266 results on '"Giuseppe Avvisati"'
Search Results
2. A novel scoring system for TIGIT expression in classic Hodgkin lymphoma
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Ombretta Annibali, Antonella Bianchi, Alba Grifoni, Valeria Tomarchio, Mariantonietta Tafuri, Martina Verri, Giuseppe Avvisati, and Anna Crescenzi
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Medicine ,Science - Abstract
Abstract Clinical use of immune-checkpoints inhibitors (anti PD-1/PD-L1) resulted very effective for the treatment of relapsed/refractory classic Hodgkin Lymphoma (CHL). Recently, T cell Ig and ITIM domains (TIGIT) has been recognized as an immune checkpoint receptor able to negatively regulate T cell functions. Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. TIGIT expression in T lymphocytes surrounding Hodgkin Reed-Sternberg (HRS) cells was observed in 19/34 patients (56%), of which 11 (58%) had advanced stages. In 16/19 (84%) cases, TIGIT+ peritumoral T lymphocytes showed also PD-1 expression. All 15 TIGIT− patients had PD-L1 expression in HRS cells (100%) while among 19 TIGIT+ patients, 11 (58%) were PD-L1+ and 8 (42%) were PD-L1−. Using a new scoring system for TIGIT immunoreactivity, all TIGIT+ cases with higher score (4/19) were PD-L1−. Our results confirm co-expression of TIGIT and PD-1 in peritumoral T lymphocytes. Of relevance, we demonstrated a mutually exclusive expression of TIGIT and PD-L1 using new TIGIT scoring system able to identify this immunocheckpoints’ modulation. These results pave the way to new therapeutic strategies for relapsed/refractory CHL.
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- 2021
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3. Emerging from the Darkness. Sudden Cardiac Death in Cardiac Amyloidosis
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Valeria Cammalleri, Valeria Maria De Luca, Giorgio Antonelli, Ombretta Annibali, Annunziata Nusca, Simona Mega, Myriam Carpenito, Danilo Ricciardi, Fiorella Gurrieri, Giuseppe Avvisati, Gian Paolo Ussia, and Francesco Grigioni
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implantable cardioverter defibrillator ,sudden cardiac death ,cardiac amyloidosis ,monoclonal immunoglobulin light chains ,transthyretin amyloidosis ,ventricular arrhythmia ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Cardiac amyloidosis (CA) manifests as infiltrative cardiomyopathy with a hypertrophic pattern, usually presenting with heart failure with a preserved ejection fraction. In addition, degenerative valvular heart disease, particularly severe aortic stenosis, is commonly seen in patients with CA. However, amyloid fibril deposition might also infiltrate the conduction system and promote the development of electrical disorders, including ventricular tachyarrhythmias, atrio-ventricular block or acute electromechanical dissociation. These manifestations can increase the risk of sudden cardiac death. This review summarises the pathophysiological mechanisms and risk factors for sudden cardiac death in CA and focuses on the major current concerns regarding medical and device management in this challenging scenario.
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- 2022
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4. A standardized flow cytometry network study for the assessment of circulating endothelial cell physiological ranges
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Paola Lanuti, Pasquale Simeone, Gianluca Rotta, Camillo Almici, Giuseppe Avvisati, Rosa Azzaro, Giuseppina Bologna, Alfredo Budillon, Melania Di Cerbo, Elena Di Gennaro, Maria Luisa Di Martino, Annamaria Diodato, Paolo Doretto, Eva Ercolino, Alessandra Falda, Chiara Gregorj, Alessandra Leone, Francesca Losa, Natalia Malara, Mirella Marini, Pasquale Mastroroberto, Vincenzo Mollace, Michele Morelli, Emma Muggianu, Giuseppe Musolino, Arabella Neva, Laura Pierdomenico, Silvia Pinna, Giovanna Piovani, Maria Serena Roca, Domenico Russo, Lorenza Scotti, Maria Cristina Tirindelli, Valentina Trunzo, Roberta Venturella, Carlo Vitagliano, Fulvio Zullo, Marco Marchisio, and Sebastiano Miscia
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Medicine ,Science - Abstract
Abstract Circulating endothelial cells (CEC) represent a restricted peripheral blood (PB) cell subpopulation with high potential diagnostic value in many endothelium-involving diseases. However, whereas the interest in CEC studies has grown, the standardization level of their detection has not. Here, we undertook the task to align CEC phenotypes and counts, by standardizing a novel flow cytometry approach, within a network of six laboratories. CEC were identified as alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in 269 healthy PB samples. Standardization was demonstrated by the achievement of low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of Median Fluorescence Intensity values of the most stable antigens that allowed CEC identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale = 11.55 CEC/mL). CEC count biological variability and method specificity were finally assessed. Results, obtained on a large population of donors, demonstrate that the established procedure might be adopted as standardized method for CEC analysis in clinical and in research settings, providing a CEC physiological baseline range, useful as starting point for their clinical monitoring in endothelial dysfunctions.
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- 2018
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5. A Curious Novel Combination of Nucleophosmin (NPM1) Gene Mutations Leading to Aberrant Cytoplasmic Dislocation of NPM1 in Acute Myeloid Leukemia (AML)
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Alessandra Venanzi, Roberta Rossi, Giovanni Martino, Ombretta Annibali, Giuseppe Avvisati, Maria Grazia Mameli, Paolo Sportoletti, Enrico Tiacci, Brunangelo Falini, and Maria Paola Martelli
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acute myeloid leukemia ,nucleophosmin ,NPM1 ,nuclear export signal (NES) ,exportin-1/XPO1 ,Genetics ,QH426-470 - Abstract
Nucleophosmin (NPM1) mutations occurring in acute myeloid leukemia (AML) (about 50 so far identified) cluster almost exclusively in exon 12 and lead to common changes at the NPM1 mutants C-terminus, i.e., loss of tryptophans 288 and 290 (or 290 alone) and creation of a new nuclear export signal (NES), at the bases of exportin-1(XPO1)-mediated aberrant cytoplasmic NPM1. Immunohistochemistry (IHC) detects cytoplasmic NPM1 and is predictive of the molecular alteration. Besides IHC and molecular sequencing, Western blotting (WB) with anti-NPM1 mutant specific antibodies is another approach to identify NPM1-mutated AML. Here, we show that among 382 AML cases with NPM1 exon 12 mutations, one was not recognized by WB, and describe the discovery of a novel combination of two mutations involving exon 12. This appeared as a conventional mutation A with the known TCTG nucleotides insertion/duplication accompanied by a second event (i.e., an 8-nucleotide deletion occurring 15 nucleotides downstream of the TCTG insertion), resulting in a new C-terminal protein sequence. Strikingly, the sequence included a functional NES ensuring cytoplasmic relocation of the new mutant supporting the role of cytoplasmic NPM1 as critical in AML leukemogenesis.
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- 2021
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6. CD123 Is Consistently Expressed on NPM1-Mutated AML Cells
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Vincenzo Maria Perriello, Ilaria Gionfriddo, Roberta Rossi, Francesca Milano, Federica Mezzasoma, Andrea Marra, Orietta Spinelli, Alessandro Rambaldi, Ombretta Annibali, Giuseppe Avvisati, Francesco Di Raimondo, Stefano Ascani, Brunangelo Falini, Maria Paola Martelli, and Lorenzo Brunetti
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acute myeloid leukemia (AML) ,CD123 ,NPM1 ,FLT3 ,immunotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
NPM1-mutated (NPM1mut) acute myeloid leukemia (AML) comprises about 30% of newly diagnosed AML in adults. Despite notable advances in the treatment of this frequent AML subtype, about 50% of NPM1mut AML patients treated with conventional treatment die due to disease progression. CD123 has been identified as potential target for immunotherapy in AML, and several anti-CD123 therapeutic approaches have been developed for AML resistant to conventional therapies. As this antigen has been previously reported to be expressed by NPM1mut cells, we performed a deep flow cytometry analysis of CD123 expression in a large cohort of NPM1mut and wild-type samples, examining the whole blastic population, as well as CD34+CD38− leukemic cells. We demonstrate that CD123 is highly expressed on NPM1mut cells, with particularly high expression levels showed by CD34+CD38− leukemic cells. Additionally, CD123 expression was further enhanced by FLT3 mutations, which frequently co-occur with NPM1 mutations. Our results identify NPM1-mutated and particularly NPM1/FLT3 double-mutated AML as disease subsets that may benefit from anti-CD123 targeted therapies.
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- 2021
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7. Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients.
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Ombretta Annibali, Livia Piccioni, Valeria Tomarchio, Erika Circhetta, Chiara Sarlo, Luca Franceschini, Maria Cantonetti, Emanuela Rizzo, Silvia Angeletti, Maria Cristina Tirindelli, Carolina Scagnolari, Maura Statzu, Giuseppe Avvisati, and Elisabetta Riva
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Medicine ,Science - Abstract
Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.
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- 2018
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8. In Situ Electrostimulation Drives a Regenerative Shift in the Zone of Infarcted Myocardium
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Cristiano Spadaccio, Alberto Rainer, Federico De Marco, Mario Lusini, Paolo Gallo, Pietro Sedati, Andrea Onetti Muda, Stefano De Porcellinis, Chiara Gregorj, Giuseppe Avvisati, Marcella Trombetta, Massimo Chello, Elvio Covino, David A. Bull, Amit N. Patel, and Jorge A. Genovese
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Medicine - Abstract
Electrostimulation represents a well-known trophic factor for different tissues. In vitro electrostimulation of non-stem and stem cells induces myogenic predifferentiation and may be a powerful tool to generate cells with the capacity to respond to local areas of injury. We evaluated the effects of in vivo electrostimulation on infarcted myocardium using a miniaturized multiparameter implantable stimulator in rats. Parameters of electrostimulation were organized to avoid a direct driving or pacing of native heart rhythm. Electrical stimuli were delivered for 14 days across the scar site. In situ electrostimulation used as a cell-free, cytokine-free stimulation system, improved myocardial function, and increased angiogenesis through endothelial progenitor cell migration and production of vascular endothelial growth factor (VEGF). In situ electrostimulation represents a novel means to stimulate repair of the heart and other organs, as well as to precondition tissues for treatment with cell-based therapies.
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- 2013
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9. HOW I TREAT NEWLY DIAGNOSED ACUTE PROMYELOCYTIC LEUKEMIA
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Giuseppe Avvisati
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Acute promyelocytic leukemia (APL) represents a medical emergency with a high rate of early mortality. As a consequence, as soon as the diagnosis is suspected based upon cytologic criteria, it is necessary to start all- trans retinoic acid (ATRA) treatment without delay. For patients with newly diagnosed APL, induction therapy with ATRA plus anthracycline based chemotherapy is recommended. At present the combination of arsenic trioxide plus ATRA should be considered for patients who are not candidates for anthracycline-based therapy. For pediatric and adult patients with APL aged < 60 years who achieve a CR with induction, I recommend 3 intensive courses of consolidation chemotherapy associated to ATRA , targeted on the basis of the risk group at diagnosis. In patients treated with a very intensive consolidation chemotherapy maintenance treatment can be omitted. However If a maintenance treatment has to be adopted I suggest the use of intermittent ATRA for 15 days every 3 months for a period of 2 years , rather than ATRA associated to chemotherapy. Moreover, taking into account the medical literature, a reduced dosage of ATRA ( 25 mg/m2) in pediatric patients and a consolidation chemotherapy of reduced intensity in elderly patients is recommended. Furthermore, in order to maximize survival, careful attention should be reserved to the coagulopathy and to the appearance of the differentiation syndrome . Finally, PCR for the PML/RARA fusion gene on a bone marrow specimen every three months for two years, and then every six months for additional three years are needed during the follow-up.
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- 2011
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10. Clinical and biological features of acute promyelocytic leukemia patients developing retinoic acid syndrome during induction treatment with all-trans retinoic acid and idarubicin
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Massimo Breccia, Roberto Latagliata, Ida Carmosino, Laura Cannella, Daniela Diverio, Anna Guarini, Maria Stefania De Propris, Maria Concetta Petti, Giuseppe Avvisati, Giuseppe Cimino, Franco Mandelli, and Francesco Lo-Coco
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2008
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11. An integrated system for the monitoring of therapy and drug's side effects in Lymphoproliferative disorders.
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Luca Vollero, Ombretta Annibali, Emiliano Schena, Valeria Tomarchio, Giuseppe Cimino, Natalia Cenfra, and Giuseppe Avvisati
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- 2017
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12. Circulating endothelial cell (CEC) kinetic in patients with Multiple Myeloma (MM) who receive Au-HSCT (Autologous Hematopoietic Stem Cell Transplantation)
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Ombretta Annibali, Valeria Tomarchio, Chiara Gregorj, Melania Di Cerbo, Daniele Armiento, Lara Antonelli, Bruno Vincenzi, Carolina Nobile, Michele Vacca, Maria Cristina Tirindelli, and Giuseppe Avvisati
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Pharmacology ,Infectious Diseases ,Oncology ,Drug Discovery ,Pharmacology (medical) ,General Medicine - Abstract
Introduction: Neoangiogenesis has a crucial role in Multiple Myeloma (MM) and Circulating Endothelial Cells (CECs) contribute to neovascularization by inducing tumor progression and metastasis and by repairing damage to bone marrow vasculature after stem cell transplantation (HSC). We recently proved in a national multicenter study, the possibility to reach a high level standardization in CEC count and analysis based on a polychromatic flow cytometry Lyotube (BD). Our study aimed at assessing the kinetics of CECs in patients with MM undergoing autologous hematopoietic stem cell transplantation (Au-HSCT). Methods: Blood samples for analysis were collected at different time points before (T0, T1) and after (T2, T3, T4) Au-HSCT. For each sample, 20 × 106 leukocytes were processed as already described (Lanuti 2016 e 2018) through a multistep procedure. CECs were eventually identified as 7-ADDneg/Syto16pos/CD45neg/CD34pos/CD146pos. Results:Twenty-six MM patients were enrolled in the study. Overall, we observed a constant increase of CECs values from T0 to T3 (day of neutrophil engraftment) followed by decrease at T4 (100 days after transplantation). Using the median value of CECs at T3 we could define a cut-off concentration of 618/mL, with patients with more infective complications having CECs above that value (9/13 vs 2/13; P = .005). Conclusion: CECs value may be a function of endothelial damage caused by conditioning regimen, as suggested by the increase of their level during the engraftment period. A more severe endothelial damage is reflected by the increase of infective complications in patients with higher CECs value at T3.
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- 2023
13. 957 EMERGING FROM THE DARKNESS. SUDDEN CARDIAC DEATH IN CARDIAC AMYLOIDOSIS
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Giorgio Antonelli, Valeria Cammalleri, Valeria Maria De Luca, Ombretta Annibali, Annunziata Nusca, Simona Mega, Myriam Carpenito, Danilo Ricciardi, Fiorella Guerrieri, Giuseppe Avvisati, Gian Paolo Ussia, and Francesco Grigioni
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Cardiology and Cardiovascular Medicine - Abstract
Cardiac amyloidosis (CA) manifests as infiltrative cardiomyopathy with a hypertrophic pattern, usually presenting with heart failure with preserved ejection fraction (HFpEF). In addition, degenerative valvular heart disease, particularly severe aortic stenosis, is commonly seen in patients with CA. However, amyloid fibril deposition may also infiltrate the conduction system and promote the development of electrical disorders, including ventricular tachyarrhythmias (VT), atrio-ventricular block, or acute electromechanical dissociation (EMD). These manifestations can increase the risk of sudden cardiac death (SCD). This review summarizes the pathophysiological mechanisms and risk factors for sudden cardiac death in cardiac amyloidosis and focuses on the major current concerns regarding medical and device management in this challenging scenario. Heart involvement is the major determinant of survival in patient with amyloidosis and a “sudden death” occurs in approximately two-thirds of patients with cardiac amyloidosis. Moreover, the AL amyloid fibrils are shown to be highly cytotoxic to the ventricular myocardial, explaining why ventricular arrhythmias appear more frequently in AL over ATTR. Proposed mechanisms driving electrophysiological manifestations of CA involve intramural coronaries, microvascular ischemia, or patchy myocardium infiltration of amyloid fibrils, causing the development of anatomical re-entrant circuits responsible for ventricular arrhythmia. The prevalence of non-sustained ventricular tachycardia (NSVT) in AL amyloidosis ranges from 5 to 27% with routine monitoring and 100% during the stem cell transplant period. The guidelines don't provide specific indications regarding insertion of implantabile cardioverter defibrillator (ICD) and they don't clarify whether some patients subtypes can benefit from them. Amyloid infiltration into the conduction system enhances the genesis of rhythm disturbances, including fatal ventricular arrhythmias and SCD. Current pharmacological anti-arrhythmic therapies are poorly tolerated in CA, and there are no robust recommendations on the management of ventricular arrhythmias in this subset of patients. Furthermore, the benefit of ICD implantation is highly variable according to the different clinical stages of the disease. Therefore, further studies are needed to create a standardized diagnostic algorithm and appropriate treatment strategy for this special population.
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- 2022
14. Acute promyelocytic leukemia (APL) in very old patients: real-life behind protocols
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Giulio Trapè, Salvatore Perrone, Roberto Latagliata, Emilia Scalzulli, Carmelo Gurnari, Maria Teresa Voso, Malgorzata Monika Trawinska, Maurizio Martelli, Giuseppe Avvisati, Serena Rosati, Enrico Montefusco, Gioia Colafigli, Vincenza Martini, Clara Minotti, Giuseppe Cimino, Agostino Tafuri, Ida Carmosino, Ombretta Annibali, and Massimo Breccia
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Acute promyelocytic leukemia ,medicine.medical_specialty ,Tretinoin ,elderly patients ,Group A ,Group B ,Leukemia, Promyelocytic, Acute ,real-life data ,Acute promyelocytic leukemia apl ,Internal medicine ,Induction therapy ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Retrospective Studies ,Old patients ,business.industry ,Remission Induction ,Retrospective cohort study ,Hematology ,General Medicine ,Settore MED/15 ,medicine.disease ,all-trans retinoic acid ,arsenic trioxide ,Treatment Outcome ,Oncology ,Cohort ,business - Abstract
BACKGROUND Acute promyelocytic leukemia (APL) is uncommon among subjects aged ≥ 70 years and the better therapeutic strategy represents an unmet clinical need. MATERIALS AND METHODS This prompted us to explore our real-life data on a retrospective cohort of 45 older APL patients (≥ 70 years) consecutively diagnosed at eight different hematologic institutions in Latium, Italy, from July 1991 to May 2019. RESULTS Two patients (4.4%) died from early hemorrhagic complications before treatment could begin. Twenty-two patients (51.1%) (Group A) were enrolled or treated according to standard clinical protocols, while 21 (48.8%) (Group B) received an ATRA-based personalized approach due to poor performance status. Morphologic complete remission (CR) after induction therapy was achieved in 33 patients (76.7%) with 100% of patients in Group A and 52.3% in Group B (p
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- 2021
15. The 47th Annual Meeting of the European Society for Blood and Marrow Transplantation: Quality Management Group – Oral Session (O175-O178)
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Teresa Dentamaro, Ilaria Mangione, William Arcese, M.C. Tirindelli, Benedetta Mariotti, Gaspare Adorno, Michele Cedrone, Francesco Marchesi, Mariagiovanna Cefalo, Silvia Miccichè, Agostino Tafuri, Alessandra Picardi, Andrea Mengarelli, Laura Cudillo, Antonella Ferrari, M. Velocci, P. De Fabritiis, R Cerretti, Giuseppe Avvisati, Maria Troiano, G De Angelis, A Bruno, and Marco Andreani
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Transplantation ,Medical education ,business.industry ,media_common.quotation_subject ,education ,Open format ,Attendance ,Hematology ,Continuous training ,Session (web analytics) ,Pandemic ,Medicine ,Quality (business) ,business ,Accreditation ,media_common - Abstract
Background: JACIE (Joint Accreditation Committee ISCTEurope & EBMT) standards define continuous training as a requirement for nurses working in accredited transplant units. Obtaining continuous education can be difficult, so our center decided to implement their own accredited training course. Since 2008 a specific training course, accredited by regular authorities, free of charges in the workplace and held by staff nurses, has been organized. Through all these years, the structure has been modified according to the needs and opinions of the attending nurses. Currently, it consisted of 10 sessions that take place through the year;each session was held at two or three different times (depending on the availability of the speaker), and so nurses from all shifts could attend. At the beginning of the pandemic caused by SARS-COVID 2, in March 2020, we had to suspend the program and reconsider how we could maintain the educational sessions. Methods: From June to November we reinitiated the course. Now, several options were offered to participate: (a) in person, since in our country meetings were restricted to ten people, with previous registration required, (b) synchronously through the Zoom platform, and (c) deferred, as all sessions were recorded so nurses were able to access through the internal training platform of our center. To justify attendance and get the accreditation, when the session was viewed in a delayed manner through the platform, three questions about the viewed session were required to be answered. The course has been accredited by our national system of accreditation. Results: 91 nurses participated in the course. 63.8% of the attendance was virtual. At the end of the course, a satisfaction survey was carried out among the participants. The average score of the questions was 9,25. The lowest score was 8,57 and, the highest, 9,53. There was also a final question in an open format to make comments and suggestions for future editions. Conclusions: Offering quality and up-to-date training to nurses in hematological transplantation wards is one of the JACIE's standards that sometimes is difficult to achieve due to the difficulty of combining nursing schedules and shifts, and the lack of economic resources. The appearance of the pandemic has been an added challenge in order to be able to maintain continuous training as it was established in our center. It was not easy initially to organize it, but it helped us that our center already had a training platform, the availability of online streaming platforms and our background in offering training courses. The high participation and satisfaction of the attendance nurses encourage us to explore and continue new training formats for highly specialized nurses.
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- 2021
16. The Immature Morphology of the Megakaryocytes Present in the Bone Marrow of Patients with Myelofibrosis Reflects Changes in the Frequency of Functionally Distinctive Subpopulations
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Francesca Arciprete, Maria Zingariello, Maria Mazzarini, Paola Verachi, Fabrizio Martelli, Anna Crescenzi, Elisabetta Cerchiara, Giuseppe Avvisati, Paola Guglielmelli, Manjola Balliu, Alessandro Vannucchi, and Anna Rita Migliaccio
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
17. Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): long-term follow-up analysis of a randomised phase 3, open-label study
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Paola Tacchetti, Lucia Pantani, Francesca Patriarca, Maria Teresa Petrucci, Elena Zamagni, Luca Dozza, Monica Galli, Francesco Di Raimondo, Claudia Crippa, Mario Boccadoro, Simona Barbato, Patrizia Tosi, Franco Narni, Vittorio Montefusco, Nicoletta Testoni, Antonio Spadano, Carolina Terragna, Norbert Pescosta, Giulia Marzocchi, Claudia Cellini, Piero Galieni, Sonia Ronconi, Marco Gobbi, Lucio Catalano, Antonio Lazzaro, Giovanni De Sabbata, Clotilde Cangialosi, Fabrizio Ciambelli, Pellegrino Musto, Francesca Elice, Michele Cavo, Renato Fanin, Roberto Foa', Alessandro Rambaldi, Giuseppe Rossi, Pietro Leoni, Paolo Corradini, Giuseppe Torelli, Giuseppe Fioritoni, Sergio Cortelazzo, Giorgio Lambertenghi Deliliers, Giorgio La Nasa, Alfonso Zaccaria, Paolo De Fabritiis, Nicola Cascavilla, Alberto Bosi, Gianpietro Semenzato, Luigi Gugliotta, Filippo Gherlinzoni, Emanuele Angelucci, Massimo Fabrizio Martelli, Maria Concetta Petti, Giuseppe Leone, Angelo Michele Carella, Fabio Ciceri, Armando Santoro, Felicetto Ferrara, Francesco Nobile, Alfonso Maria D'Arco, Alessandro Levis, Luciano Guardigni, Andrea Gallamini, Pier Paolo Fattori, Sergio Morandi, Dino Amadori, Bruno Rotoli, Salvatore Mirto, Giorgio Paladini, Ruggero Mozzana, Graziella Pinotti, Francesco Rodeghiero, Nicola Cantore, Vincenzo Pavone, Enrico Maria Pogliani, Anna Marina Liberati, Ignazio Majolino, Sergio Amadori, Francesco Lauria, Massimo Aglietta, Giovanni Quarta, Sergio Storti, Fortunato Morabito, Silvana Franca Capalbo, Alessandro Massimo Gianni, Vincenzo Mettivier, Vittorio Rizzoli, Carlo Bernasconi, Giuseppe Visani, Michele Pizzuti, Giacinto La Verde, Giuseppe Avvisati, Maurizio Longinotti, Eugenio Gallo, Franco Dammacco, Domenico Russo, Andrea Bacigalupo, Caterina Musolino, Tacchetti P., Pantani L., Patriarca F., Petrucci M.T., Zamagni E., Dozza L., Galli M., Di Raimondo F., Crippa C., Boccadoro M., Barbato S., Tosi P., Narni F., Montefusco V., Testoni N., Spadano A., Terragna C., Pescosta N., Marzocchi G., Cellini C., Galieni P., Ronconi S., Gobbi M., Catalano L., Lazzaro A., De Sabbata G., Cangialosi C., Ciambelli F., Musto P., Elice F., Cavo M., Fanin R., Foa' R., Rambaldi A., Rossi G., Leoni P., Corradini P., Torelli G., Fioritoni G., Cortelazzo S., Lambertenghi Deliliers G., La Nasa G., Zaccaria A., De Fabritiis P., Cascavilla N., Bosi A., Semenzato G., Gugliotta L., Gherlinzoni F., Angelucci E., Martelli M.F., Petti M.C., Leone G., Carella A.M., Ciceri F., Santoro A., Ferrara F., Nobile F., D'Arco A.M., Levis A., Guardigni L., Gallamini A., Fattori P.P., Morandi S., Amadori D., Rotoli B., Mirto S., Paladini G., Mozzana R., Pinotti G., Rodeghiero F., Cantore N., Pavone V., Pogliani E.M., Liberati A.M., Majolino I., Amadori S., Lauria F., Aglietta M., Quarta G., Storti S., Morabito F., Capalbo S.F., Gianni A.M., Mettivier V., Rizzoli V., Bernasconi C., Visani G., Pizzuti M., La Verde G., Avvisati G., Longinotti M., Gallo E., Dammacco F., Russo D., Bacigalupo A., and Musolino C.
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Phases of clinical research ,Transplantation, Autologous ,Dexamethasone ,Bortezomib ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,GIMEMA-MMY-3006 trial, bortezomib, thalidomide, dexamethasone, VTD, double autologous haematopoietic stem-cell transplantation, multiple myeloma ,Multiple myeloma ,Aged ,Intention-to-treat analysis ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Thalidomide ,Transplantation ,Regimen ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Background: The phase 3 GIMEMA-MMY-3006 trial, which compared bortezomib, thalidomide, and dexamethasone (VTD) combination therapy with thalidomide and dexamethasone (TD) as induction therapy before and consolidation therapy after double autologous haematopoietic stem-cell transplantation (HSCT) for newly diagnosed multiple myeloma, showed the superiority of the triplet regimen over the doublet in terms of increased complete response rate and improved progression-free survival. We report the results from the final analysis of the study. Methods: In this randomised, open-label, phase 3 study, patients aged 18–65 years with previously untreated symptomatic multiple myeloma and a Karnofsky Performance Status of 60% or higher were enrolled at 73 centres in Italy. Patients were randomised (1:1) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily orally for the first 14 days and 200 mg daily thereafter) plus dexamethasone (total 320 mg per cycle; 40 mg on days 1–2, 4–5, 8–9, and 11–12 in the VTD regimen, and 40 mg on days 1–4 and 9–12 in the TD regimen), either alone (TD group) or with bortezomib (1·3 mg/m2 intravenously on days 1, 4, 8, and 11; VTD group). After double autologous HSCT, patients received two 35-day cycles of either the VTD or TD regimen, according to random assignment, as consolidation therapy. The primary outcome was the rate of complete response and near complete response after induction (already reported). In this updated analysis we assessed long-term progression-free survival and overall survival (secondary endpoints of the study) with an extended 10-year median follow-up, and analysed the variables influencing survival. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, NCT01134484. Findings: Between May 10, 2006, and April 30, 2008, 480 patients were enrolled and randomly assigned to receive VTD (241 patients) or TD (239 patients). Six patients withdrew consent before start of treatment. 236 (99 [42%] women) in the VTD group and 238 (102 [43%] women) in the TD group were included in the intention-to-treat analysis. The data cutoff date for this analysis was May 31, 2018. Median follow-up for surviving patients was 124·1 months (IQR 117·2–131·7). The 10-year progression-free survival estimate for patients in the VTD group was 34% (95% CI 28–41) compared with 17% (13–23) for the TD group (hazard ratio [HR] 0·62 [95% CI 0·50–0·77]; p
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- 2020
18. Treatment and prognosis of primary pulmonary lymphoma: A long‐term follow‐up study
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Valerio Zoli, Sofia Kovalchuk, Alberto Bosi, Ombretta Annibali, Giuseppe Avvisati, Luigi Rigacci, Ilaria Romano, Michelina Santopietro, Benedetta Puccini, and Roberta Battistini
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Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Lymphoma ,Primary pulmonary lymphoma ,Asymptomatic ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biopsy ,Epidemiology ,Humans ,Medicine ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Medical record ,Disease Management ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Non-Hodgkin's lymphoma ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Bone marrow ,Neoplasm Grading ,medicine.symptom ,business ,Follow-Up Studies ,030215 immunology ,Rare disease - Abstract
Primary pulmonary lymphoma (PPL) is a rare disease with not well-defined optimal treatment. Outcomes and follow-up are variable in published data. Objectives To define the outcome and optimal treatment strategies in PPL. Methods We reviewed the medical records of 49 patients with PPL treated in three Italian Hematological Institutions between 2002 and 2018. Results Thirty-eight (77.5%) cases were indolent PPL, and 11 (22.5%) cases were aggressive PPL. The majority of patients were asymptomatic at diagnosis, early stages (stages IE-IIE), normal serum LDH, no bone marrow involvement, and low or low-intermediate risks of IPI. Local therapy ± immunotherapy or immuno-chemotherapy was possible in 18/49 (37%) patients. Twenty-eight (57%) patients were treated with immuno-chemotherapy after biopsy. Waiting and watching were reported in 3 (6%) patients. Overall, the CR and ORR were 83.7% and 95.9%. With a median follow-up of 62.5 months (range 0.8-199 months), the estimated 5- and 10-year OS rates were 85% and 72.3% for all patients, 89.2% and 80.3% for indolent PPL, and 70.7% and 47.1% for aggressive PPL. Aggressive PPL tended to have a high risk of progression in the first months (P = .056). No advantages were found for indolent PPL who received immuno-chemotherapy or more conservative approaches. Conclusion Our studies confirm the epidemiological and favorable survival of patients with PPL, suggesting a very conservative approach, particularly in indolent subtypes.
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- 2020
19. Characteristics and outcome of acute myeloid leukemia with uncommon retinoic acid receptor-alpha (RARA) fusion variants
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Ombretta Annibali, Roberto Castelli, Francesco Lo-Coco, Franco Locatelli, Oussama Abla, Carmelo Gurnari, Miguel A. Sanz, Jordi Esteve, Anna Maria Testi, Mario Angelini, Pau Montesinos, M Mirabile, Vladimir Lazarevic, Anthony P. Schwarer, Maria Teresa Voso, Michael Dworzak, Elihu H. Estey, Hong-Hu Zhu, Laura Cicconi, Giuseppe Avvisati, Hiroyuki Takahashi, Jeevan Kumar, and Eduardo Magalhães Rego
- Subjects
Adult ,Male ,Adolescent ,Oncogene Proteins, Fusion ,ACUTE PROMYELOCYTIC LEUKEMIA ,Acute myeloid leukaemia ,Disease-Free Survival ,Text mining ,Leukemia, Promyelocytic, Acute ,AML ,Correspondence ,MANAGEMENT ,Humans ,Medicine ,Child ,RC254-282 ,Aged ,Aged, 80 and over ,IDENTIFICATION ,business.industry ,Retinoic Acid Receptor alpha ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Myeloid leukemia ,Hematology ,Translational research ,Middle Aged ,Settore MED/15 ,GENE ,Survival Rate ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Oncology ,Retinoic acid receptor alpha ,Child, Preschool ,LACKING ,Cancer research ,Female ,business ,RESISTANCE - Published
- 2021
20. Emerging from the Darkness. Sudden Cardiac Death in Cardiac Amyloidosis
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Francesco Grigioni, Gian Paolo Ussia, Giuseppe Avvisati, Fiorella Gurrieri, Danilo Ricciardi, Myriam Carpenito, Simona Mega, Annunziata Nusca, Ombretta Annibali, Giorgio Antonelli, Valeria Maria De Luca, and Valeria Cammalleri
- Subjects
General Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2022
21. A Curious Novel Combination of Nucleophosmin (NPM1) Gene Mutations Leading to Aberrant Cytoplasmic Dislocation of NPM1 in Acute Myeloid Leukemia (AML)
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Giovanni Martino, Roberta Rossi, Maria Paola Martelli, Alessandra Venanzi, Paolo Sportoletti, Enrico Tiacci, Giuseppe Avvisati, Ombretta Annibali, Maria Grazia Mameli, and Brunangelo Falini
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Male ,Myeloid ,Cytoplasm ,NPM1 ,Cells ,Active Transport, Cell Nucleus ,Acute ,Gene mutation ,Biology ,acute myeloid leukemia ,QH426-470 ,medicine.disease_cause ,nuclear export signal (NES) ,Mice ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Gene duplication ,medicine ,Genetics ,Animals ,Humans ,Nuclear export signal ,Cells, Cultured ,Genetics (clinical) ,Aged ,030304 developmental biology ,Nuclear Export Signals ,Cell Nucleus ,0303 health sciences ,Mutation ,Nucleophosmin ,Cultured ,Leukemia ,Myeloid leukemia ,Immunohistochemistry ,Molecular biology ,Active Transport ,3. Good health ,Protein Transport ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,NIH 3T3 Cells ,exportin-1/XPO1 ,nucleophosmin - Abstract
Nucleophosmin (NPM1) mutations occurring in acute myeloid leukemia (AML) (about 50 so far identified) cluster almost exclusively in exon 12 and lead to common changes at the NPM1 mutants C-terminus, i.e., loss of tryptophans 288 and 290 (or 290 alone) and creation of a new nuclear export signal (NES), at the bases of exportin-1(XPO1)-mediated aberrant cytoplasmic NPM1. Immunohistochemistry (IHC) detects cytoplasmic NPM1 and is predictive of the molecular alteration. Besides IHC and molecular sequencing, Western blotting (WB) with anti-NPM1 mutant specific antibodies is another approach to identify NPM1-mutated AML. Here, we show that among 382 AML cases with NPM1 exon 12 mutations, one was not recognized by WB, and describe the discovery of a novel combination of two mutations involving exon 12. This appeared as a conventional mutation A with the known TCTG nucleotides insertion/duplication accompanied by a second event (i.e., an 8-nucleotide deletion occurring 15 nucleotides downstream of the TCTG insertion), resulting in a new C-terminal protein sequence. Strikingly, the sequence included a functional NES ensuring cytoplasmic relocation of the new mutant supporting the role of cytoplasmic NPM1 as critical in AML leukemogenesis.
- Published
- 2021
22. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet
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Giuseppe Avvisati, Farhad Ravandi, Uwe Platzbecker, Alan K. Burnett, Pau Montesinos, Elihu H. Estey, Miguel A. Sanz, Harry J. Iland, Pierre Fenaux, Eduardo Magalhães Rego, Eva Lengfelder, Hagop M. Kantarjian, Hartmut Döhner, Bob Löwenberg, Vikram Mathews, Lionel Adès, Nigel H. Russell, Martin S. Tallman, Tomoki Naoe, Sai Juan Chen, Francesco Lo-Coco, and Hematology
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Acute promyelocytic leukemia ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,MEDLINE ,Tretinoin ,Disease ,Hemorrhagic Disorders ,Biochemistry ,Hemorrhagic disorder ,European LeukemiaNet ,Arsenic Trioxide ,Leukemia, Promyelocytic, Acute ,Pregnancy ,Recurrence ,Humans ,Medicine ,Disease management (health) ,Intensive care medicine ,Special Report ,Neoadjuvant therapy ,APL Differentiation Syndrome ,Aged ,business.industry ,Disease Management ,Cell Biology ,Hematology ,medicine.disease ,Practice Guidelines as Topic ,Female ,business - Abstract
Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion–based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all-trans retinoic acid– and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.
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- 2019
23. A novel scoring system for TIGIT expression in classic Hodgkin lymphoma
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Anna Crescenzi, Alba Grifoni, Mariantonietta Tafuri, Ombretta Annibali, Antonella Bianchi, Valeria Tomarchio, Martina Verri, and Giuseppe Avvisati
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Adult ,Male ,Scoring system ,Adolescent ,T cell ,Science ,Immunology ,Mutually exclusive events ,Article ,Cohort Studies ,Young Adult ,TIGIT ,Tumor Microenvironment ,Medicine ,Humans ,Reed-Sternberg Cells ,Receptor ,Cancer ,Multidisciplinary ,business.industry ,Advanced stage ,Middle Aged ,Hodgkin Disease ,Immune checkpoint ,medicine.anatomical_structure ,Cancer research ,Hodgkin lymphoma ,Female ,business - Abstract
Clinical use of immune-checkpoints inhibitors (anti PD-1/PD-L1) resulted very effective for the treatment of relapsed/refractory classic Hodgkin Lymphoma (CHL). Recently, T cell Ig and ITIM domains (TIGIT) has been recognized as an immune checkpoint receptor able to negatively regulate T cell functions. Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. TIGIT expression in T lymphocytes surrounding Hodgkin Reed-Sternberg (HRS) cells was observed in 19/34 patients (56%), of which 11 (58%) had advanced stages. In 16/19 (84%) cases, TIGIT+ peritumoral T lymphocytes showed also PD-1 expression. All 15 TIGIT− patients had PD-L1 expression in HRS cells (100%) while among 19 TIGIT+ patients, 11 (58%) were PD-L1+ and 8 (42%) were PD-L1−. Using a new scoring system for TIGIT immunoreactivity, all TIGIT+ cases with higher score (4/19) were PD-L1−. Our results confirm co-expression of TIGIT and PD-1 in peritumoral T lymphocytes. Of relevance, we demonstrated a mutually exclusive expression of TIGIT and PD-L1 using new TIGIT scoring system able to identify this immunocheckpoints’ modulation. These results pave the way to new therapeutic strategies for relapsed/refractory CHL.
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- 2021
24. Obituary J. W. ten Cate
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Guus Sturk, Menno V. Huisman, Marjolein Peters, Giuseppe Avvisati, Paolo Prandoni, Harry R. Büller, Giancarlo Agnelli, Sander van Deventer, Eric A. van Royen, Marcel Levi, and Cees Breederveld
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First contact ,Presentation ,media_common.quotation_subject ,Subject (philosophy) ,Art history ,Hematology ,Art ,Obituary ,Relation (history of concept) ,Phd students ,media_common - Abstract
Jan Wouter was born in Amsterdam and studied medicine at the University of Amsterdam, specialized in internal medicine, and defended his PhD thesis in 1971 with the subject 'Platelet functions in relation to haemostasis'. He became head of the department of thrombosis and hemostasis of the former Wilhelmina Gasthuis in Amsterdam, which later on, after the Academic Medical Center was formed, extended into the Centre for Thrombosis- Haemostasis-Atherosclerosis and Inflammation Research. In this fertile scientific environment, Jan Wouter, with his immense sense of humour, gift of speech and flamboyant presentation, attracted numerous talented, rebellious and untameable young PhD students, who were seeking a bright future and were magnetized by his appearance. The first contact was nearly always brisk and direct: 'Do you want work really hard? Are you brilliant? How old are you? You can start tomorrow'. Afterwards, later in a nearby cafe, the salaries were conjured out of the magician's hat. The other day, the student learned that hard working with integrity would be the line to follow. Many PhD theses and dozens of top journal articles appeared, thus creating a wonderful scientific perpetuum mobile, engineered by this unique, jovial person with his impressive moustache.
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- 2021
25. Novel NPM1 exon 5 mutations and gene fusions leading to aberrant cytoplasmic nucleophosmin in AML
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Manja Meggendorfer, Orietta Spinelli, Maria Paola Martelli, Brunangelo Falini, Calogero Vetro, Roberta Rossi, Corinne Quadalti, Alessandra Venanzi, Enrico Tiacci, Ombretta Annibali, Stefano Ascani, Roberta Pacini, Torsten Haferlach, Giovanni Martino, Giorgina Specchia, Giuseppe Avvisati, Claudia Haferlach, Francesco Albano, Emanuela Varasano, Francesca Milano, Ilaria Gionfriddo, Francesco Di Raimondo, Lorenzo Brunetti, Franca Falzetti, Alessandro Rambaldi, Barbara Bigerna, Paolo Sportoletti, Valeria Cardinali, Alessia Tabarrini, Raffaella Ciurnelli, Federica Mezzasoma, and Vincenzo Perriello
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Adult ,Male ,Myeloid ,NPM1 ,Immunology ,Biology ,Acute ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,Exon ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Nuclear export signal ,Gene ,030304 developmental biology ,Gene Rearrangement ,0303 health sciences ,Nucleophosmin ,Mutation ,Leukemia ,RNA ,Myeloid leukemia ,Cell Biology ,Hematology ,Exons ,Middle Aged ,Molecular biology ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Female ,Gene Fusion - Abstract
Nucleophosmin (NPM1) mutations in acute myeloid leukemia (AML) affect exon 12, but also sporadically affect exons 9 and 11, causing changes at the protein C-terminal end (tryptophan loss, nuclear export signal [NES] motif creation) that lead to aberrant cytoplasmic NPM1 (NPM1c+), detectable by immunohistochemistry. Combining immunohistochemistry and molecular analyses in 929 patients with AML, we found non–exon 12 NPM1 mutations in 5 (1.3%) of 387 NPM1c+ cases. Besides mutations in exons 9 (n = 1) and 11 (n = 1), novel exon 5 mutations were discovered (n = 3). Another exon 5 mutation was identified in an additional 141 patients with AML selected for wild-type NPM1 exon 12. Three NPM1 rearrangements (NPM1/RPP30, NPM1/SETBP1, NPM1/CCDC28A) were detected and characterized among 13 979 AML samples screened by cytogenetic/fluorescence in situ hybridization and RNA sequencing. Functional studies demonstrated that in AML cases, new NPM1 proteins harbored an efficient extra NES, either newly created or already present in the fusion partner, ensuring its cytoplasmic accumulation. Our findings support NPM1 cytoplasmic relocation as critical for leukemogenesis and reinforce the role of immunohistochemistry in predicting AML-associated NPM1 genetic lesions. This study highlights the need to develop new assays for molecular diagnosis and monitoring of NPM1-mutated AML.
- Published
- 2021
26. Alkaline phosphatase (alp) levels in multiple myeloma and solid cancers with bone lesions: Is there any difference?
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S. Mohamed, F. Stocchi, Ombretta Annibali, Barbara Anaclerico, Svitlana Gumenyuk, Agostina Siniscalchi, Luca Franceschini, Velia Bongarzoni, Maria Cantonetti, Giuseppe Avvisati, Angela Rago, L. Cudillo, Tommaso Caravita, Federico Vozella, O. Venditti, Marco Russano, María de las Olas Palma García, Giuseppe Cimino, E. Cerchiara, Francesco Pisani, Daniele Santini, L. De Rosa, Marco Mariani, M.T. Petrucci, Francesco Pantano, and S Andriani
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Urinary system ,Lytic lesions ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Osteoclast ,medicine ,Clinical significance ,Stage (cooking) ,Multiple myeloma ,business.industry ,Retrospective cohort study ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,MM ,ALP ,Osteoblastic lesions ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Bone lesion ,030220 oncology & carcinogenesis ,Alkaline phosphatase ,lcsh:RC925-935 ,business ,Research Paper - Abstract
Highlights • Plasma ALP could be used as a discriminating marker in presence of bone lesions in solid tumor or MM. • Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. • Lower or normal values, should suggest further investigations such as urinary and serum electrophoresis., Introduction Bone involvement in Multiple Myeloma results from increased osteoclast formation and activity that occurs in proximity to myeloma cells. The role of Alkaline Phosphatse (ALP) in this process and the diagnostic significance of plasma levels in patients with MM are unclear. Aim To compare plasma ALP levels in patients with MM and solid cancers and metastatic lesions to the bone. Results In this observational retrospective study we enrolled 901 patients were enrolled: 440 patients (49%) with Multiple Myeloma, 461 (51%) with solid cancers. All 901 patients had bone lesions. Among patients with Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. This difference is independent of stage, number and type of bone lesions. Conclusion This study suggests that plasma ALP has a different clinical significance in MM than in other neoplasms and could be used as a discriminating marker in presence of bone lesions. In particular, lower or normal values, should suggest further investigations such as urinary and serum electrophoresis, associated with bone marrow aspirate in case of the presence of a monoclonal component, in order to confirm or exclude a MM diagnosis.
- Published
- 2020
27. Endothelial Dysfunction, Fibrinolytic Activity, and Coagulation Activity in Patients With Atrial Fibrillation According to Type II Diabetes Mellitus Status
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Germano Di Sciascio, Barbara Giannetti, Elisabetta Cerchiara, Giuseppe Avvisati, Giuseppe Patti, Raffaele De Caterina, Alessia Delli Veneri, and Edoardo Bressi
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Male ,Carboxypeptidase B2 ,medicine.medical_treatment ,Comorbidity ,030204 cardiovascular system & hematology ,Gastroenterology ,0302 clinical medicine ,Interquartile range ,Atrial Fibrillation ,Insulin ,Endothelial dysfunction ,Aged, 80 and over ,biology ,Atrial fibrillation ,Metformin ,Dabigatran ,medicine.anatomical_structure ,Italy ,Coagulation ,Cardiology ,Female ,Prothrombin ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Endothelium ,030209 endocrinology & metabolism ,Antithrombins ,03 medical and health sciences ,Von Willebrand factor ,Internal medicine ,Diabetes mellitus ,von Willebrand Factor ,medicine ,Humans ,Hypoglycemic Agents ,Aged ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Anticoagulants ,medicine.disease ,Peptide Fragments ,Cross-Sectional Studies ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,biology.protein ,Endothelium, Vascular ,business ,Factor Xa Inhibitors - Abstract
Recent findings in atrial fibrillation (AF) patients receiving oral anticoagulation showed that diabetes without insulin therapy has a thromboembolic risk comparable to nondiabetic patients, whereas only diabetic patients on insulin have a heightened thromboembolic risk. We explored possible pathophysiological correlates of such finding on 90 AF patients on oral anticoagulation, divided according to diabetes status (n = 30 without diabetes; n = 29 with diabetes on oral antidiabetic drugs; n = 31 with insulin-requiring diabetes). We assessed von Willebrand Factor (VWF) concentration (VWF:Ag) and activity (VWF R:Co) as measures of endothelial dysfunction; and thrombin-activatable fibrinolysis inhibitor (TAFI) and prothrombin fragment 1 + 2 (F1+2) levels as markers of fibrinolytic activity and thrombin generation. Values of VWF:Ag, VWF:RCo, and TAFI were similar in the 3 groups. Patients with diabetes requiring insulin had significantly higher levels of F1+2 (median 23.1 pg/ml [interquartile range 17.6; 33.5]) than those without diabetes (16.3 pg/ml [11.5; 22.5], p = 0.036) and diabetic patients on oral antidiabetic drugs (20.6 pg/ml [13.3; 29], p = 0.046). Thus, in AF patients receiving oral anticoagulation, those with diabetes, regardless of the diabetes type (with or without insulin therapy), and those without diabetes have comparable indices of the explored parameters of endothelial dysfunction and fibrinolytic activity. Despite anticoagulant therapy, thrombin generation is selectively higher in diabetic patients' on insulin than in those without diabetes or with diabetes on oral antidiabetic drugs, with no differences between these latter 2 conditions. Thrombin generation might thus be a predominant contributor to the excess of thromboembolic risk in AF patients on insulin-requiring diabetes.
- Published
- 2020
28. Author response for 'Pulmonary Infections in Patients with Myelodysplastic Syndromes Receiving Frontline Azacytidine Treatment'
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Giuseppe Avvisati, Luca Maurillo, Francesco Buccisano, Maria Lucia De Luca, Marco Mancini, Maria Antonietta Aloe Spiriti, Luana Fianchi, Annalina Piccioni, Marianna Criscuolo, Laura Cesini, Ida Carmosino, Alessia Campagna, Maria Teresa Voso, Corrado Girmenia, Paolo de Fabritiis, Robin Foà, Roberto Latagliata, Daniela De Benedittis, Chiara Sarlo, Agostino Tafuri, Massimo Breccia, and Pasquale Niscola
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medicine.medical_specialty ,business.industry ,Internal medicine ,Myelodysplastic syndromes ,medicine ,In patient ,medicine.disease ,business - Published
- 2019
29. Prognostic factors for thrombosis-free survival and overall survival in polycythemia vera: A retrospective analysis of 623 PTS With long follow-up
- Author
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Francesco Buccisano, Ambra Di Veroli, Barbara Anaclerico, Giuseppe Avvisati, Marco Montanaro, Alessandro Andriani, Cristina Santoro, Raffaele Porrini, Agostino Tafuri, Francesca Spirito, Marianna De Muro, Michele Cedrone, Roberto Latagliata, Antonio Spadea, Sabrina Leonetti Crescenzi, Massimo Breccia, and Giuseppe Cimino
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,Thrombosis free survival ,medicine.medical_specialty ,MEDLINE ,Disease-Free Survival ,03 medical and health sciences ,Polycythemia vera ,Internal medicine ,Overall survival ,Retrospective analysis ,Humans ,Medicine ,Polycythemia Vera ,Survival analysis ,Retrospective Studies ,business.industry ,Follow up studies ,Thrombosis ,Retrospective cohort study ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,030104 developmental biology ,Female ,business ,Follow-Up Studies - Published
- 2018
30. Primary cardiac MYC/BCL6 double hit non-Hodgkin lymphoma
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Ombretta Annibali, Massimo Chello, Raffaele Barbato, Giuseppe Deda, Antonio Nenna, Pietro Sedati, Antonella Bianchi, and Giuseppe Avvisati
- Subjects
medicine.medical_specialty ,Vincristine ,Cyclophosphamide ,business.industry ,030204 cardiovascular system & hematology ,BCL6 ,medicine.disease ,Article ,Lymphoma ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Methylprednisolone ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Cardiology ,Pericardium ,Rituximab ,Radiology ,Differential diagnosis ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Cardiac and pericardial involvement by malignant lymphoma is a rare condition. The present case report describes a case of primary cardiac MYC/BCL6 double hit non-Hodgkin lymphoma in the pericardium, and highlights the importance of a prompt diagnosis and aggressive pharmacologic treatment of this disease. In a symptomatic patient, a minimally invasive 3 cm sub-xiphoidal incision was performed under deep sedation with spontaneous ventilation to perform a pericardial biopsy. A 5 cm × 3 cm portion of pericardium was removed from above the right ventricle, thus ameliorating the extrinsic compression on the right chambers. The patient received 6 cycles of immuno-chemotherapy (rituximab plus cyclophosphamide, vincristine, and methylprednisolone), with no complications, achieving complete remission with no symptoms. Malignancies must be excluded in every case of acute pericardial disease with imaging techniques, and lymphomas should be always considered in the differential diagnosis of cardiac tumors. Complete surgical removal of the tumor is not necessary to achieve complete remission, and minimally invasive surgical approaches are an effective tool to confirm diagnosis and allow a precise histologic characterization.
- Published
- 2018
31. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non–High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial
- Author
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Erika Borlenghi, Arnold Ganser, Christian Thiede, Hartmut Döhner, Roberto Cairoli, Mohammed Wattad, Norbert Schmitz, Agostino Cortelezzi, Alfonso Maria D'Arco, Massimo Breccia, Franco Mandelli, Richard F. Schlenk, Mariadomenica Divona, Marco Sborgia, Francesco Albano, Laura Cicconi, Enrico Maria Pogliani, Konstanze Döhner, Claudio Fozza, Giuseppe Avvisati, Francesco Lo-Coco, Michael Lübbert, Felicetto Ferrara, Sergio Amadori, Walter Fiedler, Francesco Fabbiano, Bernd Hertenstein, Helmut R. Salih, Lorella Melillo, Uwe Platzbecker, Alessandro Rambaldi, Giorgio La Nasa, Christian Brandts, Nicola Di Renzo, Christoph Röllig, Hartmut Link, Marco Vignetti, Francesca Paoloni, Eros Di Bona, Fabio Efficace, Peter Brossart, Chiara Frairia, Paola Fazi, Gerhard Ehninger, Mathias Hänel, Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, and Lo-Coco, F
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Male ,0301 basic medicine ,Cancer Research ,Phases of clinical research ,Gastroenterology ,Arsenicals ,law.invention ,0302 clinical medicine ,Arsenic Trioxide ,Leukemia, Promyelocytic, Acute ,Randomized controlled trial ,Maintenance therapy ,Risk Factors ,law ,Antineoplastic Combined Chemotherapy Protocols ,Arsenical ,Cumulative incidence ,Prospective Studies ,Oxides ,Middle Aged ,Leukemia ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Human ,medicine.drug ,Adult ,Acute promyelocytic leukemia ,medicine.medical_specialty ,Adolescent ,Tretinoin ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,neoplasms ,Aged ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Risk Factor ,organic chemicals ,Oxide ,Induction chemotherapy ,medicine.disease ,biological factors ,Surgery ,Prospective Studie ,030104 developmental biology ,Commentary ,business ,Settore MED/15 - Malattie del Sangue - Abstract
Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 109/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.
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- 2017
32. PD-1/PD-L1 expression in extra-medullary lesions of multiple myeloma
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Anna Crescenzi, Michele Donati, Alba Grifoni, Antonella Bianchi, Ombretta Annibali, Giuseppe Avvisati, and Anastasia Pagano
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Adult ,0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Medullary cavity ,Programmed Cell Death 1 Receptor ,Gene Expression ,Disease ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Leukemic Infiltration ,PD-L1 ,medicine ,Humans ,Multiple myeloma ,Aged ,biology ,business.industry ,Bone Marrow Examination ,Hematology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Immune checkpoint ,Staining ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Pd l1 expression ,Multiple Myeloma ,business - Abstract
Multiple myeloma patients may develop extraosseous involvement in the course of the disease making prognosis very poor and new drugs clearly needed. The PD-1/PD-L1 axis has emerged as a master immune checkpoint in antitumor responses and recent studies investigated the role of PD-L1 in multiple myeloma cells; no data however are still available about PD-L1 expression in extramedullary localizations. We demonstrate PD-L1 expression in 4/12 cases of extraosseous myeloma suggesting that these lesions represent a specialized microenvironment. We found presence of PD-1+ infiltrating lymphocytes in all observed cases supporting the relevance of PD-1/PD-L1 checkpoint in extramedullary myeloma. We also investigated the correlation in PD1/PD-L1 staining between marrow staining and EMP lesions.
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- 2016
33. The Coagulopathy in Acute Promyelocytic Leukemia: DIC?
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Giuseppe Avvisati, Jan Wouter ten Cate, and Franco Mandelli
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Acute promyelocytic leukemia ,business.industry ,Cancer research ,Coagulopathy ,Medicine ,business ,medicine.disease - Published
- 2019
34. Health-related quality of life, symptom burden, and comorbidity in long-term survivors of acute promyelocytic leukemia
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Monica Crugnola, Tamara Intermesoli, Marco Vignetti, Nicola Cantore, Gianpaolo Nadali, Claudio Romani, Giuseppe Avvisati, Paola Carluccio, Francesco Cottone, Erika Borlenghi, Stefano D'Ardia, Sergio Amadori, Francesco Fabbiano, Francesco Rodeghiero, Mario Luppi, Marco Sborgia, Massimo Breccia, Fabio Efficace, Francesco Lo Coco, and Francesco Nobile
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Adult ,Male ,0301 basic medicine ,Acute promyelocytic leukemia ,medicine.medical_specialty ,Cancer Research ,Time Factors ,Population ,Comorbidity ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Promyelocytic, Acute ,Quality of life ,Interquartile range ,Sickness Impact Profile ,Surveys and Questionnaires ,Internal medicine ,Hematology ,Oncology ,Severity of illness ,Prevalence ,medicine ,Humans ,Patient Reported Outcome Measures ,Survivors ,education ,Survival rate ,Aged ,education.field_of_study ,business.industry ,Case-control study ,Middle Aged ,Prognosis ,medicine.disease ,humanities ,Survival Rate ,030104 developmental biology ,Italy ,Case-Control Studies ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,business ,Follow-Up Studies - Abstract
The objective of this study was to investigate health-related quality of life (HRQOL), symptom burden, and comorbidity profile in long-term acute promyelocytic leukemia (APL) survivors treated with standard chemotherapy. Overall, 307 long-term APL survivors were invited to participate. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and compared with that of age and sex-matched controls from the general population. Symptom burden was assessed with the MD Anderson Symptom Inventory (MDASI) questionnaire and comorbidity profile was also investigated. Median follow-up time since diagnosis was 14.3 years (interquartile range: 11.1-16.9 years). APL survivors had a statistically and clinically meaningful worse score for the role physical scale of the SF-36 (-9.5; 95% CI, -15.7 to -3.2, P = 0.003) than their peers in the general population. Fatigue was reported as moderate to severe by 29% of patients and 84.4% reported at least one comorbidity. Prevalence of comorbidity in APL survivors was higher than that reported by the general population. Also, marked variations were found in the HRQOL profile by number of comorbidities. Even many years after treatment ends, APL survivors treated with standard chemotherapy do not fully recover as they report HRQOL limitations and a substantial burden of symptoms.
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- 2019
35. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial
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Marco Sborgia, Marco Vignetti, Massimo Breccia, Fabio Efficace, Roberto Cairoli, Hartmut Link, Uwe Platzbecker, Norbert Schmitz, Ombretta Annibali, Agostino Cortelezzi, Francesca Paoloni, Eros Di Bona, Nicola Di Renzo, Alfonso Maria D'Arco, Lorella Melillo, Francesco Lo-Coco, Peter Brossart, Felicetto Ferrara, Chiara Frairia, Franco Mandelli, Christoph Röllig, Laura Cicconi, Claudio Fozza, Konstanze Döhner, Walter Fiedler, Bernd Hertenstein, Francesco Fabbiano, Richard F. Schlenk, Mariadomenica Divona, Francesco Albano, Mohammed Wattad, Maria Teresa Voso, Christian Thiede, Christian Brandts, Paola Fazi, Gerhard Ehninger, Mathias Hänel, Sergio Amadori, Alessandro Rambaldi, Giorgio La Nasa, Helmut R. Salih, Hartmut Döhner, Michael Lübbert, Giuseppe Avvisati, Arnold Ganser, Erika Borlenghi, Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, and Lo-Coco, F
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Adult ,Male ,Oncology ,Acute promyelocytic leukemia ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Retinoic acid ,Tretinoin ,Follow-Up Studie ,law.invention ,Young Adult ,chemistry.chemical_compound ,Leukemia, Promyelocytic, Acute ,Randomized controlled trial ,law ,Germany ,Internal medicine ,medicine ,acute leukemia ,Arsenic trioxide ,Aged ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,All trans ,Hematology ,Long term results ,Middle Aged ,APL ,arsenic trioxide ,medicine.disease ,Clinical trial ,Prospective Studie ,Leukemia ,Treatment Outcome ,Italy ,chemistry ,Female ,business ,Settore MED/15 - Malattie del Sangue ,Human - Published
- 2019
36. Pulmonary Infections in Patients with Myelodysplastic Syndromes Receiving Frontline Azacytidine Treatment
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Giuseppe Avvisati, Pasquale Niscola, Luana Fianchi, Agostino Tafuri, Corrado Girmenia, Roberto Latagliata, Annalina Piccioni, Marianna Criscuolo, Luca Maurillo, Paolo de Fabritiis, Marco Mancini, Maria Teresa Voso, Daniela De Benedittis, Ida Carmosino, Francesco Buccisano, Maria Lucia De Luca, Robin Foà, Chiara Sarlo, Alessia Campagna, Laura Cesini, Massimo Breccia, and Maria Antonietta Aloe Spiriti
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survival rate ,Cancer Research ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,azacitidine ,antineoplastic ,Pulmonary disease ,respiratory tract infections ,Myelodysplastic Syndromes ,azacytidine ,prognosis ,pulmonary infections ,myelodysplastic syndromes ,aged ,antimetabolites ,female ,follow-up studies ,humans ,Lung ,male ,middle aged ,retrospective studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Infection control ,In patient ,Major complication ,Survival analysis ,Acute leukemia ,business.industry ,Myelodysplastic syndromes ,Hematology ,General Medicine ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Bacteremia ,business ,Settore MED/15 - Malattie del Sangue ,030215 immunology - Abstract
Pulmonary infections (PIs) are a major complication of patients with myelodysplastic syndromes (MDS). We retrospectively evaluated 234 MDS patients treated with azacytidine (AZA). The total number of AZA cycles was 2886 (median 8 cycles per patient). There were 111 episodes of PI (3.8% of AZA cycles) in 81 patients (34.6%). PIs were considered of fungal origin in 27 cases (24.3%), associated to bacteremia in 11 cases (9.9%), to influenza infection in two cases (1.8%) and of unknown origin in the remaining 71 cases (64.0%). Forty-five PI episodes were documented in cycles 1 to 4 of AZA (5.1% of 875 cycles) and the remaining 66 episodes beyond the fourth cycle (3.2% of 2011 cycles) (P = .017). Overall, a fungal PI was documented in 13/875 (1.5%) cycles 1 to 4 and in 13/2011 (0.6%) cycles beyond the fourth cycle (P = .001). A baseline chronic pulmonary disease was significantly associated to a higher risk of severe PIs. In the survival analysis, cases of PI in patients who progressed to acute leukemia (PAL) were excluded, in view of the predominant influence of PAL on the outcome of the patients. A PI unrelated to PAL documented during the first 4 AZA cycles was an independent factor predicting lower survival (OR, 2.13; 95% CI, 1.37-3.33; P = .001). In conclusion, PIs are common in MDS patients receiving AZA, in particular during the first cycles of treatment and are associated with an unfavorable outcome. The results of our study raise the issue of the need of a tailored infection prevention strategy.
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- 2019
37. Acute Promyelocytic Leukemia (APL) in Very Elderly Patients: Real-Life behind Protocols
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Ombretta Annibali, Massimo Breccia, Maria Teresa Voso, Carmelo Gurnari, Giulio Trapè, Giuseppe Cimino, Malgorzata Monika Trawinska, Serena Rosati, Enrico Montefusco, Agostino Tafuri, Ida Carmosino, Salvatore Perrone, Emilia Scalzulli, Vincenza Martini, Robin Foà, Clara Minotti, Giuseppe Avvisati, and Roberto Latagliata
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medicine.medical_specialty ,business.industry ,education ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Clinical trial ,Consolidation therapy ,Regimen ,Family medicine ,Cohort ,Honorarium ,Medicine ,Frail elderly ,Lost to follow-up ,business ,health care economics and organizations - Abstract
Introduction APL in the elderly is rare and about 5% of patients with APL are older than 70 years at diagnosis; compared to young adults, prognosis of older patients with APL remains poorer, due to the presence of severe comorbidities and the higher rate of mortality related to induction or consolidation therapy. Aim To evaluate in an unselected real-life cohort of APL patients aged ≥ 70 years the true efficacy of targeted treatments and follow-up of disease. Methods A retrospective cohort of 45 consecutive APL patients (M/F 27/18), aged ≥ 70 years and diagnosed at 8 different hematologic institutions in Lazio, Italy, from July 1991 to May 2019 was analyzed. To avoid possible selection bias, particular attention was given to consider also patients managed outside of clinical trials because of comorbidities at diagnosis and patients dead immediately after APL diagnosis before starting any treatment. Results The median age at diagnosis was 76.6 years (range 70 - 87.1). The main clinical features at diagnosis are shown in Table 1. As to major comorbidities, 28 patients(62.2%) had concomitant cardiologic diseases, 13 (28.8%) had a clinical history of cancer and 11 (24.4%) were affected by diabetes. Forty-three patients (95.5%) started therapy after diagnosis, 2 (4.4%) died before starting treatment from early hemorrhagic complications. Twenty-two patients (51.1%) (Group A) were enrolled in clinical controlled trials or were treated according to clinical controlled trials [13 pts (59.0%) according to AIDA-like regimen, 9 (40.9%) according to APL0406 study], while 21 patients (48,8%) (Group B) received an ATRA-based personalized approach. Overall, complete morphologic remission (CR) after induction therapy was achieved in 33 patients (76.7%); all patients in the Group A achieved CR compared to 11 patients (52.3%) in the Group B (p Conclusions: The present analysis of an unselected cohort of APL patients aged ≥ 70 years highlights that almost half of the patients were not considered eligible for a standard approach as in youngers, and received sub-optimal induction treatments, with a very high rate of early death and dismal rates of CR and OS compared to patients treated with standard therapy. As a consequence, it is mandatory, whenever possible, to adopt standard therapies instead of modified/reduced personalized approaches also in frail elderly patients with APL, to improve their outcome. Disclosures Breccia: BMS: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Celgene: Honoraria. Trawinska:Novartis: Consultancy, Honoraria. Foà:Celltrion: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Latagliata:Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Pfizer: Honoraria.
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- 2019
38. May Tigit (T cell Ig and ITIM domain) Expression be a New Target for Hodgkin Lymphoma?
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Giuseppe Avvisati, Ombretta Annibali, Mariantonietta Tafuri, Anna Crescenzi, Alba Grifoni, Valeria Tomarchio, Antonella Bianchi, and Martina Verri
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biology ,Chlorambucil ,medicine.drug_class ,business.industry ,T cell ,Immunology ,Cell Biology ,Hematology ,Monoclonal antibody ,Biochemistry ,Immune checkpoint ,medicine.anatomical_structure ,TIGIT ,B symptoms ,medicine ,biology.protein ,Cancer research ,Antibody ,medicine.symptom ,business ,Receptor ,medicine.drug - Abstract
Introduction: The use of immune-checkpoints (anti PD-1/PD-L1) resulted very effective in the treatment of relapsed/refractory classical Hodgkin Lymphoma (cHL). T cell Ig and ITIM domains (TIGIT) is another immune checkpoint receptor known to negatively regulate T cell functions. Methods: In this study, we investigated the expression of TIGIT in cHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with cHL referred to Campus Bio-Medico University Hospital for diagnosis and treatment during the last eight years. Results: TIGIT positivity was observed in 19/34 patients (56%), of these 11 (58%) had advanced stages and 10 (52%) B symptoms. Among the 8 patients with IPS ≥ 4, 6 (75%) were TIGIT +. Out of the 19 TIGIT + (score 1 to 3) peritumoral T lymphocytes, 16 (84%) were also PD-1+. While out of 15 TIGIT- peritumoral T lymphocytes only 4 (27%) were PD-1+ and 11 (73%) were PD1- (P=0.001). Moreover all 15 TIGIT- patients were PD-L1+ (100%) while out of 19 TIGIT + patients, 11 (58%) were PD-L1+ and 8 (42%) PD-L1- (P=0.004). Conclusion: This study indicate that the great majority of TIGIT+ patients are also PD-1+, while those who are TIGIT- are all PD-L1+. These results may offer a new therapeutic possibility in the treatment of Relapsed/Refractory (R/R) cHL by the use of anti-TIGIT monoclonal antibodies. Figure
- Published
- 2019
39. A standardized flow cytometry network study for the assessment of circulating endothelial cell physiological ranges
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Gianluca Rotta, Paola Lanuti, Elena Di Gennaro, Natalia Malara, Alfredo Budillon, Mirella Marini, Pasquale Mastroroberto, Valentina Trunzo, Francesca Losa, Silvia Pinna, Maria Cristina Tirindelli, Marco Marchisio, Paolo Doretto, Alessandra Falda, Emma Muggianu, Lorenza Scotti, Camillo Almici, Giuseppe Musolino, Annamaria Diodato, Carlo Vitagliano, Laura Pierdomenico, Fulvio Zullo, Rosa Azzaro, Sebastiano Miscia, María Roca, Melania Di Cerbo, Domenico Russo, Chiara Gregorj, Michele Morelli, Vincenzo Mollace, Arabella Neva, Giovanna Piovani, Pasquale Simeone, Giuseppe Avvisati, Eva Ercolino, Alessandra Leone, Roberta Venturella, Maria Luisa Di Martino, Giuseppina Bologna, Lanuti, P, Simeone, P, Rotta, G, Almici, C, Avvisati, G, Azzaro, R, Bologna, G, Budillon, A, Di Cerbo, M, Di Gennaro, E, Di Martino, M, Diodato, A, Doretto, P, Ercolino, E, Falda, A, Gregorj, C, Leone, A, Losa, F, Malara, N, Marini, M, Mastroroberto, P, Mollace, V, Morelli, M, Muggianu, E, Musolino, G, Neva, A, Pierdomenico, L, Pinna, S, Piovani, G, Roca, M, Russo, D, Scotti, L, Tirindelli, M, Trunzo, V, Venturella, R, Vitagliano, C, Zullo, F, Marchisio, M, Miscia, S, Lanuti, Paola, Simeone, Pasquale, Rotta, Gianluca, Almici, Camillo, Avvisati, Giuseppe, Azzaro, Rosa, Bologna, Giuseppina, Budillon, Alfredo, Di Cerbo, Melania, Di Gennaro, Elena, Di Martino, Maria Luisa, Diodato, Annamaria, Doretto, Paolo, Ercolino, Eva, Falda, Alessandra, Gregorj, Chiara, Leone, Alessandra, Losa, Francesca, Malara, Natalia, Marini, Mirella, Mastroroberto, Pasquale, Mollace, Vincenzo, Morelli, Michele, Muggianu, Emma, Musolino, Giuseppe, Neva, Arabella, Pierdomenico, Laura, Pinna, Silvia, Piovani, Giovanna, Roca, Maria Serena, Russo, Domenico, Scotti, Lorenza, Tirindelli, Maria Cristina, Trunzo, Valentina, Venturella, Roberta, Vitagliano, Carlo, Zullo, Fulvio, Marchisio, Marco, and Miscia, Sebastiano
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Adult ,Male ,0301 basic medicine ,Median Fluorescence Intensity ,Circulating endothelial cell ,Science ,Large population ,Cell Separation ,Biology ,Sensitivity and Specificity ,Article ,Flow cytometry ,Andrology ,Young Adult ,03 medical and health sciences ,Reference Values ,medicine ,Humans ,High potential ,Multidisciplinary ,medicine.diagnostic_test ,Healthy population ,Endothelial Cells ,Hematology ,Middle Aged ,Flow Cytometry ,Healthy Volunteers ,Peripheral blood ,Blood Cell Count ,030104 developmental biology ,Biological Variation, Population ,cardiovascular system ,Feasibility Studies ,Medicine ,Female ,Endothelium, Vascular ,Laboratories ,Biological variability - Abstract
Circulating endothelial cells (CEC) represent a restricted peripheral blood (PB) cell subpopulation with high potential diagnostic value in many endothelium-involving diseases. However, whereas the interest in CEC studies has grown, the standardization level of their detection has not. Here, we undertook the task to align CEC phenotypes and counts, by standardizing a novel flow cytometry approach, within a network of six laboratories. CEC were identified as alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in 269 healthy PB samples. Standardization was demonstrated by the achievement of low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of Median Fluorescence Intensity values of the most stable antigens that allowed CEC identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale = 11.55 CEC/mL). CEC count biological variability and method specificity were finally assessed. Results, obtained on a large population of donors, demonstrate that the established procedure might be adopted as standardized method for CEC analysis in clinical and in research settings, providing a CEC physiological baseline range, useful as starting point for their clinical monitoring in endothelial dysfunctions.
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- 2018
40. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study
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Mohamad Mohty, Evangelos Terpos, Maria-Victoria Mateos, Michele Cavo, Sandra Lejniece, Meral Beksac, Mohamed Amine Bekadja, Wojciech Legiec, Meletios Dimopoulos, Svetlana Stankovic, Maria Soledad Durán, Valerio De Stefano, Alessandro Corso, Yulia Kochkareva, Edward Laane, Christian Berthou, Hans Salwender, Zvenyslava Masliak, Valdas Pečeliūnas, Wolfgang Willenbacher, João Silva, Vernon Louw, Damir Nemet, Zita Borbényi, Uri Abadi, Robert Schou Pedersen, Peter Černelč, Anna Potamianou, Catherine Couturier, Caroline Feys, Florence Thoret-Bauchet, Mario Boccadoro, Mohamed Bekadja, Rose-Marie Hamladji, Hocine Ait Ali, Selma Hamdi, Hadj Touhami, Nourredine Sidi Mansour, Werner Linkesch, Robert Shou Pedersen, Niels Abildgaard, Marju Hein, Jean Richard Eveillard, Abderrazak el Yamani, Philippe Moreau, Laurence Sanhes, Gérard Lepeu, Kamel Laribi, Eric Jourdan, Olivier Fitoussi, Olivier Allangba, Joël Fleury, Martine Escoffre, Riad Benramdane, Guillaume Cartron, Gérard Dine, Eric Legouffe, Hanns-Detlev Harich, Thomas Illmer, Steffen Dörfel, Carla Verena Hannig, Michael Koenigsmann, Gabriele Prange-Krex, Ingo Tamm, Wolfgang Zeller, Michael Maasberg, Rudolf Schlag, Martine Klausmann, Jens Uhlig, Burkhard Alkemper, Stefan Schütz, Hans-Werner Tessen, Benno Mohr, Peter Schmidt, Bernhard Heinrich, Holger Hebart, Gernot Seipelt, Thomas Zoeller, Frank Heits, Clemens Müller-Naendrup, Richard Hansen, Roland Repp, Ludwig Fischer Von Weikersthal, Rudolf Schmits, Jörg Heßling, B. Krammer-Steiner, Viktor Janzen, Michael Schauer, Marcus W. Grüner, Jens Kisro, Claudio Denzlinger, Werner Freier, Christian Junghanss, Martin Görner, Katharina Laichinger, Helmut Ostermann, Heinz Dürk, Georg Hess, Gernot Reich, Panagiota Matsouka, Anastasia Pouli, Achilles Anagnostopoulos, Tamas Masszi, Janos Ivanyi, Arpad Szomor, Arnon Nagler, Hila Magen, Irit Avivi, Miriam Quitt, Antonio Palumbo, Tommaso Za, Daniele Vallisa, Roberto Foa, Alberto Bosi, Angelo Vacca, Francesco Lanza, Giulia Palazzo, Giuseppe Avvisati, Felicetto Ferrara, Ugo Consoli, Maria Cantonetti, Emanuele Angelucci, Catello Califano, Francesco Di Raimondo, Attilio Guarini, Maurizio Musso, Michele Pizzuti, Nicola Giuliani, Antonio Ardizzoia, Nicola Di Renzo, Gianluca Gaidano, Alessandro Gozzetti, Vincenzo Pitini, Gabriella Farina, Riccardo Centurioni, Paolo De Fabritiis, Francesco Iuliano, Giorgio La Nasa, Giacinto La Verde, Fabrizio Pane, Umberto Recine, Maria La Targia, Giuseppe Mineo, Clotilde Cangialosi, Daniele Fagnani, Augusto Federici, Atelda Romano, Giorgina Specchia, Sergio Storti, Velia Bongarzoni, Andrea Bacigalupo, Marco Gobbi, Giancarlo Latte, Donato Mannina, Silvana Capalbo, Mindaugas Jurgutis, Dariusz Woszczyk, Jadwiga Hołojda, Slawomir Gornik, Andrzej Pluta, Elzbieta Morawiec-Szymonik, Slawomira Kyrcz-Krzemien, Wojciech Homenda, Sebastian Grosicki, Kazimierz Sulek, Andrzej Lange, Janusz Kloczko, Jolanta Starzak-Gwozdz, Andrzej Hellmann, Mieczyslaw Komarnicki, Kazimierz Kuliczkowski, Carolina Viveiros, Cristina Gonçalves, Natalia Esefyeva, Julia Kochkareva, Kamil Kaplanov, Elena Volodicheva, Elena Laricheva, Valentina Dergacheva, Marina Chukavina, Natalia Volchenko, Irina Nazarova, Ludmila Anchukova, Elena Ovanesova, Taras Gritsenko, Galina Salogub, Ludmila Magomedova, Irina Kuznetsova, Svetlana Osyunikhina, Olga Serdyuk, Elena Karyagina, Valentina Ivanova, Slovenia Peter Černelč, Corlia Coetzee, Karen Gunther, Dhayanithi Moodley, Soledad Duran, Asunción Echeveste Gutiérrez, Jaime Perez De Oteyza, Francisco Javier Capote, Maria Casanova, Jesus Martin Sanchez, Eduardo Rios-Herranz, Jeronima Ibañez-Garcia, Maria Jose Herranz, Belen Hernandez, Sara Sanchez Sanchez, Fernando Escalante, Fernando Carnicero, Joan Bargay Lleonart, Mercedes Gironella, Rafael Martínez, Ana Lopez De La Guia, Luis Palomera, Rebeca Iglesias, Fernando Solano Ramos, Javier De La Serna, Pedro Garcia Sanchez, Juan Besalduch Vidal, Miguel Diaz Morfa, Turkey – Meral Beksac, Filiz Vural, Yildiz Aydin, Ali Unal, Hakan Goker, Oktay Bilgir, Birol Guvenc, Mehmet Turgut, Gulsum Gulistan Ozet, Ridvan Ali, Maryna Kyselyova, Nataliia Glushko, Renata Vybyrana, Igor Skrypnyk, Natalya Tretyak, Tetiana Kharchevska, Iryna Dyagil, Tetiana Popovs'ka, Vadim Shimanskiy, Tamila Lysa, Hanna Oliynyk, Kateryna Vilchevskaya, Iryna Kryachok, Yuriy Popovych, Natalia Romanyuk, Natalia Yushchenko, Polina Kaplan, Grygoriy Rekhtman, Halyna Pylypenko, Viktor Kozlov, Johannes Drach, Jean-Luc Harousseau, Hermann Einsele, Hartmut Goldschmidt, Thierry Facon, Mauricette Michalet, Valery G. Savchenko, Javier De la Rubia, Gordon Cook, Ulf-Henrik Mellqvist, Heinz Ludwig, Millennium Pharmaceuticals, Janssen Research and Development, Mohty, Mohamad, Terpos, Evangelo, Mateos, Maria-Victoria, Cavo, Michele, Lejniece, Sandra, Beksac, Meral, Bekadja, Mohamed Amine, Legiec, Wojciech, Dimopoulos, Meletio, Stankovic, Svetlana, Durán, Maria Soledad, De Stefano, Valerio, Corso, Alessandro, Kochkareva, Yulia, Laane, Edward, Berthou, Christian, Salwender, Han, Masliak, Zvenyslava, Pečeliūnas, Valda, Willenbacher, Wolfgang, Silva, João, Louw, Vernon, Nemet, Damir, Borbényi, Zita, Abadi, Uri, Pedersen, Robert Schou, Černelč, Peter, Potamianou, Anna, Couturier, Catherine, Feys, Caroline, Thoret-Bauchet, Florence, Boccadoro, Mario, Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, V., Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, T., Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, S., Bongarzoni, V., Bacigalupo, A., Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Department of Clinical Therapeutics, Univesrity of Athens, Universidad de Salamanca- CSIC, The Institute of Hematology and Oncology L. and A. Seràgnoli, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Riga Stradins University (RSU), Ankara University, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Medical University of Lublin, Department of Clinical Therapeutics [Athens, Greece], National and Kapodistrian University of Athens (NKUA), University Clinic of Hematology, Skopje, Complejo Hospitalario de Jaén, Institute of Hematology, Catholic University, Division of Hematology, Foundation IRCCS Policlinico San Matteo, Università degli Studi di Pavia, State Budget Healthcare Insititution of Moscow, North Estonia Medical Centre, Service d'hématologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Asklepios Klinik Altona, Institute of Blood Pathology and Transfusion Medicine, Lviv, Vilnius University Hospital Santariskiu Clinics, Universitätsklinik Innsbruck Innere Medizin V (Innsbruck Austria & Oncotyrol), Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa (INESC-ID), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST)-Instituto de Engenharia de Sistemas e Computadores (INESC), University Health Network, University of the Free State [South Africa], Clinical Hospital Centre Zagreb, Szegedi Tudományegyetem, Meir Medical Center, Regionshospitalet i Holstebro, Medicinsk Afdeling, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Janssen-Cilag, Neuss, Janssen-Cilag [Issy-les-Moulineaux], Janssen Research & Development, Divisione di Ematologia dell' Università di Torino, and Azienda Ospedaliera S. Giovanni Battista di Torino
- Subjects
Male ,Cancer Research ,Boronic Acid ,[SDV]Life Sciences [q-bio] ,bortezomib ,global ,observational study ,routine practice ,stem cell transplantation ,Salvage therapy ,Practice Patterns ,Dexamethasone ,Bortezomib ,Routine practice ,0302 clinical medicine ,Global ,Observational study ,Stem cell transplantation ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Prospective Studies ,Practice Patterns, Physicians' ,Prospective cohort study ,Lenalidomide ,ComputingMilieux_MISCELLANEOUS ,Multiple myeloma ,Aged, 80 and over ,Hematology ,Middle Aged ,Boronic Acids ,3. Good health ,Thalidomide ,Survival Rate ,Treatment Outcome ,Local ,Oncology ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,Adult ,Aged ,Follow-Up Studies ,Humans ,Neoplasm Recurrence, Local ,Salvage Therapy ,medicine.drug ,Human ,medicine.medical_specialty ,NO ,Follow-Up Studie ,03 medical and health sciences ,Internal medicine ,medicine ,Survival rate ,Physicians' ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Settore MED/15 ,medicine.disease ,Transplantation ,Settore MED/15 - MALATTIE DEL SANGUE ,Prospective Studie ,Neoplasm Recurrence ,business ,030215 immunology - Abstract
© 2018 The Authors., [Background]: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. [Patients and Methods]: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months., [Results]: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide., [Conclusion]: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits., Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc.
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- 2018
41. Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients
- Author
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Maria Cantonetti, Maura Statzu, Emanuela Rizzo, Maria Cristina Tirindelli, Elisabetta Riva, Valeria Tomarchio, Giuseppe Avvisati, Chiara Sarlo, Silvia Angeletti, Erika Circhetta, Carolina Scagnolari, Luca Franceschini, Livia Piccioni, and Ombretta Annibali
- Subjects
Cytomegalovirus Infection ,Genetics and Molecular Biology (all) ,0301 basic medicine ,Human cytomegalovirus ,Male ,Viral Diseases ,Heredity ,Lymphoma ,Cell Transplantation ,lcsh:Medicine ,Cytomegalovirus ,Pathology and Laboratory Medicine ,Biochemistry ,Plasma Cell Disorders ,Hematologic Cancers and Related Disorders ,Autologous stem-cell transplantation ,Biochemistry, Genetics and Molecular Biology (all) ,Agricultural and Biological Sciences (all) ,Genotype ,Medicine and Health Sciences ,Blood and Lymphatic System Procedures ,Medicine ,Adolescent ,Adult ,Aged ,Alleles ,Cytomegalovirus Infections ,Female ,Hematopoietic Stem Cell Transplantation ,Humans ,Interferons ,Interleukins ,Lymphoma, Non-Hodgkin ,Middle Aged ,Multiple Myeloma ,Transplantation, Autologous ,Virus Activation ,Young Adult ,Polymorphism, Single Nucleotide ,lcsh:Science ,Multiple myeloma ,education.field_of_study ,Multidisciplinary ,virus diseases ,Hematology ,Single Nucleotide ,Myelomas ,Genetic Mapping ,Infectious Diseases ,Oncology ,Medical Microbiology ,Viral Pathogens ,Viruses ,Human Cytomegalovirus ,Rituximab ,Pathogens ,Stem cell ,Autologous ,Research Article ,medicine.drug ,Herpesviruses ,Population ,Non-Hodgkin ,Surgical and Invasive Medical Procedures ,Variant Genotypes ,Microbiology ,03 medical and health sciences ,Virology ,Genetics ,Myelomas and Lymphoproliferative Diseases ,Polymorphism ,education ,Microbial Pathogens ,Transplantation ,Biology and life sciences ,business.industry ,lcsh:R ,Organisms ,Cancers and Neoplasms ,Proteins ,medicine.disease ,Settore MED/15 ,Viral Replication ,030104 developmental biology ,Genetic Loci ,Immunology ,lcsh:Q ,DNA viruses ,business ,Stem Cell Transplantation - Abstract
Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.
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- 2018
42. PB2386 BEHAVIOUR OF CIRCULATING ENDOTHELIAL CELLS IN AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA
- Author
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D. Armiento, Chiara Gregorj, M. Di Cerbo, L. Antonelli, Valeria Tomarchio, Bruno Vincenzi, M. Tafuri, O. Annibali, Giuseppe Avvisati, Maria Cristina Tirindelli, A. Scardocci, E. Circhetta, and C. Sarlo
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business.industry ,medicine.medical_treatment ,medicine ,Cancer research ,In patient ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,business ,Multiple myeloma - Published
- 2019
43. Prof. Franco Mandelli Leukaemia Visionary. May 12, 1931– July 15, 2018
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Robert Peter Gale, Francesco Lo-Coco, William Arcese, Sergio Amadori, and Giuseppe Avvisati
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Cancer Research ,Medical research ,History ,Oncology ,Library science ,Hematology ,Obituary ,Settore MED/15 ,Cancer - Published
- 2019
44. Endovesical instillation of platelet rich fibrin for treatment of interstitial cystitis: case report of two patients
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Falavolti Cristina, Maurizio Buscarini, Giuseppe Avvisati, Maria Cristina Tirindelli, Tommasangelo Petitti, and Antonella Nicotera
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Bladder Pain Syndrome ,medicine ,Urology ,General Earth and Planetary Sciences ,Interstitial cystitis ,Cystoscopy ,medicine.disease ,business ,Platelet-rich fibrin ,General Environmental Science - Published
- 2017
45. Endothelial progenitor cells, defined by the simultaneous surface expression of VEGFR2 and CD133, are not detectable in healthy peripheral and cord blood
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Sebastiano Miscia, Pasquale Simeone, Giuseppe Avvisati, Valentina Trunzo, Camillo Almici, Vincenzo Mollace, Arabella Neva, Elena Di Gennaro, Marco Marchisio, Natalia Malara, Alfredo Budillon, Mirella Marini, Renato Tozzoli, Alessandra Leone, Chiara Gregorj, Paolo Doretto, Melania Di Cerbo, Gianluca Rotta, Alessandra Falda, and Paola Lanuti
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0301 basic medicine ,Histology ,medicine.diagnostic_test ,CD34 ,Hematopoietic stem cell ,Cell Biology ,Biology ,Molecular biology ,Pathology and Forensic Medicine ,Flow cytometry ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Antigen ,Cord blood ,Immunology ,cardiovascular system ,medicine ,CD146 ,Bone marrow ,Progenitor cell ,circulatory and respiratory physiology - Abstract
Circulating endothelial cells (CEC) and their progenitors (EPC) are restricted subpopulations of peripheral blood (PB), cord blood (CB), and bone marrow (BM) cells, involved in the endothelial homeostasis maintenance. Both CEC and EPC are thought to represent potential biomarkers in several clinical conditions involving endothelial turnover/remodeling. Although different flow cytometry methods for CEC and EPC characterization have been published so far, none of them have reached consistent conclusions, therefore consensus guidelines with respect to CEC and EPC identification and quantification need to be established. Here, we have carried out an in depth investigation of CEC and EPC phenotypes in healthy PB, CB and BM samples, by optimizing a reliable polychromatic flow cytometry (PFC) panel. Results showed that the brightness of CD34 expression on healthy PB and CB circulating cells represents a key benchmark for the identification of CEC (CD45neg/CD34bright/CD146pos) respect to the hematopoietic stem cell (HSC) compartment (CD45dim/CD34pos/CD146neg). This approach, combined with a dual-platform counting technique, allowed a sharp CEC enumeration in healthy PB (n = 38), and resulting in consistent CEC counts with previously reported data (median = 11.7 cells/ml). In parallel, by using rigorous PFC conditions, CD34pos/CD45dim/CD133pos/VEGFR2pos EPC were not found in any healthy PB or CB sample, since VEGFR2 expression was never detectable on the surface of CD34pos/CD45dim/CD133pos cells. Notably, the putative EPC phenotype was observed in all analyzed BM samples (n = 12), and the expression of CD146 and VEGFR2, on BM cells, was not restricted to the CD34bright compartment, but also appeared on the HSC surface. Altogether, our findings suggest that the previously reported EPC antigen profile, defined by the simultaneous expression of VEGFR2 and CD133 on the surface of CD45dim/CD34pos cells, should be carefully re-evaluated and further studies should be conducted to redefine EPC features in order to translate CEC and EPC characterization into clinical practice.
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- 2015
46. PD-1 /PD-L1 checkpoint in hematological malignancies
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Ombretta Annibali, A. Pagano, Anna Crescenzi, Valeria Tomarchio, Giuseppe Avvisati, Alba Grifoni, and Antonella Bianchi
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Cancer Research ,T cell ,Programmed Cell Death 1 Receptor ,Lymphoproliferative disorders ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell surface receptor ,PD-L1 ,Blocking antibody ,medicine ,Humans ,biology ,Mechanism (biology) ,business.industry ,Lymphoma, Non-Hodgkin ,Antibodies, Monoclonal ,Hematology ,medicine.disease ,Hodgkin Disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Monoclonal ,biology.protein ,Cancer research ,Tumor Escape ,business ,030215 immunology - Abstract
Programmed cell death protein 1 (PD-1), is a cell surface receptor with an important role in down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. PD-1/PDL1 axis represents a checkpoint to control immune responses and it is often used as a mechanism of immune escaping by cancers and infectious diseases. Many data demonstrate its important role in solid tumors and report emerging evidences in lymphoproliferative disorders. In this review, we summarized the available data on the role of PD-1/PD-L1 checkpoint in lymphoproliferative diseases and the therapeutics use of monoclonal blocking antibodies.
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- 2017
47. Management of Treatment-Related Complications in APL
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Ombretta Annibali and Giuseppe Avvisati
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Acute promyelocytic leukemia ,medicine.medical_specialty ,Differentiation syndrome ,Pseudotumor cerebri ,business.industry ,Mucocutaneous zone ,Neurotoxicity ,Disease ,medicine.disease ,Gastroenterology ,QT interval ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Arsenic trioxide ,business ,neoplasms - Abstract
Since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL), new toxicities have emerged which may complicate the course of this disease. In this chapter we describe common and rare complications, other than thrombohemorrhagic, observed in patients with APL treated with ATRA and/or ATO as well as their management. Some of these complications are common to both agents (differentiation syndrome, hyperleukocytosis); others are more specific for ATRA (pseudotumor cerebri, mucocutaneous complications, moderate increase in triglyceride levels) or ATO (prolongation of QTc interval, neurotoxicity, and viral reactivation). The early recognition of these complications may, in some patients, improve the cure rate of APL now approaching 85–90% when treated with both these agents.
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- 2017
48. Incidence of venous thromboembolism and use of anticoagulation in hematological malignancies: Critical review of the literature
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Ombretta Annibali, Sergio Siragusa, Mariasanta Napolitano, Giuseppe Avvisati, Annibali, Ombretta, Napolitano, Mariasanta, Avvisati, Giuseppe, and Siragusa, Sergio
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medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,venous thromboembolism ,Low molecular weight heparin ,Hemorrhage ,030204 cardiovascular system & hematology ,Vte prophylaxis ,03 medical and health sciences ,0302 clinical medicine ,Antithrombotic ,medicine ,Animals ,Humans ,cardiovascular diseases ,Intensive care medicine ,Chemotherapy ,business.industry ,Incidence (epidemiology) ,Incidence ,Cancer ,Anticoagulants ,Hematology ,Venous Thromboembolism ,Heparin, Low-Molecular-Weight ,medicine.disease ,Thrombocytopenia ,Severe thrombocytopenia ,Oncology ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,business ,Venous thromboembolism - Abstract
Venous Thromboembolism (VTE) frequently complicates the course of hematologic malignancies (HM) and its incidence is similar to that observed in high-risk solid tumors. Despite that, pharmacologic prophylaxis and treatment of VTE in patients with HM is challenging, mainly because a severe thrombocytopenia frequently complicates the course of treatments or may be present since diagnosis, thus increasing the risk of bleeding. Therefore, in this setting, safe and effective methods of VTE prophylaxis and treatment have not been well defined and hematologists generally refer to guidelines produced for cancer patients that give indications on anticoagulation in patients with thrombocytopenia. In this review, besides to summarize the incidence and the available data on prophylaxis and treatment of VTE in HM, we give some advices on how to use antithrombotic drugs in patients with HM according to platelets count.
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- 2017
49. An integrated system for the monitoring of therapy and drug's side effects in Lymphoproliferative disorders
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Ombretta Annibali, Giuseppe Avvisati, Natalia Cenfra, Emiliano Schena, Valeria Tomarchio, Giuseppe Cimino, and Luca Vollero
- Subjects
0301 basic medicine ,Class (computer programming) ,Home environment ,business.industry ,media_common.quotation_subject ,Continuous monitoring ,Wearable computer ,Lymphoproliferative disorders ,Context (language use) ,medicine.disease ,Lymphoproliferative Disorders ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Risk analysis (engineering) ,030220 oncology & carcinogenesis ,Humans ,Medicine ,Quality (business) ,Smartphone ,business ,Simulation ,Monitoring, Physiologic ,media_common - Abstract
The wide diffusion of telecommunication systems and the availability of cheap computational devices, such as smart wearable, PDA and smartphones, is multiplying the number of collaborative and remote-monitored applications accessible to a large mass of people. In particular, this scenario makes it possible the implementation of specific systems that improve the control of patients with minimal impact on the quality of their lives. This paper moves in this context and presents a general system for the continuous monitoring at home of therapy and disease symptoms. Indeed, starting from a specific application aiming at monitoring patients with Lymphoproliferative disorders and the side effects related to specific drugs used in treatment of these diseases, in this paper we present a more general framework easy customizable to the requirements of different applications. In particular, the proposed system has been designed to be easily tuned to a larger class of disorders and, in our opinion, it can be applied in almost all the scenarios where patients require a strict monitoring of their conditions in their home environment. The paper presents the model, the architecture and the implementation of the system.
- Published
- 2017
50. Primary bone lymphoma of the talus: a challenging diagnosis
- Author
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Giuseppe Avvisati, Valeria Tomarchio, Carlo Selmi, Mariantonietta Tafuri, Marco Massarotti, Ombretta Annibali, Elena Sabattini, Stefano Pileri, Gianluigi Fabbriciani, and Pietro Sedati
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lymphoma, B-Cell ,Pain ,Bone Neoplasms ,Talus ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,business.industry ,General Medicine ,medicine.disease ,Prognosis ,Clinical Practice ,Primary Bone Lymphoma ,Complex regional pain syndrome ,Oncology ,030220 oncology & carcinogenesis ,Radiology ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030217 neurology & neurosurgery - Abstract
Purpose Diagnostic challenges are common in clinical practice and diagnostic or classification criteria for musculoskeletal conditions cannot overshadow clinical skills. Methods We present the case of a young man who complained of prolonged articular pain and mild swelling of the right ankle in the absence of other remarkable data. Apparently fulfilling the Budapest diagnostic criteria for complex regional pain syndrome, the patient was treated accordingly, but the pain increased over time. Then the patient underwent an additional diagnostic workup including synovial and bone biopsies in 2 separate occasions with the second one demonstrating diffuse lymphoid infiltrate compatible with lymphoma. Results The conclusive diagnosis of primary diffuse large B-cell lymphoma of the talus was made and adequate treatment initiated. Conclusions The diagnostic difficulties as well as the importance of a multidisciplinary approach for complex cases are highlighted in this report.
- Published
- 2017
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