23 results on '"Piera Angelillo"'
Search Results
2. Role of NFAT in Chronic Lymphocytic Leukemia and Other B-Cell Malignancies
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Ilenia Sana, Maria Elena Mantione, Piera Angelillo, and Marta Muzio
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nuclear factor of activated T cells ,B-cell receptor ,chronic lymphocytic leukemia ,lymphoma ,lymphoid malignancies ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In recent years significant progress has been made in the clinical management of chronic lymphocytic leukemia (CLL) as well as other B-cell malignancies; targeting proximal B-cell receptor signaling molecules such as Bruton Tyrosine Kinase (BTK) and Phosphoinositide 3-kinase (PI3Kδ) has emerged as a successful treatment strategy. Unfortunately, a proportion of patients are still not cured with available therapeutic options, thus efforts devoted to studying and identifying new potential druggable targets are warranted. B-cell receptor stimulation triggers a complex cascade of signaling events that eventually drives the activation of downstream transcription factors including Nuclear Factor of Activated T cells (NFAT). In this review, we summarize the literature on the expression and function of NFAT family members in CLL where NFAT is not only overexpressed but also constitutively activated; NFAT controls B-cell anergy and targeting this molecule using specific inhibitors impacts on CLL cell viability. Next, we extend our analysis on other mature B-cell lymphomas where a distinct pattern of expression and activation of NFAT is reported. We discuss the therapeutic potential of strategies aimed at targeting NFAT in B-cell malignancies not overlooking the fact that NFAT may play additional roles regulating the inflammatory microenvironment.
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- 2021
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3. Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse
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Chiara Rusconi, Chan Y. Cheah, Toby A. Eyre, David Tucker, Pavel Klener, Eva Giné, Lara Crucitti, Cristina Muzi, Sara Iadecola, Gabriele Infante, Sophie Bernard, Rebecca L. Auer, Chiara Pagani, Monika Duglosz-Danecka, Heidi Mocikova, Tom van Meerten, Emanuele Cencini, Ana Marin-Niebla, Michael E. Williams, Piera Angelillo, Paolo Nicoli, Annalisa Arcari, Lucia Morello, Donato Mannina, Orsola Vitagliano, Roberto Sartori, Annalisa Chiappella, Roberta Sciarra, Piero M. Stefani, Martin Dreyling, John F. Seymour, Carlo Visco, and Stem Cell Aging Leukemia and Lymphoma (SALL)
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Male ,Adult ,Aged, 80 and over ,Central Nervous System ,Immunology ,Lymphoma, Mantle-Cell ,Cell Biology ,Hematology ,Middle Aged ,Biochemistry ,Pyrimidines ,Treatment Outcome ,Humans ,Pyrazoles ,Female ,Neoplasm Recurrence, Local ,Aged ,Retrospective Studies - Abstract
Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood–brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.
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- 2022
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4. MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study
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Ilaria Francaviglia, Paolo Lopedote, Filippo Gagliardi, Fabio Ciceri, Sara Steffanoni, Rita Daverio, Teresa Calimeri, Elena Anghileri, Maria Rosa Terreni, Marianna Sassone, Roberto Furlan, Piera Angelillo, Vittoria Tarantino, Maurilio Ponzoni, Chiara Iacona, Claudio Tripodo, Cristina Belloni, Alessandro Gulino, Daniela De Lorenzo, Massimo Filippi, Marica Eoli, Elena Guggiari, Maria Giulia Cangi, Vittorio Martinelli, Massimo Locatelli, Annamaria Finardi, Andrés J.M. Ferreri, Andrea Falini, Nicoletta Anzalone, Marco Foppoli, Alessandro Nonis, Pietro Mortini, Claudio Doglioni, Angelo Diffidenti, Ferreri, A. J. M., Calimeri, T., Lopedote, P., Francaviglia, I., Daverio, R., Iacona, C., Belloni, C., Steffanoni, S., Gulino, A., Anghileri, E., Diffidenti, A., Finardi, A., Gagliardi, F., Anzalone, N., Nonis, A., Furlan, R., De Lorenzo, D., Terreni, M. R., Martinelli, V., Sassone, M., Foppoli, M., Angelillo, P., Guggiari, E., Falini, A., Mortini, P., Filippi, M., Tarantino, V., Eoli, M., Ciceri, F., Doglioni, C., Tripodo, C., Locatelli, M., Cangi, M. G., Ponzoni, M., Ferreri A.J.M., Calimeri T., Lopedote P., Francaviglia I., Daverio R., Iacona C., Belloni C., Steffanoni S., Gulino A., Anghileri E., Diffidenti A., Finardi A., Gagliardi F., Anzalone N., Nonis A., Furlan R., De Lorenzo D., Terreni M.R., Martinelli V., Sassone M., Foppoli M., Angelillo P., Guggiari E., Falini A., Mortini P., Filippi M., Tarantino V., Eoli M., Ciceri F., Doglioni C., Tripodo C., Locatelli M., Cangi M.G., and Ponzoni M.
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Lymphoma ,Biopsy ,Concordance ,interleukin-10 ,diffuse large B-cell lymphoma ,Mutation, Missense ,Central Nervous System Neoplasms ,03 medical and health sciences ,primary CNS lymphoma ,0302 clinical medicine ,Cerebrospinal fluid ,hemic and lymphatic diseases ,Biomarkers, Tumor ,TaqMan ,medicine ,Humans ,diffuse large B-cell lymphoma, interleukin-10, interleukin-6, MYD88 L265P mutation, primary CNS lymphoma ,Prospective cohort study ,Aged ,medicine.diagnostic_test ,business.industry ,interleukin-6 ,Primary central nervous system lymphoma ,Hematology ,Middle Aged ,medicine.disease ,Interleukin-10 ,Neoplasm Proteins ,MYD88 L265P mutation ,Amino Acid Substitution ,030220 oncology & carcinogenesis ,Myeloid Differentiation Factor 88 ,Female ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n=36) and relapsed (n=27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.
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- 2021
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5. Safety and efficacy of a dose-dense short-term therapy in patients with MYC-translocated aggressive lymphoma
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Andrés J. M. Ferreri, Piera Angelillo, Federico Erbella, Chiara Cattaneo, Luisa Verga, Arben Lleshi, Bernardino Allione, Maurilio Ponzoni, Fabio Facchetti, Chiara Pagani, Marco Foppoli, Lorenza Pecciarini, Marianna Sassone, Sara Steffanoni, Elena Flospergher, Giuseppe Rossi, Michele Spina, and Alessandro Re
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Lymphoma, B-Cell ,Lymphoma ,Hematopoietic Stem Cell Transplantation ,Cytarabine ,COVID-19 ,HIV Infections ,Hematology ,Transplantation, Autologous ,Burkitt Lymphoma ,Antibodies, Monoclonal, Murine-Derived ,Vincristine ,Doxorubicin ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Prednisone ,Rituximab ,Cyclophosphamide ,In Situ Hybridization, Fluorescence ,Etoposide ,Retrospective Studies - Abstract
Patients with aggressive B-cell lymphoma and MYC rearrangement at fluorescence in situ hybridization exhibit poor outcome after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In the last decade, 68 patients with Burkitt lymphoma ([BL] n = 46) or high-grade B-cell lymphoma ([HGBCL] single, double, or triple hit; n = 22) were treated with a dose-dense, short-term therapy termed “CARMEN regimen” at 5 Italian centers. Forty-six (68%) patients were HIV+. CARMEN included a 36-day induction with sequential, single weekly doses of cyclophosphamide, vincristine, rituximab, methotrexate, etoposide, and doxorubicin plus intrathecal chemotherapy, followed by high-dose-cytarabine–based consolidation. Patients who did not achieve complete remission (CR) after induction received BEAM (carmustina, etoposide, cytarabine, melfalan)-conditioned autologous stem cell transplantation (ASCT) after consolidation. Sixty-one (90%) patients completed induction, and 59 (87%) completed consolidation. Seventeen patients received ASCT. Grade 4 hematological toxicity was common but did not cause treatment discontinuation; grade 4 nonhematological toxicity was recorded in 11 (16%) patients, with grade 4 infections in 6 (9%). Six (9%) patients died of toxicity (sepsis in 4, COVID-19, acute respiratory distress syndrome). CR rate after the whole treatment was 73% (95% confidence interval [CI], 55% to 91%) for patients with HGBCL and 78% (95% CI, 66% to 90%) for patients with BL. At a median follow-up of 65 (interquartile range, 40-109) months, 48 patients remain event free, with a 5-year progression-free survival of 63% (95% CI, 58% to 68%) for HGBCL and 72% (95% CI, 71% to 73%) for BL, with a 5-year overall survival (OS) of 63% (95% CI, 58% to 68%) and 76% (95% CI, 75% to 77%), respectively. HIV seropositivity did not have a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas.
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- 2022
6. Anti-CD20 rechallenge with ofatumumab in relapsed/refractory splenic marginal zone lymphoma: the MORE trial
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Lydia Scarfò, Silvia Ferrari, Anna Maria Frustaci, Monica Tani, Alessia Bari, Eloise Scarano, Maria Colia, Pamela Ranghetti, Piera Angelillo, Paola Ronchi, Maurilio Ponzoni, Andrés J. M. Ferreri, and Paolo Ghia
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Lymphoma ,Humans ,Hematology ,Neoplasm Recurrence, Local ,Antibodies, Monoclonal, Humanized ,Antigens, CD20 ,Leukemia, Lymphocytic, Chronic, B-Cell - Published
- 2022
7. Continuous positive airway pressure and pronation outside the Intensive Care Unit in COVID-19 acute respiratory distress syndrome
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Alberto Zangrillo, Flavia Di Scala, Giuseppe A. Ramirez, Piera Angelillo, Stefano Turi, Sarah Damanti, Antonella Castagna, Clarissa Centurioni, Paolo Silvani, Francesco Carcò, Francesco De Cobelli, Raffaella Scotti, Andrea Assanelli, Caterina Conte, Lorenzo Dagna, Giovanni Landoni, Luca Cabrini, Alessandro Marinosci, Anna Morgillo, Agnese Gobbi, Enrica Bozzolo, Elena Castelli, Moreno Tresoldi, Barbara Calcaterra, Ramirez, Giuseppe A, Bozzolo, Enrica P, Castelli, Elena, Marinosci, Alessandro, Angelillo, Piera, Damanti, Sarah, Scotti, Raffaella, Gobbi, Agnese, Centurioni, Clarissa, Di Scala, Flavia, Morgillo, Anna, Castagna, Antonella, Conte, Caterina, Assanelli, Andrea, De Cobelli, Francesco, Calcaterra, Barbara, Cabrini, Luca, Carcó, Francesco, Turi, Stefano, Silvani, Paolo, Dagna, Lorenzo, Zangrillo, Alberto, Landoni, Giovanni, and Tresoldi, Moreno
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Adult ,ARDS ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,law.invention ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,law ,Medicine ,Humans ,Pronation ,Continuous positive airway pressure ,Respiratory physiotherapy ,Respiratory Distress Syndrome ,Respiratory distress ,Continuous Positive Airway Pressure ,business.industry ,COVID-19 ,General Medicine ,medicine.disease ,Intensive care unit ,Intensive Care Units ,030220 oncology & carcinogenesis ,Emergency medicine ,030211 gastroenterology & hepatology ,business ,Noninvasive ventilation ,Cohort study - Abstract
The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the ntensive care unit during a pandemic. BACKGROUND: The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the Intensive Care Unit during a pandemic.METHODS: In this cohort study performed in February-May 2020 in a large teaching hospital in Milan, COVID-19 patients with adult respiratory distress syndrome receiving continuous positive airway pressure (positive end-expiratory pressure =10 cm H2O, FiO(2)=0.6, daily treatment duration: 4 x3h-cycles) and respiratory physiotherapy including pronation outside the Intensive Care Unit were followed-up.RESULTS: Of 90 acute respiratory distress syndrome (ARDS) patients treated with continuous positive airway pressure (45/90, 50% pronated at least once) outside the Intensive Care Unit and with a median (interquartile) follow-up of 37 (1146) days, 45 (50%) were discharged at home, 28 (31%) were still hospitalized, and 17 (19%) died. Continuous positive airway pressure failure was recorded for 35 (39%) patients. Patient mobilization was associated with reduced failure rates (P=0.033). No safety issues were observed.CONCLUSIONS: Continuous positive airway pressure with patient mobilization (including pronation) was effective and safe in patients with ARDS due to COVID-19 managed outside the Intensive Care Unit setting during the pandemic.
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- 2022
8. SAFETY AND EFFICACY OF THE 'CARMEN' REGIMEN, A NEW DOSE‐DENSE SHORT‐TERM THERAPY IN PATIENTS WITH AGGRESSIVE B‐CELL LYMPHOMA AND MYC REARRANGEMENT
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Alessandro Re, Giulio Rossi, Anna Ferreri, Luisa Verga, M. Ponzoni, Fabio Facchetti, Marco Foppoli, Bernardino Allione, Marianna Sassone, Chiara Cattaneo, Michele Spina, Piera Angelillo, A. Lleshi, Chiara Pagani, F Erbella, C Liberatore, L Pecciarini, and E Flospergher
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Cancer Research ,medicine.medical_specialty ,Vincristine ,Cyclophosphamide ,business.industry ,macromolecular substances ,Hematology ,General Medicine ,Neutropenia ,medicine.disease ,Gastroenterology ,carbohydrates (lipids) ,Tumor lysis syndrome ,stomatognathic diseases ,Regimen ,Oncology ,Tolerability ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Mucositis ,Rituximab ,business ,medicine.drug - Abstract
Introduction: Patients (pts) with aggressive B-cell lymphoma and MYC rearrangement exhibits poor outcome after R-CHOP treatment. In the last decade, these pts were treated with a new dose-dense, short-term therapy termed “CARMEN”, at several Italian Centers. Excellent efficacy and safety profile have been reported in HIV/AIDS pts with high-risk Burkitt lymphoma (BL) [Ferreri et al. BJH 2021], but its efficacy in pts with high-grade B-cell lymphoma with MYC rearrangement (HGBCL) remains to be defined. Herein, we report a retrospective series of consecutive pts with BL or HGBCL treated with CARMEN regimen. Methods: Either HIV-negative and HIV-positive pts aged 18-80 years with BL or HGBCL and MYC rearrangement positive by FISH were treated with CARMEN regimen, which includes a single 36-day induction course of sequential doses of cyclophosphamide, vincristine, rituximab, methotrexate, VP16, and doxorubicin plus intrathecal chemotherapy, followed by consolidation with HD-cytarabine ± cisplatin. Pts who did not achieve complete remission (CR) after induction received BEAM/ASCT after consolidation. Results: 63 pts (22 HGBCL;41 BL) received the CARMEN regimen (Table). Treatment was well tolerated: 56 (89%) pts completed the induction, and 55 (87%) completed the consolidation. G4 hematological toxicity during induction was neutropenia in 48 (76%) pts, thrombocytopenia in 24 (38%) and anemia in 7 (11%), which were recorded after consolidation in 34 (62%), 38 (69%) and 1 (2%) pt, respectively. G4 non hematological toxicity was uncommon: mucositis in 4 (6%) pts and tumor lysis syndrome in 1 (2%) during induction, and heart failure and bleeding in 1 (2%) pt each after consolidation. G4 infections were recorded in 4 (6%) pts during induction and in 2 (3%) after consolidation. Induction and consolidation doses were reduced in 6 (9%) and 4 (7%) pts, respectively. Seven HGBCL and 9 BL pts received ASCT, with expected tolerability. 4 HGBCL and 2 BL pts died of toxicity (sepsis in 4;respiratory failure;COVID-19), with a TRM of 9%. After induction, 18 (82%) HGBCL and 37 (90%) BL pts achieved a response, which was CR in 10 (45%) and 26 (63%) pts, respectively. After the whole treatment, 15 (68%) HGBCL pts and 32 (78%) BL pts achieved a CR, and, at a median follow-up of 54 (2-131) months, 15 (100%) HGBCL and 29 (91%) BL pts remain relapse-free, with a 5-yr PFS of 67% and 70%, respectively. 15 HGBCL and 32 BL pts are alive, with a 5-yr OS of 66% and 77%, respectively. HIV seropositivity did not modify outcome. Age and LDH level were independently associated with OS. Conclusions: With the limitations of a retrospective series, this study shows that CARMEN is a safe and active treatment both in HIVnegative and-positive pts with HGBCL and MYC rearrangement and BL. Survival figures in HGBCL pts compare favorably with results reported with R-CHOP or analogous, and are similar to those achieved in BL pts.
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- 2021
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9. PROGNOSTIC FACTORS, MANAGEMENT AND OUTCOME OF AN INTERNATIONAL SERIES OF 41 PATIENTS WITH PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA (PMLBCL) AND CENTRAL NERVOUS SYSTEM (CNS) INVOLVEMENT
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M. Ponzoni, Piera Angelillo, M. M.B Salvador Chalup, C. Muzi, Maria Dimou, Potito Rosario Scalzulli, F. L. Nogueira, Emilio Iannitto, D. Onofrillo, Anna Ferreri, Marco Foppoli, Monica Tani, F. Cocito, P. Ramakrishnan, Alessia Castellino, T. Calimeri, Vittoria Tarantino, P. L. Zinzani, Kate Cwynarski, Alessandra Tucci, Felicetto Ferrara, T.P. Vassilakopoulos, G. Cabras, Andrew Davies, Luigi Petrucci, Andrea Ferrario, Sotirios G. Papageorgiou, Maria Chiara Tisi, and Luca Arcaini
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Oncology ,Cancer Research ,Series (stratigraphy) ,medicine.medical_specialty ,business.industry ,Central nervous system ,CNS Involvement ,Hematology ,General Medicine ,medicine.anatomical_structure ,Internal medicine ,medicine ,Primary Mediastinal Large B-Cell Lymphoma ,business - Published
- 2021
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10. Diagnostic and Clinical Impact of Staging 18F-FDG PET/CT in Mantle-Cell Lymphoma: A Two-Center Experience
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Raffaele Giubbini, Alessandra Tucci, Domenico Albano, Luigi Gianolli, Andrés José Maria Ferreri, Giovanni Bosio, Paola Ferro, Francesco Bertagna, Piera Angelillo, Alessandro Re, and Federico Fallanca
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Cancer Research ,PET/CT ,030218 nuclear medicine & medical imaging ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Bone marrow ,PET-CT ,Mantle cell lymphoma ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Hematology ,Gastrointestinal disease ,medicine.disease ,Lymphoma ,18F-FDG ,medicine.anatomical_structure ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,Nuclear medicine - Abstract
Introduction The diagnostic accuracy of fluorine-18–fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging mantle-cell lymphoma has not yet investigated. The aim of this 2-center retrospective study was to investigate the utility of 18F-FDG PET/CT in assessing nodal, splenic, bone marrow (BM), and gastrointestinal (GI) disease compared to CT, BM, and GI endoscopy; and to assess its clinical impact. Patients and Methods One hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ. Results All patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2. Conclusion 18F-FDG PET/CT showed excellent detection rate in nodal and splenic disease—a rate better than CT. For BM and GI evaluation, in order to reach good accuracy, the selection of patients and the use of specific criteria for evaluation of these organs seems to be crucial. Moreover, PET/CT altered the management and therapeutic approach in about 20% of patients.
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- 2019
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11. Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy
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Elena Moizo, Stefano Turi, Corrado Campochiaro, Alberto Zangrillo, Cristina Mattioli, Pasquale Nardelli, Paolo Silvani, Martina Crivellari, Giovanni Landoni, Marianna Sartorelli, Maria Grazia Calabrò, Fabio Ciceri, Francesco Giuseppe Nisi, Maria Luisa Azzolini, Giovanni Borghi, Marina Pieri, Antonio Dell'Acqua, Fabrizio Monaco, Martina Baiardo Redaelli, Caterina Conte, Alessandro Belletti, Ary Serpa Neto, Gabriele Valsecchi, Piera Angelillo, Evgeny Fominskiy, Cristina Barberio, Milena Mucci, Luigi Beretta, Rinaldo Bellomo, Anna Mara Scandroglio, Alfredo Ravizza, Stefano Tentori, Lorenzo Dagna, Giacomo Monti, Intensive Care Medicine, Fominskiy, E. V., Scandroglio, A. M., Monti, G., Calabro, M. G., Landoni, G., Dell'Acqua, A., Beretta, L., Moizo, E., Ravizza, A., Monaco, F., Campochiaro, C., Pieri, M., Azzolini, M. L., Borghi, G., Crivellari, M., Conte, C., Mattioli, C., Silvani, P., Mucci, M., Turi, S., Tentori, S., Baiardo Redaelli, M., Sartorelli, M., Angelillo, P., Belletti, A., Nardelli, P., Nisi, F. G., Valsecchi, G., Barberio, C., Ciceri, F., Serpa Neto, A., Dagna, L., Bellomo, R., and Zangrillo, A.
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Male ,medicine.medical_specialty ,Continuous Renal Replacement Therapy ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,030232 urology & nephrology ,Hospital mortality ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Prevalence ,medicine ,Humans ,Hospital Mortality ,Renal replacement therapy ,Stage (cooking) ,Aged ,Ventilators, Mechanical ,Coronavirus disease 2019 ,SARS-CoV-2 ,business.industry ,urogenital system ,Acute kidney injury ,COVID-19 ,Hematology ,General Medicine ,Middle Aged ,Tertiary care hospital ,medicine.disease ,Respiration, Artificial ,Methods observational ,female genital diseases and pregnancy complications ,Coronavirus ,Critical care ,Treatment Outcome ,Nephrology ,Emergency medicine ,Female ,business ,Research Article ,Healthcare system - Abstract
Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. Methods: Observational study in a tertiary care hospital in Milan, Italy. Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.
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- 2021
12. COVID-19 in recipients of allogeneic stem cell transplantation: favorable outcome
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Carlo Messina, Raffaella Greco, Jacopo Peccatori, Sarah Marktel, Sara Mastaglio, Maria Teresa Lupo-Stanghellini, Francesca Farina, Raffaella Milani, Fabio Ciceri, Lorenzo Lazzari, Andrea Assanelli, Elisabetta Xue, Piera Angelillo, Federico Erbella, Maria Pia Cicalese, Stefania Girlanda, Chiara Oltolini, Simona Piemontese, Consuelo Corti, Massimo Locatelli, Lupo-Stanghellini, M. T., Xue, E., Mastaglio, S., Oltolini, C., Angelillo, P., Messina, C., Piemontese, S., Girlanda, S., Farina, F., Lazzari, L., Cicalese, M. P., Erbella, F., Greco, R., Locatelli, M., Milani, R., Peccatori, J., Corti, C., Marktel, S., Assanelli, A., and Ciceri, F.
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Transplantation ,2019-20 coronavirus outbreak ,Bone marrow transplantation ,Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Hematopoietic Stem Cell Transplantation ,COVID-19 ,Hematology ,Virology ,Text mining ,Correspondence ,Infectious diseases ,Medicine ,Humans ,Transplantation, Homologous ,Favorable outcome ,Stem cell ,business - Published
- 2021
13. Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial
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Letterio S. Politi, Daniela De Lorenzo, Andrés J.M. Ferreri, Eltjona Rrapaj, Claudio Bordignon, Vittoria Tarantino, Fabio Ciceri, Angelo Corti, Eloise Scarano, Nicoletta Anzalone, Paolo Lopedote, Gian Marco Conte, Piera Angelillo, Maurilio Ponzoni, Marianna Sassone, Teresa Calimeri, Flavio Curnis, Federico Fallanca, Marco Foppoli, Alessandro Nonis, Giovanni Citterio, Dario Cattaneo, Elena Guggiari, Sara Steffanoni, Ferreri, A. J. M., Calimeri, T., Ponzoni, M., Curnis, F., Conte, G. M., Scarano, E., Rrapaj, E., De Lorenzo, D., Cattaneo, D., Fallanca, F., Nonis, A., Foppoli, M., Lopedote, P., Citterio, G., Politi, L. S., Sassone, M., Angelillo, P., Guggiari, E., Steffanoni, S., Tarantino, V., Ciceri, F., Bordignon, C., Anzalone, N., and Corti, A.
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Oncology ,Vincristine ,medicine.medical_specialty ,Clinical Trials and Observations ,medicine.medical_treatment ,Recombinant Fusion Proteins ,NGR-hTNF ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cyclophosphamide ,Lenalidomide ,Chemotherapy ,business.industry ,Tumor Necrosis Factor-alpha ,Standard treatment ,Primary central nervous system lymphoma ,Endothelial Cells ,Hematology ,medicine.disease ,Chemotherapy regimen ,Doxorubicin ,Prednisone ,Rituximab ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment of diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system (CNS) (primary central nervous system lymphoma [PCNSL]) is an exception because of the low CNS bioavailability of related drugs. NGR–human tumor necrosis factor (NGR-hTNF) targets CD13+ vessels, enhances vascular permeability and CNS access of anticancer drugs, and provides the rationale for the treatment of PCNSL with R-CHOP. Herein, we report activity and safety of R-CHOP preceded by NGR-hTNF in patients with PCNSL relapsed/refractory to high-dose methotrexate-based chemotherapy enrolled in a phase 2 trial. Overall response rate (ORR) was the primary endpoint. A sample size of 28 patients was considered necessary to demonstrate improvement from 30% to 50% ORR. NGR-hTNF/R-CHOP would be declared active if ≥12 responses were recorded. Treatment was well tolerated; there were no cases of unexpected toxicities, dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with confirmed tumor response in 21 patients (75%; 95% confidence interval, 59%-91%), which was complete in 11. Seventeen of the 21 patients with response to treatment received consolidation (ASCT, WBRT, and/or lenalidomide maintenance). At a median follow-up of 21 (range, 14-31) months, 5 patients remained relapse-free and 6 were alive. The activity of NGR-hTNF/R-CHOP is in line with the expression of CD13 in both pericytes and endothelial cells of tumor vessels. High plasma levels of chromogranin A, an NGR-hTNF inhibitor, were associated with proton pump inhibitor use and a lower remission rate, suggesting that these drugs should be avoided during TNF-based therapy. Further research on this innovative approach to CNS lymphomas is warranted. The trial was registered as EudraCT: 2014-001532-11.
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- 2020
14. Author response for 'LONG-LASTING EFFICACY AND SAFETY OF LENALIDOMIDE MAINTENANCE IN PATIENTS WITH RELAPSED DIFFUSE LARGE B-CELL LYMPHOMA WHO ARE NOT ELIGIBLE FOR OR FAILED AUTOLOGOUS TRANSPLANTATION'
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Michele Spina, Renato Zambello, Piera Angelillo, C. Rusconi, Alberto Fabbri, Eloise Scarano, Sara Steffanoni, Caterina Cecchetti, Fabio Ciceri, Marianna Sassone, Stefano Volpetti, T. Calimeri, Maurizio Frezzato, Maurilio Ponzoni, Alice Di Rocco, Vittoria Tarantino, Annalisa Arcari, A. J. M. Ferreri, Giovanni Bertoldero, Salvatore Perrone, Daniela De Lorenzo, Francesco Zaja, Alessandro Re, Marco Foppoli, Caterina Stelitano, and Alessandro Nonis
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Long lasting ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Autologous transplantation ,In patient ,medicine.disease ,business ,Diffuse large B-cell lymphoma ,Lenalidomide ,medicine.drug - Published
- 2020
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15. Long-lasting efficacy and safety of lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for or failed autologous transplantation
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Eloise Scarano, Vittoria Tarantino, Sara Steffanoni, Piera Angelillo, Chiara Rusconi, C. Cecchetti, Maurilio Ponzoni, Marco Foppoli, Alessandro Re, Caterina Stelitano, Alessandro Nonis, Salvatore Perrone, Michele Spina, Stefano Volpetti, Maurizio Frezzato, Marianna Sassone, Renato Zambello, Alice Di Rocco, Annalisa Arcari, Fabio Ciceri, Andrés J.M. Ferreri, Alberto Fabbri, Daniela De Lorenzo, Francesco Zaja, Teresa Calimeri, Giovanni Bertoldero, Ferreri, Ajm, Sassone, M, Angelillo, P, Zaja, F, Re, A, Di Rocco, A, Spina, M, Fabbri, A, Stelitano, C, Frezzato, M, Volpetti, S, Zambello, R, Rusconi, C, De Lorenzo, D, Scarano, E, Arcari, A, Bertoldero, G, Nonis, A, Calimeri, T, Perrone, S, Cecchetti, C, Tarantino, V, Steffanoni, S, Foppoli, M, Ciceri, F, Ponzoni, M., Ferreri, A. J. M., Sassone, M., Angelillo, P., Zaja, F., Re, A., Di Rocco, A., Spina, M., Fabbri, A., Stelitano, C., Frezzato, M., Volpetti, S., Zambello, R., Rusconi, C., De Lorenzo, D., Scarano, E., Arcari, A., Bertoldero, G., Nonis, A., Calimeri, T., Perrone, S., Cecchetti, C., Tarantino, V., Steffanoni, S., Foppoli, M., and Ciceri, F.
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Male ,Oncology ,Cancer Research ,Lymphoma ,Salvage therapy ,Angiogenesis Inhibitors ,0302 clinical medicine ,Autologous stem-cell transplantation ,80 and over ,cell of origin ,diffuse large B-cell lymphoma ,immunomodulators ,lenalidomide ,maintenance ,transformed high-grade lymphoma ,Aged, 80 and over ,immunomodulator ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,Diffuse ,Survival Rate ,Local ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,medicine.medical_specialty ,Neutropenia ,Maintenance Chemotherapy ,03 medical and health sciences ,Chemoimmunotherapy ,Internal medicine ,Large B-Cell ,medicine ,Humans ,Autologous transplantation ,Aged ,Follow-Up Studies ,Lenalidomide ,Neoplasm Recurrence, Local ,Salvage Therapy ,Survival rate ,business.industry ,medicine.disease ,Neoplasm Recurrence ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
We report final results of a phase II trial addressing efficacy and feasibility of lenalidomide maintenance in patients with chemosensitive relapse of diffuse large B-cell lymphoma (DLBCL) not eligible for or failed after autologous stem cell transplantation (ASCT). Patients with relapsed DLBCL who achieved at least a partial response to salvage chemoimmunotherapy were enrolled and treated with lenalidomide 25 mg/day for 21 of 28 days for 2 years or until progression or unacceptable toxicity. Primary endpoint was 1-year PFS. Forty-six of 48 enrolled patients were assessable. Most patients had IPI ≥2, advanced stage and extranodal disease before the salvage treatment that led to trial registration; 28 (61%) patients were older than 70 years. Lenalidomide was well tolerated. With the exception of neutropenia, grade-4 toxicities occurred in
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- 2020
16. Caring with compassion during COVID-19
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Mona-Rita Yacoub, Samuele Renzi, Federico Fallanca, Piera Angelillo, Ursola Pajoro, Giovanni Landoni, Gino Pepe, Moreno Tresoldi, Gisella Maestranzi, Alberto Zangrillo, Renzi, Samuele, Fallanca, Federico, Zangrillo, Alberto, Tresoldi, Moreno, Landoni, Giovanni, Angelillo, Piera, Pepe, Gino, Pajoro, Ursola, Maestranzi, Gisella, and Yacoub, Mona-Rita
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Adult ,Male ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Health Personnel ,media_common.quotation_subject ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Compassion ,Betacoronavirus ,Health personnel ,Pandemic ,Humans ,Family ,Burnout, Professional ,Pandemics ,General Nursing ,Aged ,media_common ,Aged, 80 and over ,biology ,SARS-CoV-2 ,COVID-19 ,General Medicine ,Middle Aged ,biology.organism_classification ,Virology ,Psychiatry and Mental health ,Clinical Psychology ,Female ,Empathy ,Coronavirus Infections ,Psychology - Published
- 2020
17. Interleukin-1 receptor-associated kinase 4 inhibitor interrupts toll-like receptor signalling and sensitizes chronic lymphocytic leukaemia cells to apoptosis
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Maria Giovanna Vilia, Maria Elena Mantione, Lydia Scarfò, Alessandra Rovida, Paolo Ghia, Marta Muzio, Ilenia Sana, Vincenza Simona Delvecchio, Piera Angelillo, Pamela Ranghetti, Delvecchio, V. S., Sana, I., Mantione, M. E., Vilia, M. G., Ranghetti, P., Rovida, A., Angelillo, P., Scarfo', L., Ghia, P., and Muzio, M.
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Male ,Apoptosis ,03 medical and health sciences ,chemistry.chemical_compound ,interleukin-1 receptor–associated kinase 4 ,0302 clinical medicine ,Cell surface receptor ,ibrutinib ,hemic and lymphatic diseases ,Bruton's tyrosine kinase ,Humans ,Receptor ,Toll-like receptor ,biology ,Kinase ,Toll-Like Receptors ,fludarabine ,TLR9 ,Hematology ,IRAK4 ,Leukemia, Lymphocytic, Chronic, B-Cell ,Interleukin-1 Receptor-Associated Kinases ,chemistry ,toll-like receptors ,030220 oncology & carcinogenesis ,Ibrutinib ,Cancer research ,biology.protein ,Female ,chronic lymphocytic leukaemia ,030215 immunology ,Signal Transduction - Abstract
Chronic lymphocytic leukaemia (CLL) cells are strongly influenced by microenvironmental signals through the activation of distinct membrane receptors including the B-cell receptor and toll-like receptors (TLR). Recapitulating TLR stimulation in vitro by treating CLL cells with the TLR9 ligand CpG can induce metabolic activation and protection from apoptosis. We hypothesized that interfering with TLR signalling may be beneficial for treating CLL, and we tested in preclinical studies the effect of a specific interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitory small molecule on primary leukaemic cells isolated from the peripheral blood of patients. We observed that IRAK4, an upstream kinase of the TLR pathway, is expressed in patients with CLL, and lower IRAK4 mRNA levels associate with a better outcome. The specific IRAK4 inhibitor disrupted TLR signalling as assessed by reduction of the specific biomarkers NFKBIZ and interleukin-6 mRNAs, and restrained the protective effect of in vitro TLR stimulation on cell viability. To note, IRAK4 inhibitor induced p53 and triggered apoptosis. Co-treatment of CLL cells with increasing concentrations of IRAK4i and the Bruton tyrosine kinase inhibitor ibrutinib demonstrated a synergistic effect. Our results suggest that targetting IRAK4 may represent a novel approach in CLL and may be combined with other signalling inhibitors.
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- 2019
18. Diagnostic and Clinical Impact of Staging
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Domenico, Albano, Paola, Ferro, Giovanni, Bosio, Federico, Fallanca, Alessandro, Re, Alessandra, Tucci, Andrés José, Maria Ferreri, Piera, Angelillo, Luigi, Gianolli, Raffaele, Giubbini, and Francesco, Bertagna
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Adult ,Aged, 80 and over ,Male ,Lymphoma, Mantle-Cell ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Survival Rate ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Radiopharmaceuticals ,Aged ,Follow-Up Studies ,Retrospective Studies ,Stem Cell Transplantation - Abstract
The diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (One hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ.All patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2.
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- 2019
19. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101
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Simona Piemontese, Fabio Ciceri, Antonio M. Risitano, Cecilia Garlanda, Piera Angelillo, Annalisa Ruggeri, Dimitrios C. Mastellos, Despina Yancopoulou, Sara Mastaglio, Markus Huber-Lang, Andrea Assanelli, John D. Lambris, Mastaglio, S., Ruggeri, A., Risitano, A. M., Angelillo, P., Yancopoulou, D., Mastellos, D. C., Huber-Lang, M., Piemontese, S., Assanelli, A., Garlanda, C., Lambris, J. D., and Ciceri, F.
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Male ,0301 basic medicine ,ARDS ,Hypercholesterolemia ,Pneumonia, Viral ,Immunology ,Lung injury ,Antiviral Agents ,Peptides, Cyclic ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Atrial Fibrillation ,medicine ,Humans ,Immunology and Allergy ,Complement Activation ,Lung ,Pandemics ,Aged ,Antiviral Agent ,Innate immune system ,Betacoronaviru ,Pandemic ,Coronavirus Infection ,SARS-CoV-2 ,business.industry ,Effector ,Mechanism (biology) ,COVID-19 ,Complement C3 ,medicine.disease ,Complement (complexity) ,Pneumonia ,Complement Inactivating Agent ,Complement Inactivating Agents ,Treatment Outcome ,030104 developmental biology ,Hypertension ,Coronavirus Infections ,business ,Cytokine storm ,Human ,030215 immunology - Abstract
Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a “cytokine storm” involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.
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- 2020
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20. LONG-TERM EFFICACY AND SAFETY OF LENALIDOMIDE MAINTENANCE IN PATIENTS WITH RELAPSED DIFFUSE LARGE B-CELL LYMPHOMA WHO ARE NOT ELIGIBLE FOR AUTOLOGOUS TRANSPLANTATION (ASCT)
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M. Ponzoni, Salvatore Perrone, Piera Angelillo, Annalisa Arcari, C. Rusconi, Caterina Stelitano, Alberto Fabbri, Fabio Ciceri, Maurizio Frezzato, Alessandro Re, Anna Ferreri, Francesco Zaja, A. Di Rocco, T. Calimeri, Michele Spina, Renato Zambello, Marianna Sassone, C. Cecchetti, D. De Lorenzo, Giovanni Bertoldero, and Stefano Volpetti
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Internal medicine ,medicine ,Autologous transplantation ,In patient ,business ,Diffuse large B-cell lymphoma ,Lenalidomide ,medicine.drug - Published
- 2019
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21. Is chemotherapy really the best option in older adults with acute myeloid leukemia?
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Felicetto Ferrara, Cira Riccardi, Piera Angelillo, and Antonella Carbone
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medicine.medical_specialty ,Chemotherapy ,Hematology ,business.industry ,medicine.medical_treatment ,Intensive treatment ,Myeloid leukemia ,Disease ,Oncology ,Older patients ,Internal medicine ,medicine ,Pharmacology (medical) ,In patient ,Medical diagnosis ,Intensive care medicine ,business - Abstract
“…more than half of acute myeloid leukemia diagnoses are made in patients older than 65 years … therefore treatment of the disease in advanced age represents a daily challenge in clinical hematology … A major dilemma in older patients is whether or not an intensive treatment approach should be offered.”
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- 2013
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22. Multicenter Phase II Trial Addressing Lenalidomide Maintenance in Patients with Relapsed Diffuse Large B-Cell Lymphoma (rDLBCL) Who Are Not Eligible for Autologous Stem Cell Transplantation (ASCT): Efficacy and Safety Results after a Median Follow-up of Five Years
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Stefano Volpetti, Marianna Sassone, Francesco Zaja, Fabio Ciceri, Piera Angelillo, Giovanni Bertoldero, Alice Di Rocco, Andrés J.M. Ferreri, Annalisa Arcari, Maurizio Frezzato, Alberto Fabbri, Daniela De Lorenzo, Salvatore Perrone, Teresa Calimeri, Eloise Scarano, Maurilio Ponzoni, Caterina Cecchetti, Michele Spina, Renato Zambello, Chiara Rusconi, Alessandro Re, and Caterina Stelitano
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Salvage therapy ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Biochemistry ,Tolerability ,Median follow-up ,Internal medicine ,Clinical endpoint ,Medicine ,business ,Diffuse large B-cell lymphoma ,Progressive disease ,Lenalidomide ,medicine.drug - Abstract
Background: Lenalidomide (LENA) maintenance is associated with significantly improved outcome in patients (pts) with chemosensitive relapse of DLBCL not eligible for ASCT or experiencing relapse after ASCT. Preliminary results of a multicentre phase II trial (NCT00799513), reported after a median follow-up of 25 months, showed a 1-yr PFS of 70 ± 7% and a 1-yr OS of 81 ± 6%, with good tolerability (Ferreri AJM, et al. Lancet Haematol 2017). However, LENA was ongoing in 41% of pts at time of analysis, and late side effects and events after maintenance completion remained to be defined. Herein, we report efficacy and safety results of the trial after a median follow-up of 56 (range 27-100) months. Methods: HIV-neg pts (age ≥18 ys) with de novo or transformed DLBCL and relapsed disease responsive to conventional rituximab-containing salvage therapy were registered and treated with LENA 25 mg/day for 21 days out of 28, until lymphoma progression or unacceptable toxicity. A protocol amendment in 2015 allowed physicians to interrupt maintenance after a minimum duration of two years. Primary endpoint was 1-year PFS. Simon's two-stage optimal design was used. To demonstrate a 1-yr PFS improvement from 30% (P0) to 50% (P1), 47 pts (one-sided; α 5%; β 80%) were needed. Maintenance would be considered effective if ≥19 pts were progression-free survivors at 1 yr. Cell of origin was assessed by NanoString Technology (n=23) and Hans algorithm (n=39). Results: Between 3/2009 and 12/2015, we recruited 48 pts; 46 of them were assessable (median age 72 ys; range 34-86); 36 pts had de novo DLBCL, 10 had transformed DLBCL. All pts were previously treated with anthracycline- and rituximab-based combination, plus ASCT in 6 pts. Thirty-three pts were enrolled at 1st relapse; salvage therapy contained high doses of cytarabine or ifosfamide in two-thirds of cases, and response was complete in 26 pts and partial in 20. Most pts had unfavourable features: IPI ≥2 in 38 (83%) pts, advanced stage in 35 (76%), extranodal disease in 29 (63%), high LDH level in 21 (46%); 28 (61%) pts were older than 70 ys. Sixteen pts received ≥2 years of LENA (5 received >2 ys), 30 pts interrupted treatment due to progressive disease (PD; n= 17), toxicity (9) or pt refusal (4) (Table). LENA was well tolerated after an average of 18 courses/pt (range 3-82). With the exception of neutropenia, grade-4 toxicities occurred in At one year from trial registration, 31 pts were still progression free, which was significantly higher than the pre-determined efficacy threshold (n≥19). During the whole observation period, there were 24 events: progressive disease in 21 pts and death of toxicity in 3, with a 1-yr (primary endpoint) and 5-yr PFS of 67 ± 7% and 50 ± 7%, respectively. The duration of response to LENA was longer than response duration after the prior treatment line in 28 (61%) pts, and was twice as long in 21 (46%) of them. Twenty-six pts were disease-free at the last LENA course (Table), 22 of them remain relapse free after a median observation period from maintenance completion of 26 (8-92) months; 3 of the 4 relapses occurred in pts who received The benefit of LENA was observed both in pts with de novo or transformed DLBCL. According to the Hans' algorithm, the 4-yr PFS was 50 ± 11% for GCB-DLBCL and 42 ± 11% for nonGCB-DLBCL (p= 0.58). Results using the Nanostring technique were consistent with the Hans' algorithm. Overall, 28 (61%) pts are alive, with a 1- and 5-yr OS of 80 ± 6% and 60 ± 8%, respectively. Conclusions: Long-term results of this trial soundly promotes the use of LENA maintenance in pts with chemosensitive relapse of DLBCL not eligible for ASCT or experiencing relapse after ASCT. LENA was well tolerated in this elderly population, without higher toxicity rates in pts treated for ≥2 years, and with enhanced survival figures. These results warrant further investigation of immunomodulatory drugs as maintenance in these high-risk pts. Table. Table. Disclosures Ferreri: Celgene: Research Funding. Zaja:Abbvie: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria; Janssen: Honoraria; Sandoz: Honoraria. Di Rocco:Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Rusconi:Celgene: Research Funding.
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- 2018
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23. Prognostic Impact of 3q21 and 3q26 Cytogenetic Abnormalities in Acute Myeloid Leukemia
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Laura Vicari, Clelia Criscuolo, Felicetto Ferrara, Piera Angelillo, and Mario Annunziata
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Chromosome 7 (human) ,medicine.medical_specialty ,Monosomy ,Thrombocytosis ,business.industry ,Immunology ,Induction chemotherapy ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Surgery ,Transplantation ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,Chromosome abnormality ,business ,Survival analysis - Abstract
Abstract 2594 Background: Abnormalities affecting long arm of chromosome 3 are rare but recurrent in Acute Myeloid Leukemia (AML) and are detected in a variable percentage of AML patients according to different series. The 2008 World Health Organization classification recognizes AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) as a distinct subtype characterized by a poor prognosis. Allogeneic stem cell transplantation seems to improve outcome in eligible patients with these aberrations. Inappropriate expression of the ecotropic viral integration site 1 (EVI1) was demonstrated in virtually all patients with t(3;3)(q21;q26.2) and inv(3)(q21q26.2); as well as in a majority of patients with other 3q26 rearrangements. Other chromosome 3 abnormalities are rarely recognized in AML patients; clinical and prognostic relevance of these alterations is not yet defined. The aim of this study is to assess the prognostic impact of chromosome 3 abnormalities on disease characteristics and treatment outcome in AML. Patients and methods: A total of 580 consecutive adult patients were diagnosed with AML at our institution between February 2002 and July 2012. Conventional cytogenetic analysis performed on diagnostic bone marrow samples detected the presence of 3q abnormalities in 16 patients (2.7%). Two patients were lost to follow-up and were not evaluated for survival analysis. Molecular status of FLT3 and NPM1 was also performed and results are available for 10 patients. Median follow-up time for patients in this series was 47 months ( range 6–125). Results: There were 10 male and 6 female patients, the median age being 64.5 years (range 33–81), 10 patients had de novo AML while 6 evolved from a previously diagnosed myelodysplastic syndrome (MDS). Karyotype from MDS phase was available in 2 patients; both acquired 3q rearrangement at time of progression to AML. At time of diagnosis median haemoglobin value was 9.0 g/dL (range 4–11); median leucocyte count was 10.5 × 103̂/L (range 2.3 – 431). Median platelet count was 116 × 109̂/L (range 28 – 529), consistently with previous studies, which have shown that these patients present with higher platelet count at diagnosis when compared with no 3q rearranged ones. Regarding cytogenetic features 3 patients had t(3;3)(q21;q26), 3 patients had inv(3) (q21; q26), 3 patients showed a balanced rearrangement involving 3q26, while 6 patients harbored a del3q. One patient showed monosomy 3. Additional chromosomal changes were demonstrated in 5 patients, two of them had a complex karyotype (see Table 1), 3 had a monosomy 7. Thirteen patients out of 14 received intensive induction chemotherapy; complete remission (CR) was achieved in 5 patients (CR rate: 35.7%), the remaining 7 patients were resistant to induction as well as to salvage chemotherapy. Four patients underwent autologous stem cell transplantation. Median overall survival in this series is 5.5 months (range 0 – 20). At present only one patient is still alive and in CR, 20 months after diagnosis. Median disease free survival (DFS) for patients achieving a CR was 9 months (range 6–20). Median overall survival for patients resistant to first-line therapy was 3 months (range 0–6). Clinical features and treatment outcome of the patients are summarized in Table 1. Conclusions: The incidence of 3q abnormalities in our single institution series is 2.4%, in keeping with previous studies. Our findings confirm the association between these alterations and thrombocytosis at diagnosis, preceding MDS or multilineage dysplasia, presence in all FAB subtypes (except M3), association with additional chromosomal abnormalities as well as the poor response to conventional chemotherapy (CR rate 35.7%), and very short DFS in spite of obtaining CR. Disclosures: No relevant conflicts of interest to declare.
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- 2012
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