25 results on '"Maria Paola Bianchi"'
Search Results
2. Arrhythmias and Cardiogenic Shock: A Rare Disease Presentation of Diffuse Large B-Cell Lymphoma with Cardiac Involvement
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Sabrina Mariani, Sabrina Pelliccia, Maria Paola Bianchi, Monica Piedimonte, Martina Bongiovanni, Marco Testa, Arianna Di Napoli, and Agostino Tafuri
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diffuse large B-cell lymphoma ,cardiac involvement ,fractionated chemotherapy ,Medicine - Abstract
Extranodal involvement of non-Hodgkin lymphoma (NHL) has been reported in 20–40% of patients and has been typically observed in the skin, bones, gastrointestinal tract, liver and brain. Cardiac involvement has been reported in up to 20% of autopsy cases of patients with NHL and accounts for about 2% of all cardiac malignancies. Here, we report a peculiar case of a secondary cardiac diffuse large B-cell lymphoma (DLBCL), occurring with an abrupt hemodynamic instability, characterized by a sudden ventricular tachycardia and cardiogenic shock. The patient promptly started the first cycle of chemotherapy and was admitted to the cardiac intensive care unit (CICU) of our institution to prevent potential cardiovascular complications during treatment. We applied a fractionated treatment approach, progressively reaching standard doses, to decrease the risk of early death and ensure a successful management.
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- 2021
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3. A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review
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Monica Piedimonte, Tiziana Ottone, Valentina Alfonso, Antonella Ferrari, Esmeralda Conte, Mariadomenica Divona, Maria Paola Bianchi, Maria Rosaria Ricciardi, Simone Mirabilii, Roberto Licchetta, Alessia Campagna, Laura Cicconi, Giulia Galassi, Sabrina Pelliccia, Annapaola Leporace, Francesco Lo Coco, and Agostino Tafuri
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Acute myeloid leukemia ,Philadelphia chromosome ,BCR-ABL1 e6a2 ,Atypical transcripts ,TKI ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Philadelphia (Ph) chromosome results from the reciprocal translocation t(9;22)(q34.1;q11.2) and is diagnostic for chronic myeloid leukemia (CML). However, this translocation is also found in acute lymphoid leukemia (ALL), as well as in rare cases of acute myeloid leukemias (AML). Most patients with CML harbor either the e13a2 or the e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. Moreover, several atypical BCR-ABL1 transcripts, beside the most common e1a2, e13a2 and e14a2, have been described, mainly in patients with CML. However, ALL and de novo AML may also carry BCR-ABL1 atypical transcripts which will confer a poor prognosis. Case presentation A 78-years old male was admitted at our hospital with clinical and laboratory features allowing to make the diagnosis of AML. No evidence of a preceding CML (splenomegaly or basophilia) was found. The karyotype on G-banded metaphases was 46,XY, t(9;22)(q34;q11). While the molecular analysis was ongoing, the patient started treatment based on hydroxyurea followed by 5-aza-2′-deoxycytidine. The molecular biology analysis revealed the simultaneous presence of the common p190 e1a2 and the rare e6a2 isoforms. Because of persistent pancytopenia and presence of blasts, according to the molecular data, he was then switched to tyrosine kinase inhibitors (TKIs) treatment. Nevertheless, after 2 months, the patient was still refractory to second line treatment dying because of a pulmonary infection. Conclusion The atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR-ABL1 transcripts may help to establish optimal treatment approaches on these aggressive BCR-ABL1 phenotypes in different setting of patients.
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- 2019
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4. On the Size of Two-Way Reasonable Automata for the Liveness Problem.
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Maria Paola Bianchi, Juraj Hromkovic, and Ivan Kovác
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- 2018
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5. Online Minimum Spanning Tree with Advice.
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Maria Paola Bianchi, Hans-Joachim Böckenhauer, Tatjana Brülisauer, Dennis Komm, and Beatrice Palano
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- 2018
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6. Online Minimum Spanning Tree with Advice - (Extended Abstract).
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Maria Paola Bianchi, Hans-Joachim Böckenhauer, Tatjana Brülisauer, Dennis Komm, and Beatrice Palano
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- 2016
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7. Quantum finite automata: Advances on Bertoni's ideas.
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Maria Paola Bianchi, Carlo Mereghetti, and Beatrice Palano
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- 2017
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8. On the Size of Two-Way Reasonable Automata for the Liveness Problem.
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Maria Paola Bianchi, Juraj Hromkovic, and Ivan Kovác
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- 2015
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9. On the Power of One-Way Automata with Quantum and Classical States.
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Maria Paola Bianchi, Carlo Mereghetti, and Beatrice Palano
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- 2015
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10. Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients, with Diffuse Large B-Cell Lymphoma
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Guido Bocci, Sabrina Pelliccia, Paola Orlandi, Matteo Caridi, Marta Banchi, Gerardo Musuraca, Arianna Di Napoli, Maria Paola Bianchi, Caterina Patti, Paola Anticoli-Borza, Roberta Battistini, Ivana Casaroli, Tiziana Lanzolla, Agostino Tafuri, and Maria Christina Cox
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chemo-free ,metronomic chemotherapy ,DLBCL ,diffuse-large-b-cell-lymphoma ,elderly ,frail ,comprehensive geriatric assessment ,dlbcl ,General Medicine - Abstract
The upfront treatment of very elderly and frail patients with diffuse large B-cell lymphoma (DLBCL) is still a matter of debate. Herein, we report results of the metronomic all-oral DEVEC [prednisolone/deltacortene®, vinorelbine (VNR), etoposide (ETO), cyclophosphamide] combined with i.v. rituximab (R). This schedule was administered as a first line therapy in 22 elderly/frail DLBCL subjects (median age = 84.5 years). In 17/22 (77%) patients, the Elderly-IPI-score was high. After a median follow-up of 24 months, 15 patients had died: seven (50%) for causes unrelated to DLBCL or its treatment, six (40%) for progression, and two (13%) for multiorgan failure. Six treatment-pertinent serious-adverse-events occurred. At the end of induction, 14/22 (64%) achieved complete remission; overall survival and event-free survival at 24 months were both 54% (95% CI = 32–72%), while the time to progression was 74% (95% CI = 48–88%). Furthermore, antiproliferative and proapoptotic assays were performed on DLBCL/OCI-LY3 cell-line using metronomic VNR and ETO and their combination. Both metronomic VNR and ETO had concentration-dependent antiproliferative (IC50 = 0.036 ± 0.01 nM and 7.9 ± 3.6 nM, respectively), and proapoptotic activities in DLBCL cells. Co-administration of the two drugs showed a strong synergism (combination index < 1 and dose reduction index > 1) against cell proliferation and survival. This low-dose schedule seems to compare favourably with intravenous-CHEMO protocols used in the same subset. Indeed, the high synergism shown by metronomic VRN+ETO in in vitro studies, explains the remarkable clinical responses and it allows significant dose reductions.
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- 2022
11. Efficacy of Residual Site Radiation Therapy (ISRT) in Patients with Primary Mediastinal Lymphoma with Deauville Score 4 Following R-CHT: Results of a Retrospective Mono Institutional Study
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Giuseppe Facondo, Mattia Serio, Gianluca Vullo, Maria Paola Bianchi, Sabrina Pelliccia, Alice Di Rocco, Tiziana Lanzolla, Maurizio Valeriani, Arianna Di Napoli, Agostino Tafuri, Maurizio Martelli, Mattia Falchetto Osti, and Vitaliana De Sanctis
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lymphoma ,primary mediastinal lymphoma ,radiotherapy ,residual site radiation therapy ,General Medicine - Abstract
Background: In order to evaluate the efficacy of residual site radiation therapy (RSRT) in terms of progression-free survival (PFS) and overall survival (OS) in patients with primary mediastinal lymphoma (PMBCL) with Deauville Score 4 (DS 4) following rituximab and chemotherapy treatment (R-ICHT). Methods: Thirty-one patients with PMBCL were recruited. After completion of R-ICHT, patients were staged with 18F-fluorodeoxyglucose positron-emission tomography, showing DS 4, and were treated with adjuvant RSRT. The chosen techniques for RT delivery were intensity-modulated radiation therapy (IMRT) or three-dimensional conformal RT (3D-CRT). Most patients underwent the first one using cone-beam computed tomography (CBCT). All patients were evaluated every 3 months for the first 2 years and every 6 months afterwards for a period of at least 5 years, with clinical and radiological procedures as required. Results: All patients received RSRT with a dose of 30 Gy in 15 fractions. The median follow-up time of 52.7 months (IQR: 26–64.1 months). The 5-year OS rate was 100%. The 2-year and 5-year PFS rates were 96.7% and 92.5%, respectively. Patients with relapsed disease had been treated with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Conclusion: RSRT in patients with PMBCL treated with ICHT and DS 4 did not impact unfavorably on patient survival.
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- 2023
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12. Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly/FRAIL Patients, with Diffuse Large B-Cell Lymphoma
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M. Christina Cox, Sabrina Pelliccia, Paola Orlandi, Arianna Di Napoli, Gerardo Musuraca, Caterina Patti, Maria Paola Bianchi, Matteo Caridi, Marta Banchi, Roberta Battistini, Tiziana Lanzolla, Agostino Tafuri, and Guido Bocci
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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13. [18F]FDG PET/CT in Patients Affected by SARS-CoV-2 and Lymphoproliferative Disorders and Treated with Tocilizumab
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Alberto Signore, Chiara Lauri, Maria Paola Bianchi, Sabrina Pelliccia, Andrea Lenza, Simone Tetti, Maria Luisa Martini, Gabriele Franchi, Fabio Trapasso, Luciano De Biase, Antonio Aceti, and Agostino Tafuri
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Medicine (miscellaneous) - Abstract
Objectives: Interstitial pneumonia is a severe complication induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several treatments have been proposed alone or, more often, in combination, depending, also, on the presence of other organ disfunction. The most frequently related, well-described, and associated phenomenon is pan-lymphopenia with circulating, high levels of cytokines. We report, here, on two patients with COVID-19 and lymphoproliferative disorders treated with Tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor) and followed by an [18F]FDG PET/CT to early evaluate the therapy’s efficacy. Methods: One patient with angioimmunoblastic T-lymphoma (A), one with Hodgkin lymphoma (A), and both with positive RT-PCR for SARS-CoV-2 and with similar clinical findings of interstitial pneumonia at the CT scan, were imaged by [18F]FDG PET/CT before and 14 days after a single dose of Tocilizumab. Results: In both patients, the basal [18F]FDG PET/CT showed a diffused lung parenchyma uptake, corresponding to the hyperdense areas at the CT scan. After 2 weeks of a Tocilizumab infusion, patient B had an improvement of symptoms, with normalization of the [18F]FDG uptake. By contrast, patient A, who was still symptomatic, showed a persisting and abnormal distribution of [18F]FDG. Interestingly, both patients showed a low bone marrow uptake of [18F]FDG at the diagnosis and after 15 days, while the spleen uptake was low only in lymphopenic patient A; both are indirect signs of an immune deficiency. Conclusions: In conclusion, in these two patients, interstitial pneumonia was efficiently treated with Tocilizumab, as demonstrated by the [18F]FDG PET/CT. Our results confirm that interleukin-6 (IL6) has a role in the COVID-19 disease and that anti-cytokine treatment can also be performed in patients with lymphoproliferative disorders.
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- 2022
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14. Central nervous system immune reconstitution inflammatory syndrome after autologous stem cell transplantation
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Giusy Antolino, Simone Mirabilii, Maria Rosaria Ricciardi, Giacinto La Verde, Antonella Ferrari, Valentina Gianfelici, Maria Paola Bianchi, Alessia Campagna, Raffaele Iorio, Monica Piedimonte, Giorgio Tasca, Agostino Tafuri, Sabrina Pelliccia, Giulia Galassi, and Esmeralda Conte
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Central Nervous System ,Transplantation ,business.industry ,Central nervous system ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Transplantation, Autologous ,myeloma ,Autologous stem-cell transplantation ,medicine.anatomical_structure ,asct ,Immune reconstitution inflammatory syndrome ,Immune Reconstitution Inflammatory Syndrome ,Immunology ,iris ,medicine ,Humans ,Transplantation, Homologous ,business - Published
- 2019
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15. IBRUTINIB IN PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA: REAL LIFE DATA FROM THE 'RETE EMATOLOGICA DEL LAZIO PER I LINFOMI' (RELLI)
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Fulvia Fanelli, A. Di Rocco, Elena Papa, Luigi Petrucci, Gabriella Tomei, Maria Cantonetti, Francesca Palombi, Agostino Tafuri, Cristiano Tesei, Livio Pupo, Alessandro Andriani, Roberta Battistini, S Hoaus, S Mariani, Elena Maiolo, Sabrina Pelliccia, and Maria Paola Bianchi
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Real life data ,chemistry.chemical_compound ,chemistry ,Ibrutinib ,Internal medicine ,Relapsed refractory ,medicine ,In patient ,Mantle cell lymphoma ,business - Published
- 2021
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16. Clinical utility and physician perceptions of a digital platform for electronic patient-reported outcomes monitoring in patients with hematologic malignancies in real-world practice
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Edoardo La Sala, Massimo Breccia, Davide Giusti, Andrea Patriarca, Claudio Cartoni, Francesca Fazio, Elisabetta Lugli, Francesco Cottone, Elisabetta Colaci, Giovanni Caocci, Esmeralda Conte, Marco Vignetti, Claudio Fozza, Caterina Patti, Giusy Antolino, Ombretta Annibali, Paolo de Fabritiis, Nicolina Rita Ardu, Luigi Rigacci, Leonardo Potenza, Valeria Pioli, Salvatrice Mancuso, Sergio Siragusa, Michelina Santopietro, Isabella Capodanno, Mario Luppi, Massimo Pini, Paola Fazi, Maria Paola Bianchi, Agostino Tafuri, Ida Carmosino, Maria Teresa Petrucci, Pasquale Niscola, Marco Santoro, Alice Di Rocco, Fulvia Fanelli, and Fabio Efficace
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medicine.medical_specialty ,business.industry ,Family medicine ,Immunology ,Physician perception ,Medicine ,In patient ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
Background There is now great interest in using digital health tools to monitor patients' health status in real-world practice. Such tools often include electronic-patient-reported outcome (ePRO) systems in which symptoms questions are included into online interfaces for patient self-reporting, with real-time alerts triggered to the treating physician if severe symptoms or problems are reported. However, there is little information about the clinical utility and user perceptions of these systems, and this is particularly true in the area of hematology. Objectives This study investigates physicians' perceptions of usability and clinical utility of using remote ePROs in routine practice of patients with hematologic malignancies and explored implications in the delivery of patient care. Patients and Methods Remote ePROs are being gathered since December 2020 by the ALLIANCE Digital Health Platform, whose details of the development process have been previously described (Efficace F. et al., JMIR Res Protoc. 2021 Jun 1;10:e25271). Adult patients diagnosed with any hematologic malignancy are eligible to enter the platform, after having provided written informed consent. Aspects related to health-related quality of life (HRQoL), symptoms and medication adherence are assessed via validated PRO measures. The platform allows for real-time graphical presentation to physicians of individual patient symptoms and HRQoL outcomes. Based on a pre-defined algorithm, which includes the presence of clinically important problems and symptoms, the platform triggers automated alerts to the treating haematologists and medical staff. The definition of clinically important problems and symptoms is based on previously defined evidence-based thresholds (Giesinger J. et al., J Clin Epidemiol. 2020 Feb;118:1-8). We asked treating haematologists a feedback about their experience in using the platform, by an ad hoc web-survey consisting of 27 items covering several domains, including: usability and benefits, current use, evaluation of patient health-status, symptoms and adverse events, as well as physician-patient communication. We summarized characteristics of enrolled patients and treating haematologists by proportions, mean, median and range. We also used logistic regression analysis to check the possible association of characteristics of haematologists with survey results. Results Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) accepted to enter the ALLIANCE platform, currently activated in 19 centers. The median age of patients was 57 years (range 21-91) and 58% were males. The majority were diagnosed with chronic myeloid leukemia (n=32, 18%) and multiple myeloma (n=31, 17%) and were in stable disease (n=89, 49%). Twenty-three hematologists (44% males) with a median age of 42 years (range 31-63) and an average 17 years (range 5-34) of experience in clinical practice, completed the survey. The majority of physicians (78%) accessed the platform at least once per month (of whom 39% at least once per week), regardless the alerts sent by the system about patients' clinically relevant problems. The frequency of access on a regular basis was also independent of physician sex (p=0.393) and years of experience in clinical practice (p=0.404). Overall, 57% of hematologists discussed often or very often ePROs with their patients, while 83% and 61% deemed this information helpful to better identify symptomatic adverse events (AEs) of grade 1-2 or of grade 3-4, respectively (see figure). Also, 87% and 91% of hematologists found ePROs useful to improve physician-patient communication and the accuracy of documentation of symptomatic AEs (regardless of severity), respectively. Physicians' responses to selected items of the survey are reported in the figure. Conclusions: Current findings support the clinical utility, from the perspective of the treating physician, of integrating ePROs into routine cancer care of patients with hematologic malignancies. Figure 1 Figure 1. Disclosures Efficace: Takeda: Consultancy; Janssen: Consultancy; Abbvie: Consultancy, Other: Grants (to Institution); Amgen: Consultancy, Other: Grants (to Institution). Breccia: Bristol Myers Squibb/Celgene: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Fazio: Janseen: Honoraria. Petrucci: Karyopharm: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board. Rigacci: Merck: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tafuri: Roche: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Siragusa: Novartis, CSL, Behring, Amgen, Novonoridsk, SOBI, Bayer: Consultancy, Honoraria, Speakers Bureau. Patriarca: Incyte: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Argenix: Honoraria. Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Vignetti: Novartis: Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria.
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- 2021
17. Online Minimum Spanning Tree with Advice
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Dennis Komm, Beatrice Palano, Tatjana Brülisauer, Maria Paola Bianchi, and Hans-Joachim Böckenhauer
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Discrete mathematics ,Computer science ,Online algorithm ,Advice complexity ,Online minimum spanning tree problem ,0102 computer and information sciences ,02 engineering and technology ,Strength of a graph ,Minimum spanning tree ,01 natural sciences ,Graph ,Vertex (geometry) ,Combinatorics ,Circulant graph ,Kruskal's algorithm ,010201 computation theory & mathematics ,020204 information systems ,Reverse-delete algorithm ,0202 electrical engineering, electronic engineering, information engineering ,Computer Science (miscellaneous) ,Regular graph ,Feedback vertex set ,Graph factorization ,Advice (complexity) ,Mathematics ,MathematicsofComputing_DISCRETEMATHEMATICS - Abstract
In the online minimum spanning tree problem, a graph is revealed vertex by vertex; together with every vertex, all edges to vertices that are already known are given, and an online algorithm must irrevocably choose a subset of them as a part of its solution. The advice complexity of an online problem is a means to quantify the information that needs to be extracted from the input to achieve good results. For a graph of size [Formula: see text], we show an asymptotically tight bound of [Formula: see text] on the number of advice bits to produce an optimal solution for any given graph. For particular graph classes, e.g., with bounded degree or a restricted edge weight function, we prove that the upper bound can be drastically reduced; e.g., [Formula: see text] advice bits allow to compute an optimal result if the weight function equals the Euclidean distance; if the graph is complete and has two different edge weights, even a logarithmic number suffices. Some of these results make use of the optimality of Kruskal’s algorithm for the offline setting. We also study the trade-off between the number of advice bits and the achievable competitive ratio. To this end, we perform a reduction from another online problem to obtain a linear lower bound on the advice complexity for any near-optimal solution. Using our results finally allows us to give a lower bound on the expected competitive ratio of any randomized online algorithm for the problem, even on graphs with three different edge weights.
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- 2018
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18. Quantum finite automata: Advances on Bertoni's ideas
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Beatrice Palano, Carlo Mereghetti, and Maria Paola Bianchi
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TheoryofComputation_COMPUTATIONBYABSTRACTDEVICES ,Theoretical computer science ,Finite-state machine ,Nested word ,General Computer Science ,0102 computer and information sciences ,02 engineering and technology ,ω-automaton ,Nonlinear Sciences::Cellular Automata and Lattice Gases ,01 natural sciences ,Theoretical Computer Science ,Algebra ,TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES ,Deterministic finite automaton ,010201 computation theory & mathematics ,0202 electrical engineering, electronic engineering, information engineering ,Automata theory ,Quantum finite automata ,020201 artificial intelligence & image processing ,Nondeterministic finite automaton ,Computer Science::Formal Languages and Automata Theory ,Quantum cellular automaton ,Mathematics - Abstract
We first outline main steps and achievements along Bertoni's research path in quantum finite automata theory from the very basic definitions of the models of quantum finite automata throughout the investigation of their computational and descriptional power. Next, we choose to focus on Bertoni's studies on quantum finite automata descriptional complexity. In particular, we expand on a statistical framework for the synthesis of succinct quantum finite automata, discussing its adaptation to the case of multiperiodic events and languages. We then improve such a framework to obtain even more succinct quantum finite automata for some multiperiodic languages. Finally, we introduce some promise problems for multiperiodic inputs, showing that even on this class of problems the descriptional power of quantum finite automata greatly outperforms that of equivalent classical finite automata. We build small size Monte Carlo quantum finite automata for multiperiodic languages.We analyze the modular architecture of such Monte Carlo quantum finite automata.We solve promise problems on multiperiodic inputs by small quantum finite automata.
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- 2017
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19. On the Size of Two-Way Reasonable Automata for the Liveness Problem
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Ivan Kováč, Juraj Hromkovič, and Maria Paola Bianchi
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Discrete mathematics ,Theoretical computer science ,Computer science ,Liveness ,Timed automaton ,0102 computer and information sciences ,02 engineering and technology ,ω-automaton ,01 natural sciences ,Automaton ,Nondeterministic algorithm ,Two-way finite automata ,descriptional complexity ,nondeterminism vs. determinism ,Deterministic finite automaton ,010201 computation theory & mathematics ,Deterministic automaton ,0202 electrical engineering, electronic engineering, information engineering ,Computer Science (miscellaneous) ,Quantum finite automata ,Automata theory ,020201 artificial intelligence & image processing ,Two-way deterministic finite automaton ,Nondeterministic finite automaton ,Computer Science::Formal Languages and Automata Theory ,Mathematics - Abstract
The existence of a substantial gap between deterministic and nondeterministic two-way automata is one of the most famous open problems in automata theory. This problem is also related to the fundamental DLOG vs. NLOG question. An exponential gap between the number of states of two-way nondeterministic automata (2NFAS) and their deterministic counterparts (2DFAS) has been proved only for some restrictions of 2DFAS up to now. It seems that the hardness of this problem lies in the fact that, when trying to prove lower bounds, we must consider every possible automaton, without imposing any particular structure or meaning to the states, while when designing a specific automaton, we always assign an unambiguous interpretation to the states. In an attempt to capture the concept of meaning of states, a new model of two-way automata, namely reasonable automaton (RA), was introduced in [6]. In a RA, each state is associated with a logical formula expressing some properties of the input word, and transitions are designed to maintain consistency within this setting. In this paper we extend the study, started in [6], of the descriptional complexity of RAS solving the liveness problem, showing several lower and upper bounds with respect to the logic used for describing the meaning of the individual states. ISSN:0129-0541 ISSN:1793-6373
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- 2018
20. Italian real life experience with brentuximab vedotin: results of a large observational study on 234 relapsed/refractory Hodgkin's lymphoma
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Vittorio Stefoni, Vincenzo Pavone, Lisa Argnani, Alessandra Romano, Michele Merli, Pier Luigi Zinzani, Amalia De Renzo, Pellegrino Musto, Gian Matteo Rigolin, Maria Goldaniga, Luigi Rigacci, Monica Tani, Donato Mannina, Michele Spina, Angelo Michele Carella, Anna Marina Liberati, Armando Santoro, Alessandro Pulsoni, Patrizio Mazza, Corrado Schiavotto, Livio Trentin, Chiara Rusconi, Anna Vanazzi, Caterina Patti, Stefan Hoaus, Stefano Molica, Stefano Volpetti, Guido Gini, Maurizio Bonfichi, Maria Paola Bianchi, Paolo Corradini, Antonello Pinto, Alessandro Broccoli, Patrizia Tosi, Fioravante Ronconi, Filippo Gherlinzoni, Barbara Botto, Giuseppe Gritti, Daniele Vallisa, Cinzia Pellegrini, Francesco Gaudio, Angelo Fama, Pellegrini, Cinzia, Broccoli, Alessandro, Pulsoni, Alessandro, Rigacci, Luigi, Patti, Caterina, Gini, Guido, Mannina, Donato, Tani, Monica, Rusconi, Chiara, Romano, Alessandra, Vanazzi, Anna, Botto, Barbara, Santoro, Armando, Hoaus, Stefan, Rigolin, Gian Matteo, Musto, Pellegrino, Mazza, Patrizio, Molica, Stefano, Corradini, Paolo, Fama, Angelo, Gaudio, Francesco, Merli, Michele, Ronconi, Fioravante, Gritti, Giuseppe, Vallisa, Daniele, Tosi, Patrizia, Liberati, Anna Marina, Pinto, Antonello, Pavone, Vincenzo, Gherlinzoni, Filippo, Bianchi, Maria Paola, Volpetti, Stefano, Trentin, Livio, Goldaniga, Maria Cecilia, Bonfichi, Maurizio, De Renzo, Amalia, Schiavotto, Corrado, Spina, Michele, Carella, Angelo Michele, Stefoni, Vittorio, Argnani, Lisa, and Zinzani, Pier Luigi
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Oncology ,medicine.medical_specialty ,Hodgkin’s lymphoma ,Context (language use) ,Neutropenia ,stem cell transplantation ,NO ,Efficacy ,03 medical and health sciences ,0302 clinical medicine ,brentuximab vedotin ,real life ,Internal medicine ,medicine ,long-term response ,Progression-free survival ,Brentuximab vedotin ,Hodgkin's lymphoma ,business.industry ,Retrospective cohort study ,medicine.disease ,Clinical trial ,Long-term response ,Real life ,Stem cell transplantation ,030220 oncology & carcinogenesis ,Clinical Research Paper ,business ,030215 immunology ,medicine.drug - Abstract
A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. Duration of response did not differ for who achieved at least PR and then either did or did not undergo consolidative transplant. Overall, the treatment was well tolerated and no death has been linked to BV-induced toxicity. Our report confirms activity in elderly patients, duration of response unrelated to the consolidation with transplant procedure, the relevance of the CR status at first restaging, and the role of BV as a bridge to transplant for chemorefractory patients.
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- 2017
21. Biological Aspects of mTOR in Leukemia
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Valentina Gianfelici, Agostino Tafuri, Maria Paola Bianchi, Monica Piedimonte, Simone Mirabilii, and Maria Rosaria Ricciardi
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0301 basic medicine ,mTOR inhibitors ,Cell signaling ,Review ,computer science applications1707 computer vision and pattern recognition ,Biology ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,03 medical and health sciences ,microRNA ,medicine ,Extracellular ,Animals ,Humans ,cell signaling ,RNA, Neoplasm ,Physical and Theoretical Chemistry ,Protein Kinase Inhibitors ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,PI3K/AKT/mTOR pathway ,miRNA ,TOR Serine-Threonine Kinases ,apoptosis ,leukemia ,metabolism ,mirna ,mtor inhibitors ,catalysis ,molecular biology ,spectroscopy ,physical and theoretical chemistry ,organic chemistry ,inorganic chemistry ,Organic Chemistry ,General Medicine ,medicine.disease ,Discovery and development of mTOR inhibitors ,Neoplasm Proteins ,Computer Science Applications ,MicroRNAs ,Leukemia ,Cell Transformation, Neoplastic ,030104 developmental biology ,Cell metabolism ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cancer research - Abstract
The mammalian target of rapamycin (mTOR) is a central processor of intra- and extracellular signals, regulating many fundamental cellular processes such as metabolism, growth, proliferation, and survival. Strong evidences have indicated that mTOR dysregulation is deeply implicated in leukemogenesis. This has led to growing interest in the development of modulators of its activity for leukemia treatment. This review intends to provide an outline of the principal biological and molecular functions of mTOR. We summarize the current understanding of how mTOR interacts with microRNAs, with components of cell metabolism, and with controllers of apoptotic machinery. Lastly, from a clinical/translational perspective, we recapitulate the therapeutic results in leukemia, obtained by using mTOR inhibitors as single agents and in combination with other compounds.
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- 2018
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22. Targeting Glycolysis and MAPK Pathway: A Combined Pre-Clinical Approach on Acute Myeloid Leukemia
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Agostino Tafuri, Maria Paola Bianchi, Maria Rosaria Ricciardi, Simone Mirabilii, Roberto Licchetta, and Monica Piedimonte
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MAPK/ERK pathway ,Chemistry ,Immunology ,Pyruvate Dehydrogenase (Lipoamide) ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,Cell culture ,Precursor cell ,Cancer research ,Glycolysis ,Annexin A5 ,Phosphotransferases - Abstract
We have demonstrated that selective MEK inhibitors (MEK-I) significantly inhibit in vitro the growth of AML cell lines and primary AML blasts (Ricciardi et al., JMM 2012). However, these effects were mostly related to the inhibition of cell cycle progression, while apoptosis induction requires higher concentrations of the inhibitor and longer times of exposure. Among the many downstream effectors of MAPK pathway, metabolism is one of the key aspects that can be targeted at several levels for therapeutic perspectives (Ricciardi et al., Blood 2015). In this study, we have explored on AML cells the functional effects of combining the MEK1/2 inhibitor, PD0325901 (PD), with a metabolic modulator, dichloroacetate (DCA), which acts as pyruvate dehydrogenase kinase (PDHK) inhibitor. AML cell lines (OCI-AML3, U937, MOLM13, HL60) and AML primary samples were exposed to PD (2.5-1000nM) and DCA (0.5-2mM), alone or in combination. PD dose-dependently inhibited cell growth of OCI-AML3, HL60 and MOLM13, showing a constitutive activation of RAS/RAF/MEK/ERK pathway. This activation was not seen in U937, thus exhibiting resistance to PD. DCA shows a pro-apoptotic activity on AML cells, only at the highest concentration. The combination between PD and DCA synergistically enhanced the antiproliferative effect, with a combination index (CI) ranging between 0.37 and 0.41 in OCI-AML3, as measured by isobologram analysis from MTT data. Conversely, in U937 the combination resulted antagonistic. Co-administration of non- or sub-toxic concentrations of DCA (2mM) and of PD (10nM) resulted in a strong increase of cell death in OCI-AML3 (Annexin V). The PD/DCA combination significantly increased Annexin V+ cells, at 72 hours, (65.7±25.0%), compared to single compounds: 16.4±8.7% with 10nM PD (p=0.03) and 28.0±12.4% with 2mM DCA (p=0.04). Similar results were obtained in HL60 and MOLM13 (data not shown). In the U937 cell line, resistant to PD, the levels of apoptosis observed with DCA alone were not further enhanced by the combination: 6.19±1.7% (1000nM PD), 23.63±6.7% (2mM DCA), 31.28±9.9% (PD/DCA). At a protein level, densitometric analysis of Western blot carried out on OCI-AML3 demonstrated that PD/DCA was able to further increase PD-induced ERK inhibition (from 40% to 54%), while DCA alone, as expected, had no effect. Real time metabolic data, obtained by a Seahorse XF24 on OCI-AML3, showed that the combination of PD and DCA affected mitochondrial metabolism: basal respiration and ATP production were impaired by 37.34±10.4% (p=0.012) and by 56.31±10.0% (p=0.003), respectively, compared to control. On the other hand, both maximal respiration and spare respiratory capacity were increased by 28.80±9.5% (p=0.025) and 68.78±14.2% (p These preliminary results suggest that the combination of a signal transduction and a metabolic inhibitor spares mitochondrial machinery while impairing at the same time its activity, thus resulting in an enhanced antiproliferative and pro-apoptotic effect on AML cells. Disclosures No relevant conflicts of interest to declare.
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- 2016
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23. The Neutrophil/Lymphocyte Ratio (N/L) Is a Prognostic Marker in Patients with Diffuse Large B Cell Lymphoma: A Prospective Study from the Lazio Lymphoma Registry
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Elena Maiolo, Cristiano Tesei, Marco Montanaro, Eleonora Alma, Livio Pupo, Roberta Battistini, Giuseppe Cimino, Virginia Naso, Anna Marina Liberati, Valerio Zoli, Federico De Angelis, Maria Paola Bianchi, Giuliana Rizzuto, Valeria Tomarchio, Maria Cantonetti, Francesca Palombi, Maria Chiara Tisi, Michela Ansuinelli, Elisabetta Abruzzese, Ombretta Annibali, Paola Anticoli Borza, Stefan Hohaus, and Maria Christina Cox
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Vincristine ,medicine.medical_specialty ,Pathology ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Lymphoma ,International Prognostic Index ,B symptoms ,Median follow-up ,Internal medicine ,medicine ,Absolute neutrophil count ,Rituximab ,medicine.symptom ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
The neutrophil/lymphocyte ratio (N/L) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. An increase in the neutrophil count is a marker of inflammation which is an essential part of the neoplastic process. Conversely, a decrease of the peripheral lymphocyte count might reflect an impairment of the host defense mechanism associated with advanced and aggressive cancers. Since There are only few reports on the N/L ratio in non-Hodgkin lymphomas. We studied the prognostic role of the N/L ratio at diagnosis in 286 patients with diffuse-large-B-cell lymphoma (DLBCL) enrolled in a multicenter prospective registry of the Lazio region in Italy The median age at diagnosis was 69 years (27-91) and the female/male ratio was:141/145.First, we analyzed for associations between N/L ratio and patient characteristics. The optimal cut-off value for the N/L was obtained using the Receiver Operating Curve (ROC) and according to the published data in solid tumor. N/L ≥ 4 was significantly associated with presence of B-symptoms (p=0.01) and elevated LDH levels (p=0.007) at diagnosis. Most patients were treated with R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) or R-CHOP-like (90%). Complete Remission (CR) + Partial Remission (PR) were obtained in 210/286 (73%). The median follow up period was 15 months (range: 1-33 months): 27 patients died for lymphoma relapse/progression and 16 for other causes. Patients with N/L ≥ 4 experienced a higher rate of relapse, while N/L< 4 was associated to a significantly better Overall (OS, P < 0.05) and Event Free Survival (EFS, P< 0.01). (Figure 1, panel a and b).Furthermore, considering only patients with IPI score ≤ 3, those with N/L Conclusion: The N/L ratio may be a useful and unexpensive prognostic marker in patients with DLBCL. The inferior outcome observed in patients with N/L ≥ 4 might reflect an immune and inflammatory imbalance induced by a more aggressive tumor, releasing directly or indirectly inflammatory cytokines and/or inducing immune suppression or exhaustion. A link with inflammation is suggested by the correlation of N/L ratio ≥ 4 with high LDH levels and the presence of B symptoms. Figure 1. Panel A. Overall Survival (OS) and Panel B. Event Free Survival (EFS) by N/L ratio. Panel C. Overall Survival (OS) by N/L in patients with IPI score ≤ 3. Table 1.Baseline patients characteristics (N = 268) and compared by N/L < 4 or ≥ 4 by using Chi-Square Test for categorical variables. Abbreviations not included in the text: IPI = International Prognostic Index; LDH = lactate dehydrogenase, PD: Progression Disease, NA: Not Applicable. Disclosures Cimino: Celgene: Honoraria; Bristol-Mayer: Honoraria.
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- 2016
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24. Metronomic Chemotherapy Is Effective and Well Tolerated in Relapsed/Refractory Elderly Patients with Aggressive B- and T-Cell Lymphomas
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Marco di Girolamo, Raffaele Porrini, Virginia Naso, Francesca di Landro, Elena Cavalieri, Daniela Prosperi, Agostino Tafuri, Maria Paola Bianchi, and Maria Christina Cox
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Oncology ,medicine.medical_specialty ,Performance status ,business.industry ,Immunology ,Follicular lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Metronomic Chemotherapy ,Surgery ,Regimen ,Prednisone ,Internal medicine ,medicine ,Rituximab ,Progression-free survival ,business ,Etoposide ,medicine.drug - Abstract
BACKGROUND: Elderly patients with Relapsed/Refractory (R/R) aggressive Large B-cell lymphoma (LBCL) and Peripheral T-cell lymphomas (PTCL), are commonly treated with intravenous conventional chemotherapies, which are often poorly tolerated and of short-lasting efficacy. Therefore only few fit-elderly patients might undergo intensive treatments with curative intent. Metronomic chemoterapy (MTN-CHT) is a new way of administering old drugs at low doses with only short chemotherapy free intervals. MTN-CHT may be combined with new targeted molecules, immunotherapies and radiotherapy. Although very few reports on MTN-CHT in LBCL and PTCL have been published existing data suggest that these lymphomas might respond to this approach. AIM: We aimed at demonstrating the efficacy and safety of MTN-CHT in a retrospective series of elderly patients with LBCL and PTCL, unfit for conventional treatments. PATIENTS AND TREATMENTS: From October 2008 up to May 2015 we treated elderly patients with R/R LBCL, Follicular Lymphoma(FL) and PTCL with MTN-CHT based regimen. Eligible patients should have given written informed consent, have a Performance Status=0-3, a life expection >2 months, be able to take oral therapy and have a care-giver. We used three different MTN schedules: 1] Provecip; 2] Vinblastine+Endoxan+Etoposide+Prednisone (VEED) and in the last two years an all-oral schedule 3] Navelbine+Endoxan+Etoposide+Prednisone (DE-VEC). All three schedules of MTN-CHT consisted of an induction phase of six months followed by a maintenance phase administered until progression or excessive toxicity. Rituximab was added to the induction phase for those patients characterized by CD20 expression. Thrombosis prophylaxis was carried out with aspirin or LMWH. RESULTS Patients features: LBCL=21; PTCL=7, FL=3; Age=77y (median, range 62-90), Previous CHT=2 (median, range 0-5) refractory to last CHT= 43%. MTN-CHT: 8 pts were treated with schedule 1], 8 pts with schedule 2] and 15 pts with schedule 3]. Outcome: in aggressive B and T-cell lymphomas (n=28pts) with all schedules Overall Response Rate = 62%, Complete Remission rate = 36%; Progression Free Survival = 8 months, Median Duration of Response (DOR)= 10 months. Overall Response Rate and Complete Remission in the subset treated with the all-oral DE-VEC schedule were 66% and 50% respectively. Serious adverse events: Extra hematologic toxicity grade 3-4: pulmonary embolism in 1pts; hematological toxicity of grade 3-4 and/or neutropenic infections in 6 patients 5 of whom had >2 previous conventional chemotherapies. The use of DE-VEC all-oral schedule reduced the number and the durations of day-hospital admissions. CONCLUSION Although our series is limited, these results suggest that MTN-CHT in elderly patients with R/R LBCL, PTCL and FL might achieve favorable results in terms of activity, toxicity and costs due to hospital admissions. With MTN-CHT most of the patients did not need G-CSF. Notably, patients who had had >2 lines of chemotherapies may be at very high risk of prolonged cytopenia and infections during MTN-CHT. Since the all-oral DE-VEC schedule was particularly manageable and active we believe that this combination deserve further investigation in aggressive lymphomas. Disclosures No relevant conflicts of interest to declare.
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- 2015
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25. Diagnostic Value of Minor Salivary Glands Biopsy in Systemic Amyloidosis
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Giulia Galassi, Agostino Tafuri, Armando Bartolazzi, Giusy Antolino, Maria Paola Bianchi, Francescaromana Festuccia, Giorgio Bandiera, Giacinto La Verde, and Paolo Menè
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Immunology ,Perforation (oil well) ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,Hematoma ,Biopsy Site ,Biopsy ,AL amyloidosis ,medicine ,Renal biopsy ,business ,Multiple myeloma - Abstract
Amyloidosis is a potentially fatal condition characterized by deposition of extracellular protein in an abnormal fibrillary form with a β-sheet structure, named amyloid, in several organs, especially in heart, kidney and liver. The tissue biopsy, stained with Congo red and demonstrating amyloid deposits with apple-green birefringence, is required for diagnosis. The biopsy of visceral organs is characterized by higher sensitivity although it requires invasive procedures bearing higher risk of complications, such as bleeding, hematoma and perforation. Therefore, fine-needle abdominal fat aspiration is the most common biopsy site. More recently an additional procedure has been performed and is at this time is under evaluation, being represented by minor salivary labial glands biopsy (MSGB) which is characterized by easy accessibility, low complication rate, and lower costs. Reliability of this procedure is under evaluation. We have analyzed all patients referred at our institution between March 2006 and April 2015, with the clinical or laboratory symptoms suggestive for amyloidosis (proteinuria, renal impairment, neuropathy and restrictive cardiomyopathy). In the first three years we performed biopsy by abdominal fat aspiration as first diagnostic step. Patients failing to obtain diagnostic material underwent a second biopsy, including surgical approaches. In order to minimize the use of invasive procedures, we have introduced MSGB, obtained by a small incision inside the lower lip. The sample was then collected and fixed in formalin, stained with Congo red and analyzed by polarized light microscopy. Immunohistochemical examination was performed whenever indicated to discriminate AA and AL amyloidosis. In our retrospective study we have examined results of MSGB from 44 patients during the time period between January 2008 and April 2015. All patient were affected with AL amyloidosis and 51% of them was associated with multiple myeloma. The deposits were characterized as AL λ in 80% of the patients and AL κ in 20%. The median age was 65 years (range 26-97), 30% were female and 70% male. In 38 patients (86%) the MSGB was positive, while in six (14%) was negative. Of these six patients, two presented localized amyloidosis (diagnosed by tongue and conjunctiva biopsy) and four underwent visceral organ biopsy (3 renal biopsies, 1 myocardial). MSGB is therefore a simple, safe, and reliable tool for the diagnosis of systemic amyloidosis. The advantages of MSGB include avoidance of more invasive methods, need for a small incision, quite a low risk of bleeding and nerve damage, applicability in the outpatient setting and rapid healing. In our experience, it was performed in all cases without adverse effects, demonstrating an overall diagnostic sensitivity of 86%. For this reason we introduce this procedure in our clinical practice. Disclosures No relevant conflicts of interest to declare.
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- 2015
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