renato
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Combination therapy ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Splenectomy ,Salvage therapy ,Biochemistry ,Gastroenterology ,Dexamethasone ,Antibodies, Monoclonal, Murine-Derived ,Refractory ,dexamethasone, purpura, thrombocytopenic, idiopathic, rituximab, salvage therapy, platelet count measurement, arm ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Adverse effect ,Aged ,Salvage Therapy ,Purpura, Thrombocytopenic, Idiopathic ,Platelet Count ,business.industry ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Middle Aged ,Surgery ,Corticosteroid ,Female ,Rituximab ,business ,Settore MED/15 - Malattie del Sangue ,medicine.drug - Abstract
Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 × 109/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m2 rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count ≥ 50 × 109/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, −0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, −0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.
- Published
- 2010
32. Leukocytosis is a risk factor for recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia
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VALERIO DE STEFANO, Tommaso, Za, Elena, Rossi, Vannucchi, ALESSANDRO M., Marco, Ruggeri, Elena, Elli, Caterina, Micò, Alessia, Tieghi, Cacciola, ROSSELLA R., Cristina, Santoro, Giancarla, Gerli, Nicola, Vianelli, Paola, Guglielmelli, Lisa, Pieri, Francesca, Scognamiglio, Francesco, Rodeghiero, Pogliani, ENRICO M., Guido, Finazzi, Luigi, Gugliotta, Giuseppe, Leone, Tiziano, Barbui, and FOR THE GIMEMA CHRONIC Myeloproliferative Neoplasms Working Party
- Published
- 2010
33. Recurrent venous thrombosis in patients with polycythemia vera and essential thrombocythemia
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VALERIO DE STEFANO, Tommaso, Za, Elena, Rossi, Elena, Elli, Vannuchi, ALESSANDRO M., Marco, Ruggeri, Caterina, Micò, Nicola, Vianelli, Cacciola, Rossella Rosaria, Alessia, Tieghi, Cristina, Santoro, Pogliani, ENRICO M., Paola, Guglielmelli, Lisa, Pieri, Francesca, Scognamiglio, Francesco, Rodeghiero, Guido, Finazzi, Luigi, Gugliotta, Giuseppe, Leone, Tiziano, Barbui, and FOR THE GIMEMA CMD WORKING PARTY
- Published
- 2007
34. Thrombotic and hemorrhagic complications after surgery in patients with essential thrombocythemia and polycythemia vera
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Cristina Santoro, Elisabetta Antonioli, Tiziano Barbui, Tommaso Za, Francesco Rodeghiero, Alessandro M. Vannucchi, Giancarlo Castaman, Marco Ruggeri, Luigi Gugliotta, Federica Delaini, Guido Finazzi, Caterina Micò, Alberto Tosetto, Maria Gabriella Mazzucconi, Francesca Scognamiglio, Alessia Tieghi, and Valerio De Stefano
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Immunology ,Warfarin ,Cell Biology ,Hematology ,Hematocrit ,medicine.disease ,Biochemistry ,Thrombosis ,Surgery ,Venous thrombosis ,Polycythemia vera ,Anesthesia ,Antithrombotic ,medicine ,Risk factor ,business ,Fibrinolytic agent ,medicine.drug - Abstract
Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative diseases characterized by frequent episodes of deep venous thrombosis (DVT), arterial thromboembolism (AT) and by hemorrhagic complications. Surgical procedures could represent a risk factor for thrombosis and bleeding, but no data on the real frequency of these complications are available. To estimate the frequency of thrombosis and haemorrhages after surgical procedures and their outcomes, a multicenters retrospective analysis was performed. Data from 105 PV and 150 ET patients (128 males, 127 females, median age at diagnosis 60, were analyzed, for a total of 311 surgical interventions. At least one risk factor for arterial thrombosis (diabetes mellitus, hypercholesterolemia, arterial hypertension, previous AT, smoke) was present in 128/255 (50.1%), more frequently in PV than in ET patients (58.5 vs. 46.8%, p=0.02). An excess of male and older patients in PV than in ET explained this finding (multivariate analysis). Previous DVT was present in 9/255 patients (3.5%). After diagnosis, antiplatelet drugs were given to 211/255 patients (82.7%); cytoreductive treatments to 188/255 (74%), warfarin to 16/255 (6.2%); all PV patients were phlebotomized. In 25/311 surgeries (8.0%), an emergency procedure was performed; 195 surgeries were done under general anaesthesia; 21/91 abdominal interventions (23%) were performed under laparoscopy. Major surgeries were 160/311 (51.4%). Data about antithrombotic prophylaxis were available for 292/311 surgeries: in 126 (43.2%) low molecular heparin, in 38 (13%) unfractioned heparin, in 5 (1.7%) warfarin and in 123 no anticoagulant therapy was administered. In 45/123 (36.6%) patients without antithrombotic prophylaxis, antiplatelet therapy was administered before surgery. 189/255 (74%) were on cytoreductive therapy before surgery; for 9 surgical procedures, a short cycle of chemotherapy was administered before surgery. Clinical outcomes after surgery were recorded with a 3 months follow-up. No event was observed in 259/311 procedures (83.2%); there were 12 arterial and 12 venous thrombotic events, 23 major and 7 minor hemorrhages and 5 deaths. AT were more frequent in ET patients (5.3 vs. 1.5%, p=0.08) while venous events were more frequent in PV patients (7.7 vs. 1.1%, p=0.002). There was a strong risk gradient for AT associated with the presence of one or more arterial risk factors (OR for 4 or more risk factors: 40.9, p=0.003). Platelet count and hematocrit at surgery (median 477 x 109 /l and 42.6%, respectively) were not associated with either venous or arterial thrombosis. There was no correlation between bleeding episodes and type of diagnosis, use of antithrombotic prophylaxis and type of surgery. In conclusion, despite an active approach (cytoreduction and antithrombotic prophylaxis in the majority of the cases) a high proportion of PV and ET surgeries was complicated by DVT and AT (7.7%) but also by major hemorrhages (7.3%), requiring more investigation on the optimal prophylaxis in these patients.
- Published
- 2006
35. Soluble urokinase-type Plasminogen Activator Receptor (suPAR) as an independent factor predicting worse prognosis and extra bone marrow involvement in multiple myeloma patients
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Gian Matteo, Rigolin, Alessia, Tieghi, Maria, Ciccone, Letizia Zenone, Bragotti, Francesco, Cavazzini, Matteo, Della Porta, Barbara, Castagnari, Rosanna, Carroccia, Giovanni, Guerra, Antonio, Cuneo, and Gianluigi, Castoldi
- Subjects
Male ,Syndecans ,Plasma Cells ,Receptors, Cell Surface ,Receptors, Urokinase Plasminogen Activator ,NO ,Antigens, CD ,Multiple myeloma ,Humans ,CD87 ,ADP-ribosyl Cyclase ,Aged ,Neoplasm Staging ,Soluble urokinase-type plasminogen activator receptor (suPAR) ,Membrane Glycoproteins ,Prognosis ,Middle Aged ,Flow Cytometry ,ADP-ribosyl Cyclase 1 ,CD56 Antigen ,Case-Control Studies ,Creatinine ,Multivariate Analysis ,Proteoglycans ,Syndecan-1 ,beta 2-Microglobulin ,Biomarkers - Abstract
The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0.038), CD38 (P = 0.058) and CD138 (P = 0.054) and CD45bright positivity (P = 0.014). suPAR levels correlated positively with soluble serum CD138 (P = 0.001), creatinine (P = 0.001), beta2-microglobulin (P0.001), disease stage (P = 0.017) and extra-BM involvement (P = 0.002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0.0214) and disease stage (P = 0.0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0.0278), high soluble serum CD138 (P = 0.0201) and high suPAR (P = 0.0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM.
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- 2003
36. Comparison of single and dual platform methodologies for the estimation of CD34+ hematopoietic progenitor cells: correlation with colony assay
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Alessia Tieghi, Melissa Dabusti, Sabrina Moretti, Diana Campioni, Luisa Ferrari, Francesco Lanza, Barbara Castagnari, Massimo Dominici, Gian Luigi Castoldi, and M Punturieri
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Adult ,Cancer Research ,Pathology ,medicine.medical_specialty ,Adolescent ,Clinical Biochemistry ,CD34 ,Antigens, CD34 ,Biology ,Pathology and Forensic Medicine ,Flow cytometry ,medicine ,Enumeration ,Humans ,flow cytometry ,hematopoietic stem cells ,transplantation ,hematology ,oncology ,Progenitor cell ,Clonogenic assay ,Chromatography ,medicine.diagnostic_test ,short term colony assay ,Middle Aged ,Fetal Blood ,Hematopoietic Stem Cells ,Cell counting ,Blood Cell Count ,Transplantation ,Oncology ,Cord blood ,hematopoietic progenitor cells - Abstract
In this study three assays for the enumeration of CD34+ progenitors were compared: 1) a modified version of the Milan protocol, used in the standard dual-platform format; 2) a dual-platform version of the ISHAGE protocol; 3) the ProCOUNT software version 2.0/ProCOUNT kit. The assays were compared to validate the accuracy of CD34+ cell counts in mobilized peripheral blood (PB), apheresis products (AP), and cord blood (CB). The ProCOUNT protocol uses reference beads for absolute CD34+ cell counting, whereas CD34 counts by other techniques are derived from a separate leukocyte count performed by a hematology analyzer. A good correlation between the ISHAGE and ProCOUNT methods was obtained for estimation of CD34+ counts in PB (n=42 samples analyzed) and AP (n=35) - except for samples having a leukocyte count >25 x 10 9 /L or a CD34 count
- Published
- 2002
37. CD34+ cell subsets and long-term culture colony-forming cells evaluated on both autologous and normal bone marrow stroma predict long-term hematopoietic engraftment in patients undergoing autologous peripheral blood stem cell transplantation
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Massimo Bacilieri, Cristiano De Angeli, Massimo Dominici, Sabrina Moretti, Francesco Lanza, Galluccio L, Gianluigi Castoldi, S Pauli, M Punturieri, Melissa Dabusti, Alessia Tieghi, Diana Campioni, Elisa Focarile, and Chiara Scapoli
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Male ,Cancer Research ,medicine.medical_treatment ,CD34 ,Antigens, CD34 ,Hematopoietic stem cell transplantation ,chemotherapy ,autologous transplantation ,Reference Values ,Antineoplastic Combined Chemotherapy Protocols ,initiating cells ,Cells, Cultured ,Lymphoma, Non-Hodgkin ,Hematopoietic Stem Cell Transplantation ,in vitro ,Hematology ,progenitor cells ,Middle Aged ,ex vivo expansion ,Hodgkin Disease ,Haematopoiesis ,limiting diluition ,Vincristine ,Female ,Stem cell ,Multiple Myeloma ,Adult ,Stromal cell ,Platelet Engraftment ,Cell Survival ,Prednisolone ,stem cell engraftment ,Biology ,ex vivo expansion, progenitor cells, limiting diluition, initiating cells, direct contact, in vitro, platelet recovery, assay, chemotherapy ,Transplantation, Autologous ,Immunophenotyping ,NO ,Colony-Forming Units Assay ,Bleomycin ,Antigens, CD ,Predictive Value of Tests ,Genetics ,medicine ,Autologous transplantation ,Humans ,platelet recovery ,Molecular Biology ,Cyclophosphamide ,Neutrophil Engraftment ,long-term culture ,Cell Biology ,assay ,Methotrexate ,Doxorubicin ,Immunology ,Cancer research ,direct contact - Abstract
Objective The aim of this study was to evaluate which CD34 + cell subset contained in leukapheresis products could be regarded as the most predictive of long-term hematopoietic recovery after autologous peripheral blood stem cell transplantation (auto-PBSCT). Materials and Methods Based on data from 34 patients with hematologic malignancies, doses of CD34 + cells and CD34 + cell subsets, defined by the expression of HLA-DR, CD38, CD117 (c-kit/R), CD123 (α subunit of IL-3/R), CD133 (AC133), and CD90 (Thy-1) antigens, were correlated with the number of short-term (i.e., colony-forming cells [CFC]) and long-term culture CFC (LTC-CFC) (generated at week 5 of culture) and with the kinetics of hematopoietic engraftment following auto-PBSCT. The capacity of autologous stroma (AS), normal human bone marrow stroma, and M2-10B4 murine cell line to sustain CD34 + cell growth was comparatively evaluated in the LTC assay. Results Our data demonstrated that some of the most primitive progenitor subsets (CD34 + CD117 − HLA-DR − , and CD34 + CD38 + HLA-DR − ) showed the strongest correlation with LTC-CFC numbers generated within the AS, whereas no significant correlation was noted using normal bone marrow stroma. Multivariate analysis showed that the only CD34 cell subset independently associated with long-term (3 to 6 months) platelet engraftment after auto-bone marrow transplantation was the CD34 + CD117 − HLA-DR − phenotype; long-term erythrocyte engraftment was correlated with CD34 + CD38 + HLA-DR − cell content. The latter further influenced platelet engraftment in the first 3 months after auto-PBSCT. The most predictive parameters for neutrophil engraftment were CD34 + CD38 + HLA-DR − cell subtype and the total LTC-CFC quantity infused. Conclusions These data further support the hypothesis that the type of stromal feeders influences the frequency of LTC-CFC, possibly because they differ in their ability to interact with distinct subsets of hematopoietic stem cells. Furthermore, as the use of AS in LTC assay can mimic in vitro the human bone marrow microenvironment, it can be speculated that this culture system could be a useful means to study the kinetics of recovery of bone marrow stroma following chemotherapy and PBSCT. From these results, it can be concluded that some CD34 + cell subsets appear to be more reliable predictors of long-term hematopoietic recovery rates than total CD34 + cell quantity.
- Published
- 2001
38. Prolonged remission state of refractory adult onset Still's disease following CD34-selected autologous peripheral blood stem cell transplantation
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Latorraca A, Marcello Govoni, Francesco Trotta, Massimo Dominici, Francesco Lanza, Gian Luigi Castoldi, Alessia Tieghi, Barbara Castagnari, Sabrina Moretti, Renato La Corte, and Diana Campioni
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Still Disease ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,stem cell transplantation ,stem cell transplantation, autoimmune diseases, Still disease, first tranplant in adult Still disease in the world, T cell depletion, immunological resetting, T-reg ,NO ,autologous transplantation ,Refractory ,Prednisone ,Synovitis ,T-reg ,Humans ,Medicine ,Autologous transplantation ,autoimmune diseases ,Still disease ,Transplantation ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,immunological resetting ,Hematology ,medicine.disease ,Surgery ,Joint pain ,CD34 ,first tranplant in adult Still disease in the world ,medicine.symptom ,T cell depletion ,business ,Still's Disease, Adult-Onset ,medicine.drug - Abstract
We report a 38-year-old patient affected by refractory adult onset Still's disease who achieved a prolonged remission following CD34-selected ABMT. The conditioning regimen was based on the use of CY and anti-thymocyte globulin. A 3.0 and 2.0 log reduction of T (CD3+) and B (CD19+) lymphocytes, respectively, was obtained using a Ceprate device to select CD34+ cells from PBSC. In the pre-transplant period (1994-1998) the patient had a chronic persistent disease course with frequent and recurrent systemic articular flares and loss of some functional abilities, despite daily prednisone, pulses of CY and immunosuppressive therapy (CYA or MTX). At the time of ABMT the patient had become non-ambulatory. Within 3 weeks of ABMT the patient showed a marked decrease in joint swelling, and morning stiffness. Joint pain and systemic symptoms disappeared, the patient was able to walk and run and gained general well being. ESR, C-reactive protein and WBC count were significantly decreased, while Hb level increased. This partial remission persisted for at least 1 year after ABMT, although at 15 months of follow-up a reappearance of moderate synovitis in the knees and wrists was noted. Our data further showed that both patient BM microenvironment and stem-progenitor cell function (as assessed by LTC-IC assay) were damaged even 1 year after CD34-selected ABMT, suggesting that the persistence of these alterations could have facilitated the favorable outcome of the disease following ABMT. Bone Marrow Transplantation (2000) 25, 1307-1310.
- Published
- 2000
39. CXCR-4 Expression on Bone Marrow CD34+ Cells Prior to Mobilization Can Predict Mobilization Adequacy in Patients with Hematologic Malignancies.
- Author
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Melissa Dabusti, Francesco Lanza, Diana Campioni, Barbara Castagnari, Alessia Tieghi, Sabrina Moretti, Marina Punturieri, Cristiano De Angeli, Romedio Spanedda, Eros Ferrazzi, and Gianluigi Castoldi
- Published
- 2003
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