117 results on '"Chiara Pagani"'
Search Results
2. S221: LONG-TERM RESULTS OF THE FIL MCL0208 TRIAL COMPARING LENALIDOMIDE MAINTENANCE (LEN) VS OBSERVATION (OBS) AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) IN MANTLE CELL LYMPHOMA (MCL)
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Marco Ladetto, Rita Tavarozzi, Andrea Evangelista, Elisa Genuardi, Daniela Drandi, Michael Mian, Manuela Zanni, Federica Cavallo, Alice DI Rocco, Vittorio Stefoni, Chiara Pagani, Alessandro Re, Annalisa Chiappella, Monica Balzarotti, Vittorio Ruggero Zilioli, Maria Gomes Da Silva, Luca Arcaini, Annalia Molinari, Filippo Ballerini, Andrés José María Ferreri, Fabio Benedetti, Piero Maria Stefani, Benedetta Puccini, Caterina Stelitano, Elisa Bossi, Mario Luppi, Giovannino Ciccone, Umberto Vitolo, Maurizio Martelli, Simone Ferrero, and Sergio Cortelazzo
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. P1070: DECISIONAL ROLE OF INTERIM PET IN RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA TREATED WITH BEGEV CHEMOTHERAPY AS FIRST SALVAGE
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Chiara Rusconi, Francesca Ricci, Rosa Daffini, Beatrice Casadei, Vittorio Ruggero Zilioli, Federico Mazzon, Vincenzo Marasco, Eleonora Calabretta, Chiara Pagani, Lisa Argnani, Cristina Muzi, Anna Guidetti, Marcello Rodari, Angela Passi, Sara Iadecola, Roberto Cairoli, Pier Luigi Zinzani, Alessandro Re, Paolo Corradini, and Armando Santoro
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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4. P1538: MULTIDRUG RESISTANT BACTERIAL COLONIZATION AND RELATED BLOODSTREAM INFECTIONS IN FEBRILE HAEMATOLOGIC PATIENTS: EPIDEMIOLOGY AND OUTCOME
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Chiara Cattaneo, Lorenzo Masina, Chiara Pagani, Samuele Bagnasco, Francesca Castagna, Federica Colnaghi, Angelica Spolzino, Elisa Cerqui, Nicola Bianchetti, Chiara Bottelli, Margherita Oberti, Erika Borlenghi, Giuseppe Rossi, and Alessandra Tucci
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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5. Role of Rituximab Addition to First-line Chemotherapy Regimens in Nodular Lymphocyte-predominant Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi
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Manuel Gotti, Roberta Sciarra, Alessandro Pulsoni, Francesco Merli, Stefano Luminari, Caterina Zerbi, Livio Trentin, Alessandro Re, Chiara Rusconi, Simonetta Viviani, Andrea Rossi, Federica Cocito, Barbara Botto, Erika Meli, Antonello Pinto, Irene Dogliotti, Guido Gini, Benedetta Puccini, Francesca Ricci, Luca Nassi, Alberto Fabbri, Anna Marina Liberati, Michele Merli, Andrea Riccardo Filippi, Maurizio Bonfichi, Valentina Zoboli, Germana Tartaglia, Giorgia Annechini, Gianna Maria D’Elia, Ilaria Del Giudice, Isabel Alvarez, Andrea Visentin, Stefano Pravato, Daniela Dalceggio, Chiara Pagani, Silvia Ferrari, Caterina Cristinelli, Tanja Lazic, Virginia Valeria Ferretti, Umberto Ricardi, and Luca Arcaini
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite widespread, is not completely elucidated. We retrospectively analyzed baseline characteristics of 308 consecutive patients with NLPHL diagnosed in 19 Italian centers from 2000 to 2018. With a median follow-up of 8.4 years (interquartile range: 4.5–12.4) for treated patients, median overall survival (OS) was not reached and estimated 5-year OS was 97.8% and 5-year progression-free survival (PFS) was 84.5%. Five-year cumulative incidence of histological transformation was 1.4%, 95% confidence interval (CI), 0.5%-3.8%. After adjusting for lymphocyte count, splenic involvement, bulky disease and B symptoms (fever, drenching night sweats, unintentional loss >10% of body weight within the preceding 6 months), patients with stage II or more showed superior PFS with immunochemotherapy in comparison to chemotherapy alone (hazard ratio = 0.4, 95% CI, 0.2-0.8; P = 0.015). Our data suggest an advantage of the use of rituximab combined with chemotherapy ± radiotherapy in the treatment of stage II–III–IV NLPHL.
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- 2023
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6. Diffuse large B-cell lymphoma in octogenarians aged 85 and older can benefit from treatment with curative intent: a report on 129 patients prospectively registered in the Elderly Project of the Fondazione Italiana Linfomi (FIL)
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Alessandra Tucci, Francesco Merli, Alberto Fabbri, Luigi Marcheselli, Chiara Pagani, Benedetta Puccini, Dario Marino, Manuela Zanni, Elsa Pennese, Leonardo Flenghi, Annalisa Arcari, Barbara Botto, Melania Celli, Caterina Mammi, Alessandro Re, Giulia Campostrini, Agostino Tafuri, Vittorio R. Zilioli, Emanuele Cencini, Roberto Sartori, Chiara Bottelli, Michele Merli, Luigi Petrucci, Guido Gini, Monica Balzarotti, Federica Cavallo, Gerardo Musuraca, Stefano Luminari, Giuseppe Rossi, and Michele Spina
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians [LO]) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P
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- 2022
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7. Current Treatment Options and the Role of Functional Status Assessment in Classical Hodgkin Lymphoma in Older Adults: A Review
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Vittorio Ruggero Zilioli, Cristina Muzi, Chiara Pagani, Emanuele Ravano, Erika Meli, Rosa Daffini, Erika Ravelli, Roberto Cairoli, and Alessandro Re
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Hodgkin lymphoma ,elderly ,comorbidity ,functional status ,geriatric assessment ,brentuximab vedotin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Along with the fact that classical Hodgkin lymphoma (cHL) in older adults is frequently considered biologically different from cHL in younger patients, its most distinctive feature is its dismal clinical outcome due to the decreased effectiveness and greater toxicity of therapies. Although strategies to mitigate specific toxicities (e.g., cardiological and pulmonary) have obtained some results, in general, reduced-intensity schemes, proposed as an alternative to ABVD, have proved to be less effective. The addition of brentuximab vedotin (BV) to AVD, especially in a sequential scheme, has demonstrated good efficacy. However, the problem of toxicity persists even with this new therapeutic combination, with comorbidities remaining an important prognostic factor. The adequate stratification of functional status is necessary to distinguish between those patients who will benefit from full treatment and those who will benefit from alternative strategies. A simplified geriatric assessment based on the determination of ADL (activity of daily living), IADL (instrumental ADL), and CIRS-G (Cumulative Illness Rating Scale—Geriatric) scores is an easy-to-use tool that permits adequate patient stratification. Other factors of considerable impact on functional status such as sarcopenia and immunosenescence are currently being studied. A fitness-based treatment choice would also be very useful for relapsed or refractory patients, a more frequent and challenging situation than that is found in young cHL patients.
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- 2023
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8. Prognostic Relevance of NPM1 and FLT3 Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience
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Erika Borlenghi, Chiara Cattaneo, Diego Bertoli, Elisa Cerqui, Silvana Archetti, Angela Passi, Margherita Oberti, Tatiana Zollner, Carlotta Giupponi, Chiara Pagani, Nicola Bianchetti, Chiara Bottelli, Samuele Bagnasco, Margherita Sciumè, Alessandra Tucci, and Giuseppe Rossi
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acute myeloid leukaemia ,high dose cytarabine (HD-ARAC) ,idarubicin ,FLT3 mutation ,NPM1 mutation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly NPM1 and FLT3-ITD mutations. The targeted drugs’ availability has renewed interest in FLT3 mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15–74) carrying the FLT3 (ITD or TKD) and/or NPM1 mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the NPM1-mutated (CR 93.9%, p: 0.0001; survival 71% +/− 6, p: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, p: 0.0009), and the 3 years-relapse-free survival worse (24%, p: NPM1-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in NPM1-mutated patients both with the FLT3 wild-type and mutated AML, while in the NPM1 wild-type and FLT3-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.
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- 2022
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9. An increase in MYC copy number has a progressive negative prognostic impact in patients with diffuse large B-cell and high-grade lymphoma, who may benefit from intensified treatment regimens
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Francesca Schieppati, Piera Balzarini, Simona Fisogni, Alessandro Re, Chiara Pagani, Nicola Bianchetti, Lorenzo Micheli, Angela Passi, Samantha Ferrari, Adriana Maifredi, Chiara Bottelli, Rossella Leopaldo, Vilma Pellegrini, Fabio Facchetti, Giuseppe Rossi, and Alessandra Tucci
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
MYC translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of MYC have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of MYC increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for MYC, BCL2, and BCL6 rearrangements. We enumerated the number of MYC copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of MYC translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with MYC copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of MYC extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of MYC had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with MYC translocation. The survival of patients with >4 copies, translocation or amplification of MYC seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence in situ hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of MYC.
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- 2020
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10. Isavuconazole in Hematological Patients: Results of a Real-Life Multicentre Observational Seifem Study
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Chiara Cattaneo, Alessandro Busca, Doriana Gramegna, Francesca Farina, Anna Candoni, Monica Piedimonte, Nicola Fracchiolla, Chiara Pagani, Maria Ilaria Del Principe, Maria Chiara Tisi, Massimo Offidani, Rosa Fanci, Stelvio Ballanti, Angelica Spolzino, Marianna Criscuolo, Francesco Marchesi, Gianpaolo Nadali, Mario Delia, Marco Picardi, Margherita Sciumé, Valentina Mancini, Attilio Olivieri, Mario Tumbarello, Giuseppe Rossi, and Livio Pagano
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract. Invasive fungal diseases (IFDs) remain a major clinical issue in patients with hematological malignancies (HMs). To confirm the efficacy and safety of the new azole isavuconazole (ISV) in a clinical care setting, we planned a multicenter retrospective study; we collected data on all possible/probable/proven IFDs in patients with HMs treated with ISV in 17 centers. Between July 2016 and November 2018, 128 patients were enrolled, and 122 were fully evaluable. ISV was employed as the 1st line therapy in 43 (35%) patients and as a subsequent therapy in 79 (65%) patients. The response rate was 82/122 patients (67.2%); it was similar when using ISV as a 1st or 2nd line treatment (60.5% vs 70.9%, respectively; p = 0.24). In multivariate analysis, both female sex (OR: 2.992; CI: 1.22–7.34) and induction phase of treatment (OR: 3.953; CI: 1.085–14.403) were predictive of a favorable response. At a median follow-up of 5 months, 43 (35.2%) patients were dead; the 1-year overall survival (OS) was 49.9%. In multivariate analysis, the response to ISV (OR: 0.103; CI: 0.041–0.262) and IFD refractoriness to previous antifungals (OR: 3.413; CI: 1.318–8.838) were statistically significant for OS. Adverse events (AEs) were reported in 15/122 patients (12.3%); grade 3–4 AEs were reported in 5 (4%) and led to ISV discontinuation. Our study confirms the safety and tolerability of ISV, also in diseases other than acute leukemia. Phase of hematological disease, gender and refractoriness to previous antifungals are the main predictive factors for the aforementioned response and outcome.
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- 2019
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11. High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program
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Tamara Intermesoli, Alessandro Rambaldi, Giuseppe Rossi, Federica Delaini, Claudio Romani, Enrico Maria Pogliani, Chiara Pagani, Emanuele Angelucci, Elisabetta Terruzzi, Alessandro Levis, Vincenzo Cassibba, Daniele Mattei, Giacomo Gianfaldoni, Anna Maria Scattolin, Eros Di Bona, Elena Oldani, Margherita Parolini, Nicola Gökbuget, and Renato Bassan
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
We evaluate the long-term results of a prospective clinical study enrolling more than 100 adult patients with Burkitt lymphoma/leukemia. Depending on extent of disease, treatment consisted of six to eight rituximab infusions and four to six courses of intensive chemotherapy (attenuated in patients aged >55 years) with high-dose methotrexate, fractionated ifosfamide/cyclophosphamide, other drugs in rotation, and intrathecal chemoprophylaxis. One-hundred five patients were treated (median age 47 years, range 17–78 years); 48% had Burkitt leukemia, 25% were older than 60 years, 37% had an Eastern Cooperative Oncology Group performance score >1, and 14% were positive for human immunodeficiency virus. The complete response rate and 3-year overall and disease-free survival rates were 79%, 67% and 75%, respectively, ranging from 100% to 45% for survival (P=0.000) and from 100% to 60% for disease-free survival (P=0.01) in patients with low, intermediate and high adapted International Prognostic Index scores. In multivariate analysis, only age (≤ versus >60 years) and performance status (0–1 versus >1) retained prognostic significance, identifying three risk groups with overall and disease-free survival probabilities of 88% and 87.5%, 57% and 70.5%, 20% and 28.5% (P=0.0000 and P=0.0001), respectively. The relapse rate was only 7% in patients treated with an intercycle interval ≤25 days. This regimen achieved 100% curability in patients with low adapted International Prognostic Index scores (21% of total), and very close to 90% in patients aged ≤60 years with performance score 0–1 (48% of total). Rapid diagnosis of Burkitt lymphoma/leukemia with prompt referral of patients to prevent clinical deterioration, and careful supervision of treatment without chemotherapy delay can achieve outstanding therapeutic results. ClinicalTrials.gov ID, NCT01290120
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- 2013
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12. 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
13. Not Yet Time to Retire Splenectomy in Splenic Marginal Zone Lymphoma (SMZL): Results of a Single Center Experience
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Antonella Anastasia, Chiara Pagani, Alessandro Re, Marina Motta, Giacomo Pata, Enrico Damiani, Lisa Gandolfi, Rosa Daffini, and Alessandra Tucci
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
14. Prognostic Relevance of
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Erika, Borlenghi, Chiara, Cattaneo, Diego, Bertoli, Elisa, Cerqui, Silvana, Archetti, Angela, Passi, Margherita, Oberti, Tatiana, Zollner, Carlotta, Giupponi, Chiara, Pagani, Nicola, Bianchetti, Chiara, Bottelli, Samuele, Bagnasco, Margherita, Sciumè, Alessandra, Tucci, and Giuseppe, Rossi
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The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly
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- 2022
15. High mortality in fully vaccinated hematologic patients treated with anti-CD20 antibodies during the 'Omicron wave' of COVID-19 pandemic
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Chiara Cattaneo, Lorenzo Masina, Chiara Pagani, Valeria Cancelli, Rosa Daffini, Alessandra Tucci, and Giuseppe Rossi
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Cancer Research ,Oncology ,Hematology ,General Medicine - Published
- 2022
16. Validation of the 'fitness criteria' for the treatment of older patients with acute myeloid leukemia: A multicenter study on a series of 699 patients by the Network Rete Ematologica Lombarda (REL)
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Chiara Pagani, Erika Borlenghi, Matteo Claudio Da Via, Chiara Cattaneo, Fabio Ciceri, Roberto Cairoli, Francesco Passamonti, Massimo Bernardi, Claudia Basilico, Nicola Stefano Fracchiolla, Valentina Mancini, Mauro Turrini, Mariarita Sciumè, Elisabetta Todisco, Giuseppe Rossi, Patrizia Zappasodi, Elisa Cerqui, Margherita Sciumé, Borlenghi, E, Pagani, C, Zappasodi, P, Bernardi, M, Basilico, C, Cairoli, R, Fracchiolla, N, Todisco, E, Turrini, M, Cattaneo, C, Da Via, M, Ciceri, F, Passamonti, F, Mancini, V, Sciume, M, Cerqui, E, and Rossi, G
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medicine.medical_specialty ,Multivariate analysis ,Fitne ,Concordance ,Karyotype ,Comorbidity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Fitness ,medicine ,Humans ,030212 general & internal medicine ,Exercise ,Aged ,Retrospective Studies ,Acute myeloid leukemia ,Performance status ,business.industry ,Older ,Treatment ,Myeloid leukemia ,Retrospective cohort study ,medicine.disease ,Clinical trial ,Leukemia, Myeloid, Acute ,Leukemia ,Oncology ,030220 oncology & carcinogenesis ,Geriatrics and Gerontology ,business - Abstract
Objectives: Treatment of older patients with acute myeloid leukemia (AML) is still controversial. To facilitate treatment decisions, the “fitness criteria” proposed by Ferrara et al. (Leukemia, 2013), including age > 75 years, performance status and comorbidities, were verified retrospectively in 699 patients with AML (419 de-novo, 280 secondary AML), diagnosed at 8 Hematological Centers (REL). Methods: Patients were categorized in FIT to intensive chemotherapy (i-T) (292, 42.5%), UNFIT to i-T (289, 42.1%), or unfit even to non-intensive therapy (non i-T) (FRAIL) (105, 15.3%). Biological characteristics and treatment actually received by patients [i-T, 274 patients (39.2%); non i-T, 134 (19.2%), best-supportive care (BSC), 291 (41.6%)] were recorded. Results: “Fitness criteria” were easily applicable in 98.1% of patients. Overall concordance between “fitness criteria” and treatment actually received by patients was high (79.4%), 76% in FIT, 82.7% in UNFIT and 80% in FRAIL patients. Fitness independently predicted survival (median survival: 10.9, 4.2 and 1.8 months in FIT, UNFIT and FRAIL patients, respectively; p = 0.000), as confirmed also by multivariate analysis. In FRAIL patients, survival with any treatment was no better than with BSC, in UNFIT non i-T was as effective as i-T and better than BSC, and in FIT patients i-T was better than non i-T or BSC. In addition, a non-adverse risk AML, an ECOG PS
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- 2021
17. Adhesive capsulitis after COVID-19 vaccine injection: a peculiar case treated with combined bursa distention and glenohumeral capsular hydrodilatation
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Alessandro Biglia, Valentina Morandi, Giovanni Zanframundo, Danilo Donati, Francesco Maggiore, Fabio Vita, Luigi Sammarchi, Chiara Pagani, Lorenzo Cavagna, Stefano Galletti, and Carlomaurizio Montecucco
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Internal Medicine ,Radiology, Nuclear Medicine and imaging ,General Medicine - Abstract
Frozen shoulder is a common and self-limiting condition affecting the soft tissues of the shoulders, characterized by severe pain, impaired range of motion (ROM) and limitation of daily activities. Its prevalence is 5% and it occurs most commonly in the fifth and sixth decades of life; women are more affected [DePalma in Clin Orthop Relat Res 466:552–560, 2008]. It can be idiopathic or associated with other conditions such as metabolic disorders, diabetes, thyroid diseases, prolonged immobilization, trauma [DePalma in Clin Orthop Relat Res 466:552–560, 2008], or complications after vaccine administration known as SIRVA (Shoulder injury related to vaccine administration). SIRVA is not caused by the vaccine itself but by inappropriate vaccination techniques [Martín Arias et al. in Vaccine 35:4870–4876, 2017]. The natural history of the frozen shoulder is a progression through three stages based on clinical and arthroscopic presentations: freezing, frozen and thawing [DePalma in Clin Orthop Relat Res 466:552–560, 2008; Do et al. in Orthop J Sport Med 9:232596712110036, 2021]. The onset is characterized by disabling pain, that worsens at night; it is induced by inflammation and hypervascularity and lasts from 10 to 36 weeks [Do et al. in Orthop J Sport Med 9:232596712110036, 2021]. The second stage is predominated by stiffness and severe reduction of ROM. This phase typically lasts from 9 to 12 months [Do et al. in Orthop J Sport Med 9:232596712110036, 2021]. Eventually, a recovery phase occurs, with a gradual recovery of the ROM that can last between 12 and 42 months. Ultrasound is an emerging diagnostic tool that contributes to differential diagnosis and treatment [Zappia et al. in Insights Imaging 7:365–371, 2016; Ricci et al. in J Ultrasound Med 39:633–635, 2020]: signs of adhesive capsulitis consist of thickening of the inferior recess of the glenohumeral joint capsule, thickening of the coracohumeral ligament and soft tissue structures in the rotator cuff interval, with hypervascularity. An unspecific sign is increased fluid in the tendon sheath of the long head of the biceps [Martín Arias et al. in Vaccine 35:4870–4876, 2017; Tandon et al. in J Ultrasound 20:227–236, 2017].
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- 2022
18. Author response for 'High mortality in fully vaccinated hematologic patients treated with anti‐CD20 antibodies during the 'Omicron wave' of COVID‐19 pandemic'
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null Chiara Cattaneo, null Lorenzo Masina, null Chiara Pagani, null Valeria Cancelli, null Rosa Daffini, null Alessandra Tucci, and null Giuseppe Rossi
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- 2022
19. 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
20. Postremission therapy with repeated courses of high‐dose cytarabine, idarubicin, and limited autologous stem cell support achieves a very good long‐term outcome in European leukemia net favorable and intermediate‐risk acute myeloid leukemia
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Doriana Gramegna, Chiara Pagani, Angela Passi, Erika Borlenghi, Chiara Cattaneo, Claudia Crippa, Francesca Schieppati, Margherita Oberti, Daniela Bellotti, Margherita Sciumé, Elisa Cerqui, Cecilia Carbone, Daniela Dalceggio, Giuseppe Rossi, Diego Bertoli, Mirko Farina, Alessandra Tucci, Silvana Archetti, and Giulia Soverini
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Myeloid ,Male ,Oncology ,Cancer Research ,medicine.medical_treatment ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Leukemia ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Induction Chemotherapy ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Toxicity ,outcome ,Female ,Stem cell ,Autologous ,medicine.drug ,acute myeloid leukemia ,consolidation ,high dose cytarabine (HDAC) ,Adult ,Aged ,Daunorubicin ,Humans ,Survival Analysis ,Transplantation, Autologous ,Young Adult ,medicine.medical_specialty ,Acute ,03 medical and health sciences ,Refractory ,Internal medicine ,Idarubicin ,Transplantation ,Chemotherapy ,business.industry ,medicine.disease ,business ,030215 immunology - Abstract
Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High-dose cytarabine (HDAC) is considered first choice in favorable risk and an option in intermediate-risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long-term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML-01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high-risk AML (adverse cytogenetic, isolated FLT3-internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19-75), were considered standard-risk and received the NILG AML-01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+-PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1-2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment-related mortality was 3/160 (1.8%). After a median follow-up of 66.4 months, overall survival (OS) and relapse-free survival (RFS) at 5-years were 61.4% and 52.4%, respectively. Twenty-eight selected patients aged >65 had similar outcomes. According to European leukemia net-2010 classification, the OS and RFS at 5-years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate-I, 45.2% and 36.5% in Intermediate-II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis.
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- 2020
21. Clinical and prognostic role of interim 18F-FDG PET/CT in elderly Hodgkin lymphoma: a dual-center experience
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Raffaele Giubbini, Claudio Rossetti, Cristina Muzi, Chiara Pagani, Francesco Bertagna, Domenico Albano, Vittorio Ruggero Zilioli, Alessandro Re, Alessandra Tucci, Lara Crucitti, and Angelica Mazzoletti
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Cancer Research ,elderly ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,immune system diseases ,Interim pet ct ,Positron Emission Tomography Computed Tomography ,hemic and lymphatic diseases ,Interim ,Humans ,Medicine ,interim PET/CT ,Aged ,Retrospective Studies ,business.industry ,18F-FDG PET/CT ,Hematology ,Middle Aged ,Prognosis ,Hodgkin Disease ,Interim pet ,Hodgkin lymphoma ,Oncology ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Age distribution ,Fdg pet ct ,business ,Nuclear medicine ,030215 immunology - Abstract
Hodgkin lymphoma (HL) has a bimodal age distribution curve, with a second peak in people aged more than 60 years. Interim PET/CT (iPET/CT) is highly predictive for PFS and OS in young HL, but it has not been sufficiently studied in the elderly. In this retrospective dual-center study, 82 patients with HL and aged 65 or more who performed iPET/CT were included. At iPET/CT, 60 patients had a complete metabolic response, 18 partial responses, and 4 progressions of disease. Baseline PET/CT metabolic features were not significantly correlated with the metabolic response at interim. In patients with interim complete metabolic response, PFS and OS were significantly longer than in patients without complete response(
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- 2020
22. Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in elderly HL: a two-center experience in 123 patients
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Vittorio Ruggiero Zilioli, Chiara Pagani, Domenico Albano, Angelica Mazzoletti, Marianna Spallino, Raffaele Giubbini, Claudio Rossetti, Alessandra Tucci, Francesco Bertagna, and Cristina Muzi
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Male ,medicine.medical_specialty ,Treatment response ,Aggressive lymphoma ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,Internal medicine ,Tumor stage ,medicine ,Humans ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hematology ,business.industry ,General Medicine ,Prognosis ,Hodgkin Disease ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,Female ,Fdg pet ct ,medicine.symptom ,Nuclear medicine ,business ,030215 immunology - Abstract
Elderly Hodgkin lymphoma (HL) is an aggressive lymphoma subgroup with high 18F-FDG avidity at 18F-FDG-PET/CT but no shared criteria for PET/CT in treatment evaluation and prediction of outcome are available. The aim of our bicentric study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in elderly HL. We retrospectively included 123 patients who underwent baseline 18F-FDG-PET/CT and end of treatment PET/CT scans. The PET images were analyzed visually and semi-quantitatively by measuring the lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan-Meier method. At a median follow-up of 40 months, the median PFS and OS were 29 and 37 months. L-BP SUV R, L-L SUV R, MTV, and TLG were significantly higher in patients with no complete response compared with complete response group at end of treatment. Moreover, these parameters were demonstrated to be independent prognostic factors for PFS together with tumor stage, while only L-L SUV R and L-BP SUV R for OS. End of treatment PET/CT results using Deauville criteria were significantly correlated with outcome survival. End of treatment PET/CT results (using Deauville criteria) and semiquantitative baseline PET/CT parameters were significantly correlated with response to treatment and long-term outcome.
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- 2020
23. Dissecting MRD Kinetics By Automated Computational Analysis to Improve Outcome Prediction in Mantle Cell Lymphoma: A Bioinformatic Substudy from the Fondazione Italiana Linfomi (FIL) MCL0208 Clinical Trial
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Francesca Cordero, Simone Ferrero, Simone Pernice, Elisa Genuardi, Roberta Sirovich, Beatrice Alessandria, Andrea Evangelista, Simone Ragaini, Maurizio Martelli, Alice Di Rocco, Alessandro Re, Chiara Pagani, Vittorio Stefoni, Federica Cavallo, Carola Boccomini, Monica Balzarotti, Vittorio Ruggero Zilioli, Maria Gomes da Silva, Luca Arcaini, Melania Celli, Gian Maria Zaccaria, Dora Tortarolo, Sergio Cortelazzo, and Marco Ladetto
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
24. Production and persistence of specific antibodies in COVID-19 patients with hematologic malignancies: role of rituximab
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Alessandro Re, Giuseppe Rossi, Luigi D. Notarangelo, Angelo Belotti, Valeria Cancelli, Helen C. Su, Jeffrey I. Cohen, A. Anastasia, Luisa Imberti, Virginia Quaresima, Chiara Pagani, Chiara Cattaneo, Alessandra Tucci, Peter D. Burbelo, John A. Chiorini, Kerry Dobbs, and Alessandra Sottini
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Adult ,Male ,medicine.medical_specialty ,Follicular lymphoma ,Lymphoproliferative disorders ,Antibodies, Viral ,Gastroenterology ,Article ,Antibodies ,Antibody Specificity ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,Seroconversion ,Prospective cohort study ,RC254-282 ,Multiple myeloma ,Aged ,Aged, 80 and over ,Haematological cancer ,biology ,SARS-CoV-2 ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,COVID-19 ,Hematology ,Middle Aged ,medicine.disease ,Immunity, Humoral ,Lymphoma ,Hospitalization ,Italy ,Oncology ,Case-Control Studies ,Hematologic Neoplasms ,Antibody Formation ,biology.protein ,Female ,Rituximab ,Antibody ,business ,Follow-Up Studies ,medicine.drug - Abstract
The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.
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- 2021
25. 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
26. AUTOLOGOUS TRANSPLANT IN ELDERLY PATIENTS WITH R/R AGGRESSIVE LYMPHOMA SELECTED BY SIMPLIFIED CGA: THE RECANZ PROSPECTIVE PHASE 2 STUDY BY THE FONDAZIONE ITALIANA LINFOMI
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Monica Tani, Luigi Marcheselli, E. V Liardo, Chiara Pagani, Vittorio Ruggero Zilioli, Manuela Zanni, Francesco Merli, Donato Mannina, Francesca Re, Daniele Vallisa, Alessandra Tucci, Agnese Re, Giulia Campostrini, Daniele Grimaldi, Mariagrazia Michieli, Gerardo Musuraca, Giulio Rossi, Maria Christina Cox, Sabrina Pelliccia, and Federica Cavallo
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Phases of clinical research ,Aggressive lymphoma ,Hematology ,General Medicine ,business ,Autologous transplant - Published
- 2021
27. DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN LATE‐OCTOGENARIAN (LO) PATIENTS: A SUBSTUDY OF THE 'ELDERLY PROJECT' BY THE FONDAZIONE ITALIANA LINFOMI (FIL)
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Alessandra Tucci, R. Sartori, Caterina Mammi, Luigi Marcheselli, Salvatrice Mancuso, Alberto Fabbri, Vittorio Ruggero Zilioli, Stefano Luminari, Benedetta Puccini, Maria Christina Cox, Federica Cavallo, Agnese Re, Sergio Storti, G. Gini, Annalisa Arcari, Chiara Bottelli, Chiara Pagani, Giulio Rossi, Michele Spina, Francesco Merli, and Monica Balzarotti
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Hematology ,General Medicine ,business ,medicine.disease ,Diffuse large B-cell lymphoma - Published
- 2021
28. IMPAIRED HUMORAL RESPONSE IN LYMPHOMA PATIENTS SURVIVING THE ACUTE PHASE OF COVID‐19
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Giulio Rossi, A. Sotttini, Peter D. Burbelo, V. Quaresima, Kerry Dobbs, Chiara Cattaneo, V. Cancelli, Luigi D. Notarangelo, Alessandra Tucci, Chiara Pagani, A. Ogna, and Jeffrey I. Cohen
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Cancer Research ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Hematology ,General Medicine ,medicine.disease ,Virology ,Lymphoma ,E‐posters ,Oncology ,Medicine ,SUPPLEMENT: 16th INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA, VIRTUAL EDITION, 18–22 JUNE, 2021 ,Supplement Abstract ,business - Published
- 2021
29. Reduction in the rate and improvement in the prognosis of COVID-19 in haematological patients over time
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Luigi D. Notarangelo, Chiara Cattaneo, Valeria Cancelli, Aldo M. Roccaro, Giuseppe Rossi, Luisa Imberti, and Chiara Pagani
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Letter ,Coronavirus disease 2019 (COVID-19) ,MEDLINE ,Reduction (complexity) ,Young Adult ,Text mining ,Internal medicine ,medicine ,Humans ,Young adult ,Survival rate ,Aged ,Aged, 80 and over ,Public health ,SARS-CoV-2 ,business.industry ,Follow up studies ,COVID-19 ,Hematology ,Middle Aged ,Prognosis ,Survival Rate ,Oncology ,Hematologic Neoplasms ,Female ,business ,Haematological diseases ,Follow-Up Studies - Published
- 2020
30. An increase in MYC copy number has a progressive negative prognostic impact in patients with diffuse large B-cell and high-grade lymphoma, who may benefit from intensified treatment regimens
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Chiara Pagani, Samantha Ferrari, Francesca Schieppati, Angela Passi, Giuseppe Rossi, Rossella Leopaldo, Alessandro Re, Chiara Bottelli, Fabio Facchetti, Piera Balzarini, Nicola Bianchetti, Lorenzo Micheli, Vilma Pellegrini, Alessandra Tucci, Simona Fisogni, and Adriana Maifredi
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Aggressive Non-Hodgkin's Lymphoma ,Fluorescence in situ hybridization ,MYC gene aberrations ,High-grade lymphoma ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Chromosomal translocation ,Hematology ,BCL6 ,medicine.disease ,Lymphoma ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Cancer research ,Medicine ,business ,Gene ,B cell ,030215 immunology - Abstract
MYC translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of MYC have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of MYC increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for MYC, BCL2, and BCL6 rearrangements. We enumerated the number of MYC copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of MYC translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with MYC copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of MYC extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of MYC had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with MYC translocation. The survival of patients with >4 copies, translocation or amplification of MYC seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence in situ hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of MYC.
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- 2019
31. The e13a2 BCR‐ABL transcript negatively affects sustained deep molecular response and the achievement of treatment‐free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors
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Elisa Cerqui, Alessandra Tucci, Maria A. Capucci, Giuseppina Ruggeri, Samantha Ferrari, Chiara Pagani, Erika Borlenghi, Francesca Schieppati, Chiara Bottelli, Giuseppe Rossi, Doriana Gramegna, Mirko Farina, Angela Passi, Mariella D'Adda, and Adriana Maifredi
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Fusion Proteins, bcr-abl ,Real-Time Polymerase Chain Reaction ,Disease-Free Survival ,Drug Administration Schedule ,Tyrosine-kinase inhibitor ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,Humans ,In patient ,Molecular Targeted Therapy ,030212 general & internal medicine ,Protein Kinase Inhibitors ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,Academic Medical Centers ,Dose-Response Relationship, Drug ,business.industry ,Myeloid leukemia ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,respiratory tract diseases ,Discontinuation ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Molecular Response ,Multivariate Analysis ,Imatinib Mesylate ,Female ,business ,Tyrosine kinase ,Chronic myelogenous leukemia - Abstract
Background Stopping tyrosine kinase inhibitor (TKI) treatment has become a realistic and safe objective for patients who have chronic myeloid leukemia (CML). Both a sustained deep molecular response (sDMR) and the lack of a molecular recurrence after TKI discontinuation are required to reach a durable treatment-free remission (TFR). Methods The potential predictive role of BCR-ABL transcripts in attaining an sDMR and a TFR was analyzed in a strictly consecutive, unselected series of 194 patients who were diagnosed and treated with TKIs at the authors' center. Results Of 173 fully evaluable patients, 67 (38.7%) had the e13a2 transcript, and 106 (61.3%) had the e14a2 transcript. Complete cytogenetic and major molecular remissions were not affected, whereas the achievement of both a DMR (P = .008) and an sDMR (P = .004) was favored significantly in patients who had the e14a2 transcript. After a median of 68 months, the sDMR rate was 39.6% in those with the e14a2 transcript and 19.4% in those with the e13a2 transcript. In addition to transcript type, both the early achievement of a molecular response and starting treatment with a second-generation TKI positively affected the attainment of an sDMR in multivariate analysis. The use of a second-generation TKI as frontline treatment increased the sDMR rate in both transcript types. However, in patients who had the e13a2 transcript, the probability of attaining an sDMR was 37% after 60 months and did not increase further despite continuing therapy. Among 51 of 60 patients who attained an sDMR after discontinuing TKIs, 24 experienced a molecular relapse, but all regained molecular remission after resuming TKI treatment. Again, transcript type influenced TFR maintenance (P = .005), because only 2 patients (3%) with the e13a2 transcript enjoyed a durable TFR compared with 25 (23.5%) of those with the e14a2 transcript. Conclusions The e13a2 transcript hinders the achievement of deep responses and the possibility of stopping TKI treatment in patients with CML.
- Published
- 2019
32. Cant1 Affects Cartilage Proteoglycan Properties: Aggrecan and Decorin Characterization in a Mouse Model of Desbuquois Dysplasia Type 1
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Chiara Gramegna Tota, Alessandra Leone, Asifa Khan, Antonella Forlino, Antonio Rossi, and Chiara Paganini
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cartilage ,chondrocyte ,aggrecan ,decorin ,proteoglycan ,glycosaminoglycan ,Microbiology ,QR1-502 - Abstract
Desbuquois dysplasia type 1 (DBQD1) is a recessive chondrodysplasia caused by mutations in the CANT1 gene, encoding for the Golgi Calcium-Activated Nucleotidase 1 (CANT1). The enzyme hydrolyzes UDP, the by-product of glycosyltransferase reactions, but it might play other roles in different cell types. Using a Cant1 knock-out mouse, we demonstrated that CANT1 is crucial for glycosaminoglycan (GAG) synthesis; however, its impact on the biochemical properties of cartilage proteoglycans remains unknown. Thus, in this work, we characterized decorin and aggrecan from primary chondrocyte cultures and cartilage biopsies of mutant mice at post-natal day 4 by Western blots and further investigated their distribution in the cartilage extracellular matrix (ECM) by immunohistochemistry. We demonstrated that the GAG synthesis defect caused by CANT1 impairment led to the synthesis and secretion of proteoglycans with shorter GAG chains compared with wild-type animals. However, this alteration did not result in the synthesis and secretion of decorin and aggrecan in the unglycanated form. Interestingly, the defect was not cartilage-specific since also skin decorin showed a reduced hydrodynamic size. Finally, immunohistochemical studies in epiphyseal sections of mutant mice demonstrated that the proteoglycan structural defect moderately affected decorin distribution in the ECM.
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- 2024
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33. Author response for 'Post‐remission Therapy with Repeated Courses of High Dose Cytarabine, Idarubicin and Limited Autologous Stem Cell Support Achieves a Very Good Long‐Term Outcome in ELN Favorable and Intermediate‐Risk AML'
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Cecilia Carbone, Chiara Cattaneo, Daniela Bellotti, Elisa Cerqui, Chiara Pagani, Mirko Farina, Erika Borlenghi, Giuseppe Rossi, Francesca Schieppati, Daniela Dalceggio, Giulia Soverini, Angela Passi, Alessandra Tucci, Silvana Archetti, Diego Bertoli, Margherita Oberti, Margherita Sciumé, Doriana Gramegna, and Claudia Crippa
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Oncology ,medicine.medical_specialty ,High dose cytarabine ,business.industry ,Internal medicine ,medicine ,Idarubicin ,Stem cell ,Intermediate risk ,business ,Outcome (game theory) ,Term (time) ,medicine.drug - Published
- 2020
34. Clinical characteristics and risk factors for mortality in hematologic patients affected by COVID‐19
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Angelo Belotti, Mariella D'Adda, Chiara Pagani, Erika Borlenghi, Kordelia Barbullushi, Daniela Dalceggio, Alessandro Re, Annalisa Peli, Aldo M. Roccaro, Nicola Bianchetti, Rosa Daffini, Massimo Salvetti, Giuseppe Rossi, Maria Lorenza Muiesan, Alessandra Tucci, Valeria Cancelli, Margherita Oberti, Anna Paini, Valentina Mancini, Roberto Cairoli, Chiara Cattaneo, Carolina De Ciuceis, Antonella Anastasia, Marina Motta, Cattaneo, C, Daffini, R, Pagani, C, Salvetti, M, Mancini, V, Borlenghi, E, D'Adda, M, Oberti, M, Paini, A, De Ciuceis, C, Barbullushi, K, Cancelli, V, Belotti, A, Re, A, Motta, M, Peli, A, Bianchetti, N, Anastasia, A, Dalceggio, D, Roccaro, A, Tucci, A, Cairoli, R, Muiesan, M, and Rossi, G
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Male ,medicine.medical_specialty ,Cancer Research ,Anemia ,Pneumonia, Viral ,Population ,Disease ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Correspondence ,Epidemiology ,medicine ,Humans ,risk factors ,030212 general & internal medicine ,education ,Pandemics ,Aged ,Retrospective Studies ,coronavirus disease 2019 (COVID-19) ,epidemiology ,hematologic patients ,outcome ,education.field_of_study ,SARS-CoV-2 ,business.industry ,Mortality rate ,COVID-19 ,Respiratory infection ,Cancer ,Prognosis ,medicine.disease ,Survival Rate ,Italy ,Hematologic disease ,risk factor ,Oncology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,hematologic patient ,Female ,Coronavirus Infections ,business ,Follow-Up Studies - Abstract
Background: Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID-19) pandemic. However, there are still few data on COVID-19 occurring in hematologic patients. Methods: One hundred two patients with COVID-19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 seen at 2 hematologic departments located in Lombardy, Italy, during March 2020 were studied. Risk factors for acquiring COVID-19 were analyzed by comparisons of patients with COVID-19 and the standard hematologic population managed at the same institutions in 2019. Thirty-day survival was compared with the survival of matched uninfected control patients with similar hematologic disorders and nonhematologic patients affected by COVID-19. Results: Male sex was significantly more prevalent in patients with COVID-19. The infection occurred across all different types of hematologic disease; however, the risk of acquiring a COVID-19 infection was lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive-related treatments. The 30-day mortality rate was 39.2%, which was higher than the rates for nonhematologic patients with COVID-19 (23.5%; P =.02) and uninfected hematologic controls (3%; P
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- 2020
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35. Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial
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Caterina Stelitano, Benedetta Puccini, Manuela Zanni, Luca Arcaini, Rita Tavarozzi, Michael Mian, Umberto Vitolo, Sergio Cortelazzo, Federica Cavallo, Piero Maria Stefani, Monica Balzarotti, Anna Lia Molinari, Giovannino Ciccone, Chiara Pagani, Maria Gomes da Silva, Alessandro Re, Ivana Casaroli, Maurizio Martelli, Filippo Ballerini, Simone Ferrero, Marco Ladetto, Annalisa Chiappella, Vittorio Stefoni, Vittorio Ruggero Zilioli, Alice Di Rocco, Andrea Evangelista, Franco Narni, Andrés J.M. Ferreri, and Fabio Benedetti
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Adult ,Male ,medicine.medical_specialty ,Vincristine ,Lymphoma ,Adolescent ,Population ,Aged ,Antineoplastic Combined Chemotherapy Protocols ,Cyclophosphamide ,Disease-Free Survival ,Doxorubicin ,Female ,Humans ,Lenalidomide ,Middle Aged ,Platelet Count ,Prednisone ,Rituximab ,Survival Rate ,Transplantation, Autologous ,Hematopoietic Stem Cell Transplantation ,Lymphoma, Mantle-Cell ,Maintenance Chemotherapy ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,education ,Survival rate ,Transplantation ,education.field_of_study ,Performance status ,business.industry ,Hematology ,Mantle-Cell ,medicine.disease ,030220 oncology & carcinogenesis ,Mantle cell lymphoma ,business ,Autologous ,030215 immunology ,medicine.drug - Abstract
Summary Background Fit patients with mantle cell lymphoma aged 18–65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population. Methods This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal. Eligible patients had Ann Arbor stage III or IV treatment-naive mantle cell lymphoma (or stage II plus bulky disease [≥5 cm] or B symptoms), and had evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). Patients were aged 18–59 years with Eastern Cooperative Oncology Group (ECOG) performance status 0–3, or aged 60–65 years with ECOG 0–2. After an optional prephase with vincristine and steroids (intravenous vincristine 1·4 mg/m2 on day 1, oral prednisone 100 mg [total dose] on days 1–5), patients were given three courses of R-CHOP (21-day cycle, intravenous rituximab 375 mg/m2 on day 1; intravenous doxorubicin 50 mg/m2, vincristine 1·4 mg/m2, and cyclophosphamide 750 mg/m2 on day 2; oral prednisone 100 mg/m2 on day 2–6). Patients then received one cycle of high-dose CTX (intravenous cyclophosphamide 4 g/m2 on day 1, intravenous rituximab 375 mg/m2 on day 4). After restaging, patients received two cycles of R-HD-cytarabine (high-dose intravenous cytarabine 2 g/m2 every 12 h on days 1–3, intravenous rituximab 375 mg/m2 on days 4 and 10). Patients with complete remission or partial remission proceeded to autologous HSCT and responding patients (complete remission or partial remission) with haematological recovery were randomly assigned (1:1) to receive 24 courses of oral lenalidomide maintenance (15 mg per day for patients with platelets >100 × 109 cells per L or 10 mg per day for platelets 60–100 × 109 cells per L, days 1–21 every 28 days) for 24 months, or observation. The primary endpoint was progression-free survival, measured in the randomised population. This study is registered with EudraCT (2009–012807–25) and ClinicalTrials.gov ( NCT02354313 ). Findings Between May 4, 2010, and Aug 24, 2015, 303 patients were screened for inclusion and 300 patients were enrolled (median age 57 years, IQR 51–62; 235 [78%] male). 95 patients were excluded before randomisation, mostly due to disease progression, adverse events, and inadequate recovery. 104 patients were randomly assigned to the lenalidomide maintenance group and 101 patients to the observation group. 11 (11%) of 104 patients assigned to lenalidomide did not start treatment (3 withdrew, 6 adverse events or protocol breach, 2 lost to follow-up). At a median follow-up of 38 months after randomisation (IQR 24–50), 3-year progression-free survival was 80% (95% CI 70–87) in the lenalidomide group versus 64% (53–73) in the observation group (log-rank test p=0·012; hazard ratio 0·51, 95% CI 0·30–0·87). 41 (39%) of 104 patients discontinued lenalidomide for reasons including death or progression. Treatment-related deaths were recorded in two (2%) of 93 patients in the lenalidomide group (1 pneumonia, 1 thrombotic thrombocytopenic purpura), and one (1%) of 101 in the observation group (pneumonia). 59 (63%) of 93 patients in the lenalidomide group had grade 3–4 haematological adverse events versus 12 (12%) of 101 patients in the observation group (p Interpretation Despite non-negligibile toxicity, lenalidomide after autologous HSCT improved progression-free survival in patients with mantle cell lymphoma, highlighting the role of maintenance in mantle cell lymphoma. Funding Fondazione Italiana Linfomi and Celgene.
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- 2020
36. The classic prognostic factors in advanced Hodgkin’s lymphoma patients are losing their meaning at the time of Pet-guided treatments
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Luca Nassi, Anna Lia Molinari, Monica Tani, Pier Luigi Zinzani, Maurizio Bonfichi, Benedetta Puccini, Daniela Gioia, Alessandro Re, Alessandro Levis, Alessandro Pulsoni, Stefano Sacchi, Alessia Bari, Alessandra Tucci, Erika Meli, Chiara Pagani, Vincenzo Pavone, Raffaella Marcheselli, Umberto Vitolo, Andrea Evangelista, Barbara Botto, Armando Santoro, Bari, Alessia, Marcheselli, Raffaella, Sacchi, Stefano, Re, Alessandro, Pagani, Chiara, Tucci, Alessandra, Botto, Barbara, Vitolo, Umberto, Molinari, Anna Lia, Puccini, Benedetta, Pulsoni, Alessandro, Santoro, Armando, Tani, Monica, Nassi, Luca, Meli, Erika, Pavone, Vincenzo, Bonfichi, Maurizio, Evangelista, Andrea, Gioia, Daniela, Levis, Alessandro, and Zinzani Pier Luigi
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Oncology ,Adult ,Male ,medicine.medical_specialty ,hodgkin lymphoma ,Dacarbazine ,Absolute monocyte count ,Hodgkin lymphoma ,International Prognostic Score ,Neutrophil lymphocyte ratio ,PET ,Antineoplastic Combined Chemotherapy Protocols ,Autografts ,Bleomycin ,Disease-Free Survival ,Doxorubicin ,Female ,Humans ,Middle Aged ,Neoplasm Staging ,Positron-Emission Tomography ,Survival Rate ,Vinblastine ,Hodgkin Disease ,Stem Cell Transplantation ,Internal medicine ,medicine ,Autologous transplantation ,absolute monocyte count ,international prognostic score ,neutrophil lymphocyte ratio ,Survival rate ,Hematology ,business.industry ,Correction ,General Medicine ,Hodgkin's lymphoma ,medicine.disease ,Transplantation ,ABVD ,Original Article ,business ,medicine.drug - Abstract
The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.
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- 2020
37. Clinical characteristics of interim-PET negative patients with a positive end PET from the prospective HD08-01 FIL study
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Alessandro Pulsoni, Barbara Botto, Alessandro Re, Manuel Gotti, Michele Spina, Luigi Rigacci, Andrea Evangelista, Sofia Kovalchuk, Daniela Gioia, Lara Mannelli, Manjola Dona, Luca Nassi, Benedetta Puccini, Alessandro Broccoli, Caterina Stelitano, Flavia Salvi, Armando Santoro, Chiara Pagani, Pier Luigi Zinzani, Maurizio Bonfichi, Rigacci, Luigi, Puccini, Benedetta, Broccoli, Alessandro, Dona, Manjola, Gotti, Manuel, Evangelista, Andrea, Santoro, Armando, Bonfichi, Maurizio, Re, Alessandro, Spina, Michele, Botto, Barbara, Pulsoni, Alessandro, Pagani, Chiara, Stelitano, Caterina, Salvi, Flavia, Nassi, Luca, Mannelli, Lara, Kovalchuk, Sofia, Gioia, Daniela, and Zinzani, Pier Luigi
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Adult ,Male ,medicine.medical_specialty ,Salvage therapy ,Vinblastine ,Procarbazine ,Gastroenterology ,Disease-Free Survival ,advanced Hodgkin lymphoma ,interim-PET ,prognosis ,Bleomycin ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biopsy ,medicine ,Humans ,Prospective Studies ,Autografts ,Prospective cohort study ,Survival rate ,medicine.diagnostic_test ,business.industry ,Standard treatment ,Retrospective cohort study ,Hematology ,General Medicine ,Hodgkin Disease ,Dacarbazine ,Survival Rate ,Doxorubicin ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Prednisolone ,Female ,business ,Stem Cell Transplantation ,030215 immunology ,medicine.drug - Abstract
FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of patients with a positive e-PET as a secondary end point of the HD0801 study. A total of 519 patients with advanced-stage de novo Hodgkin lymphoma received initial treatment and underwent an i-PET. Patients with negative results continued the standard treatment. i-PET negative patients were then evaluated for response with an e-PET and those patients found to have a positive one were also then given a salvage therapy. Among 409 i-PET negative, 16 interrupted the therapy, 393 patients were evaluated with an e-PET, and 39 were positive. Sixteen out of 39 underwent a diagnostic biopsy and 15 were confirmed as HD. Seventeen out of 39 e-PET were reviewed according to the Deauville Score and, in sixteen, it was confirmed positive (10 DS 5, 6 DS 4). With the exception of high LDH value at diagnosis (p = 0.01; HR 95% CI 1.18-4.89), no clinical characteristics were significantly different in comparison with e-PET negative patients. Positive e-PET after a negative i-PET has a worse outcome when compared with i-PET positive patients salvaged with therapy intensification. It was not possible to identify clinical characteristics associated with a positive e-PET.
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- 2020
38. Metabolic behavior and prognostic value of early and end of treatment 18F-FDG PET/CT in adult Burkitt’s lymphoma: the role of Deauville and IHP criteria
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Raffaele Giubbini, Domenico Albano, Alessandro Re, Francesco Bertagna, Giovanni Bosio, and Chiara Pagani
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Adult ,Male ,Cancer Research ,Burkitt’s lymphoma ,Adolescent ,PET/CT ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Adult Burkitt's lymphoma ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Deauville criteria ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,PET-CT ,business.industry ,Disease Management ,International Harmonization Project ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Burkitt Lymphoma ,Predictive value ,Interim pet ,Lymphoma ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Fdg pet ct ,Energy Metabolism ,business ,Nuclear medicine ,Burkitt's lymphoma ,Biomarkers ,030215 immunology - Abstract
Burkitt's lymphoma is a lymphoma with unclear metabolic behavior at 18F-FDG-PET/CT and no validated criteria in treatment evaluation and prediction of outcome exist. Sixty-five patients were retrospectively included: all underwent baseline 18F-FDG-PET/CT, 56 interim PET/CT (iPET/CT) and 54 end of treatment PET/CT (eotPET/CT) after chemotherapy. Interim and eotPET/CT results were visually interpreted according to the criteria of the IHP and Deauville-five-point-scale. Results were correlated with PFS and OS to assess and to compare the predictive value of iPET and eotPET according to each criterion. All baseline PET/CT showed increased 18F-FDG uptake in nodal and extranodal lesions. The median PFS and OS were 44.6 and 48.2 months with 3-year and 5-year PFS of 76% and 62% and 3-year and 5-year OS of 71% and 57%, respectively. EotPET/CT results using DC and IHP significantly correlate with OS and PFS; while iPET/CT did not correlated with OS and PFS.
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- 2018
39. Do MYC Alterations Matter in HIV-Associated Large B Cell Lymphomas? the 'Euromyc' Study (a European retrospective study)
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Davide Dalu, Giuseppe Rossi, Luca Arcaini, Alessia Dalla Pria, Fabio Facchetti, Philipp Schommers, Chiara Pagani, Luisa Verga, Mariana Bastos-Oreiro, Chiara Rusconi, Emanuele Ravano, Michele Spina, Sara Steffanoni, Alessandro Re, Alessandra Tucci, Guido Gini, and Chiara Cattaneo
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Human immunodeficiency virus (HIV) ,Retrospective cohort study ,Cell Biology ,Hematology ,medicine.disease_cause ,Biochemistry ,medicine.anatomical_structure ,Internal medicine ,medicine ,business ,B cell - Abstract
Introduction: In the general HIV negative population, patients (pts) with diffuse large B cell lymphoma (DLBCL) or high grade B cell lymphoma (HGBCL) carrying MYC rearrangements and BCL2 and/or BCL-6 translocations [double hit (DHL) or triple hit lymphomas (THL)] have shown a dismal prognosis when treated with standard R-CHOP and are frequently candidates to intensive therapeutic regimens, without having a standard of care. Moreover, several authors have demonstrated a negative prognostic impact of isolated MYC rearrangements [single hit lymphomas (SHL)] and the best therapeutic approach for SHL are even less clear. In HIV-associated "non Burkitt" large B cell lymphomas (Ly), scanty data are available on the prevalence and the clinical and prognostic impact of MYC rearrangements, with or without BCL2 and BCL6 concomitant translocations. Due to the peculiar biology and pathogenesis of HIV-associated Ly, data from HIV negative population cannot be simply translated to the HIV positive pts. Aim: To evaluate the impact of MYC rearrangements or translocations (isolated or with BCL2 and/or BCL6 translocations) on clinical features and outcome of HIV-associated large B cell Ly. Methods: Retrospective analysis of clinical characteristics, treatment received and outcome of all HIV-associated large B cell Ly [including DLBCL, B cell Ly unclassifiable, with features intermediate between DLBCL and Burkitt (BCLU), and HGBL] with MYC rearrangements or translocations, evaluated by FISH analysis, in 11 European centers, and comparison with pts who do not have the MYC alterations. Results: One hundred-sixty-one pts were enrolled, 49 (30%) had MYC translocation or other MYC rearrangements (MYC+ pts), and 112 (70%) were negative for MYC mutation (7 pts had MYC increased copy number) (MYC- pts). Table 1 shows the clinical characteristics of the two groups, and the treatment received. MYC+ pts had higher involvement of central nervous system at presentation (17% vs 3%, p 0,023), higher Ki67% (median 91% vs 85%, p 0,005), histology other than DLBCL (32% vs 9%, p 0,0001), concomitant translocation of BCL2 (14% vs 3%, p 0,022), germinal center B phenotype (according to Hans algorithm) (85% vs 49%, p 0,0001). No differences in CD4 count or HIV viral load at Ly diagnosis were found, while a previous diagnosis of AIDS was more frequent in the MYC- group (27% vs 10%, p 0,023). MYC+ pts received more frequently intensive treatment (iCT) (41% vs 12%, p 0,0001) and less frequently the standard CHOP regimen (41% vs 74%, p 0,001). Ten pts (9%) had a DHL/THL and had similar clinical characteristics compared to SHL. With a median follow-up of 62 months, there were no significant differences in overall survival (OS) and progression-free survival (PFS) between MYC+ and MYC- pts (5 years-OS and PFS were respectively 55% and 47% in MYC+ and 59% and 53% in MYC- pts). In univariate analysis for the whole population, IPI≥3, ECOG≥ 2 and increased LDH were related to a worse OS and PFS while BCL2 translocation correlated with shorter PFS alone. In multivariate analysis ECOG and IPI mainteined their negative prognostic impact on OS and PFS. In the MYC+ group, 41% pts received R-CHOP or CHOP-like treatment (group 1), 16% infusional therapy (group 2), 41% iCT (group 3), 2% palliative therapy (PT) (group 4); 5-years OS and PFS were 47% and 32% for group 1, 47% and 37% for group 2, 67% and 68% for group 3 and both 0% for group 4. Median OS and PFS were respectively 18 and 2 months for group 1, 29 and 7 months for group 2, both not reached for group 3, both 2 months for group 4. A significant difference between group 3 and group 1 both in therm of OS (p 0,054) and PFS (p 0,005) was observed (Figure 1). Pts with DHL/THL received R-CHOP (40%), infusional schedule (30%), iCT (20%) and PT (10%). No significant difference in term of PFS and OS were observed for each treatment group with DHL/THL respect to those with SHL. In DHL/THL, 5 years OS and PFS were 50% and 30%, respectively; in SHL 56% and 51%, respectively. Of note, no pts treated with iCT died from toxicity in the MYC+ group. Conclusion: In this retrospective analysis, MYC+ pts had not different clinical characteristics compared to MYC- pts other than higher proliferative index and and more CNS involvement at diagnosis. MYC+ pts were frequently treated with iCT, this aggressive approach seemed feasible and could allow to obtain better outcome compared to standard R-CHOP treatment but further prospective studies are needed. Figure 1 Figure 1. Disclosures Bastos-Oreiro: F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Arcaini: Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Gilead Sciences: Research Funding; Celgene: Speakers Bureau. Rossi: Novartis: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.
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- 2021
40. A Simplified Geriatric Assessment (sGA) Can Identify Older Patients with Relapse/Refractory (R/R) Aggressive Lymphoma Suitable for Autologous Stem Cell Transplantation (ASCT): Final Results of Recanz Multicentre Prospective Phase 2 Study By the Fondazione Italiana Linfomi (FIL)
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Francesca Re, Manuela Zanni, Alessandra Tucci, Giuseppe Rossi, Luigi Marcheselli, Mariagrazia Michieli, Giulia Campostrini, Vittorio Ruggero Zilioli, Chiara Pagani, M. Christina Cox, Federica Cavallo, Monica Tani, Alessandro Re, Sabrina Pelliccia, Eliana Valentina Liardo, Donato Mannina, Gerardo Musuraca, Daniele Grimaldi, Daniele Vallisa, and Francesco Merli
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Oncology ,medicine.medical_specialty ,business.industry ,education ,Immunology ,Phases of clinical research ,Aggressive lymphoma ,Geriatric assessment ,Cell Biology ,Hematology ,Biochemistry ,Autologous stem-cell transplantation ,Refractory ,Older patients ,Internal medicine ,medicine ,business ,health care economics and organizations - Abstract
Introduction: We recently demonstrated in a large multicentre study that sGA can identify fit older patients with aggressive lymphoma able to tolerate first-line intensive treatment with curative intent and to obtain similar results than younger people (Merli at al JCO 2021). Regardless of age, about 40% of patients with aggressive lymphoma are either refractory or will eventually relapse after treatment with curative intent. Salvage platinum-based regimens followed by ASCT in responsive disease is a standard of care to obtain longer second remission. However, in many case series, patients over 65 years are excluded from the transplant approach because of potential severe toxicities of high-dose therapy in older patients. This study was designed to evaluate the feasibility and activity of high-dose treatment followed by ASCT in older FIT patients with R/R aggressive lymphoma selected with a sGA. Methods: Patients with R/R aggressive lymphoma after one line of treatment, aged between 65 and 75, and FIT to sGA were eligible for the study. Salvage treatment could be chosen between R-DHAP, R-ICE or other platinum or gemcitabine-containing regimens and stem cells were mobilized after 1 or 2 cycles. Patients achieving at least partial response after 3 courses and who remained FIT to sGA evaluation were eligible for ASCT and were conditioned with either BEAM or FEAM. Results: From May 2014 to August 2019, seventy-five patients from 16 FIL centres were enrolled and 70 were eligible for the study. Sixty-six of them had a diffuse large B-cell lymphoma, one had follicular 3b, 2 mantle cell and 1 Burkitt histology. Salvage treatment was R-DHAP in 48 patients, R-ICE in seven and gemcitabine or oxalyplatinum containing regimens in the remaining ones. Overall response rate after three courses was 44% (21 complete and 10 partial remission). Among the 39 unresponsive patients, 29 had progressive and 4 stable disease, 2 patients died of septic shock and heart failure during salvage and 4 patients withdrew their consent to ASCT. Four patients relapsed soon after response achievement before undergoing the transplant. ASCT was performed in 27 patients with a median of 5.6 x 10 6 CD34/Kg reinfused. No differences emerged in demographic and clinical characteristics between patients reaching the ASCT timepoint or not (Tab 1a). By intention to treat analysis, 2-y overall survival (OS) and PFS of the entire intention-to-treat population were 65% (95%CI: 50-76%) and 34% (95%CI: 22-46%) respectively, without differences according to age (Tab 1b). After a median of 27 months, 2-y OS was 79% (95CI: 51-86%) and EFS 56% (95CI: 32-75%). Twenty-four patients obtained a complete remission (CR) and 20 of them are in continuous CR after more than 12 months. Three patients progressed 1-8 months after ASCT and died. Most common non-hematologic grade 3-4 adverse events were gastrointestinal (10%) and infectious (8%). Conclusion: This study shows that sGA can identify older patients with R/R aggressive lymphoma who are able to tolerate and can benefit from high-dose therapy and ASCT. The poor response to second-line immunochemotherapy remains the major drawback of this approach since less than 50% of patients could actually receive ASCT. Nevertheless the 2-y survival of 65% in the intention to treat population is remarkable and sets the stage for the evaluation of new approaches such as CAR-T or bispecific antibodies also in older patients. A next step should be to explore the usefulness of sGA in the selection of candidates to these innovative treatments. Figure 1 Figure 1. Disclosures Tucci: Takeda: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees. Musuraca: janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavallo: ROCHE: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Gilead: Speakers Bureau. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau; Takeda: Other: travel expenses, accommodation. Merli: EUSA Pharma: Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses. Marcheselli: sandoz: Membership on an entity's Board of Directors or advisory committees. Rossi: Abbvie: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees.
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- 2021
41. Adverse Prognostic Role of IDH2 Mutations at Diagnosis and during Follow-up in Patients with Acute Myeloid Leukemia and Normal Karyotype
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Margherita Oberti, Margherita Sciumé, Elisa Cerqui, Diego Bertoli, Alessandra Tucci, Chiara Cattaneo, Rossella Leopaldo, Chiara Pagani, Erika Borlenghi, Cecilia Carbone, Giuseppe Rossi, Nicola Bianchetti, and Silvana Archetti
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Myeloid leukemia ,Karyotype ,Cell Biology ,Hematology ,Biochemistry ,IDH2 ,Internal medicine ,medicine ,In patient ,business - Abstract
Introduction: Acute Myeloid Leukemia (AML) is a heterogeneous disorder characterized by a wide range of cytogenetic and molecular aberrations, that affect prognosis and guide treatment decisions. However there is a still large group of patients (pts) considered at intermediate risk whose outcome needs to be better defined. Next-generation sequencing (NGS) can simultaneously detect various mutations, leading to better define its prognostic profile. The role of some mutations, including isocitrate dehydrogenase (IDH) mutations (IDHm), is still controversial. Aim: We evaluated by NGS monitoring at different time points the prognostic role of IDH1/2m in AML pts with normal karyotype, both in the subgroup with mutations of NPM1 (NPM1m) or FLT3 (FLT3m) and in the subgroup without detectable mutations (wt-AML). Methods: Using Sophia Myeloid Solution kit (SOPHiA Genetics), we performed targeted NGS, covering 30 gene regions, in 104 bone marrow samples collected at diagnosis (53), after first consolidation (30) and at relapse (21), in 53 pts (M/F: 24/29; median age: 56 y, range 22-74), treated according to NILG-AML00 protocol (NCT00400673). Standard PCR to detect NPM1m and FLT3m was performed and we identified 20 NPM1m, 3 NPM1+FLT3-ITDm, 4 FLT3-ITDm and 26 wt-AML. Results: At diagnosis, among 219 pathogenic mutations detected, IDHm represented 10.5% of them (median VAF: 39.1%; range 6.2-49.6%). IDHm was observed in 23/53 pts (43.4%) (IDH1m in 11 and IDH2m in 12). In these pts , more frequently commutated genes were DNMT3A (28%), NPM1 (13%), FLT3-ITD/TKD (14%), ASXL1 (6%), SRSF2 and NRAS (9% each). Complete remission (CR) was achieved in 49/53 (92.5%) pts without difference in response rate according to IDH status (86% in IDHm vs 94% in IDH wild-type, wt). Relapse occurred in 28/49 (57%) pts after a median of 11 months (mo), range 2-61. The frequency of relapse was not significantly different across all types of mutations identified, except for IDH2m which was associated with a higher risk of relapse (10/11 in IDH2m vs 18/38 in IDH2wt; p: 0.014), without differences between R172K and R140Q. On the contrary, IDH1m, present in 18% of relapsed pts, did not impact on relapse (5/10 vs 23/39, p: 0.7). Particularly, in the wt-AML group, the IDH2m was prevalent in pts developing relapse (6/11, 54.5%) and all pts with IDH2m relapsed, with median of 13 mo, range 6-24 (6/6 in IDH2m vs 5/17 in IDH2wt, p:0.0046). Among the co-occurrence mutations, the IDH2/DNMT3A was associated with higher relapse risk (9/9 vs 19/40; p: 0.0063). DNMT3A associated with other mutations did not impact on relapse risk. At a median follow-up of 23 mo, median relapse free survival (RFS) and overall survival (OS) of whole population were 24 and 53 mo, respectively. The IDH2m impacted on OS: 23.5 mo in IDH2m vs 72 in IDH2wt pts (p:0.0093) (Fig 1a), but not in RFS (13 vs 29 mo in IDH2m and IDH2wt, respectively (p:0.1). Considering the subgroups of wt-AML, the RFS (Fig. 1b) and OS were 13 and 23.5 mo in IDH2m vs undefined in IDH2-wt (p:0.0014 and p:0.1), respectively. In pts with NPM1 or FLT3m, RFS and OS were 9 and 53 mo in IDH2m vs 29 and 73 mo in IDH2-wt (p:0.2 and p:0.15), respectively. We did not find the other genomic pattern predicting relapse in this group. After consolidation, NGS monitoring was performed in 30 pts in CR. Of the 13 IDH AML pts evaluated, no mutations was observed in 4 (28.5%); the persistence of IDHm was not associated with a significantly higher relapse (p:0.5). Among other mutations present at diagnosis, NGS clearance after consolidation occurred in pts with NRAS, KRAS, PTPN11 and FLT3-ITD/TKD. Conversely, it was limited for the following mutations: TET2 (8/11), DNMT3A (7/13), SRSF2 (6/6), IDH2 (4/5), ASXL1 (2/2), IDH1 (2/4) and NPM1 (1/12). Overall, the persistence of any type of gene mutations after consolidation was predictive of relapse (2/9 vs 6/7, p:0.04), only in wt-AML subgroup. At relapse, of the 11 IDHm pts analyzed, 7/7 IDH2m and 3/4 IDH1m showed the reappearance of mutations. Conclusion: In this retrospective monocentric study, the presence at diagnosis of IDH2m correlated with relapse risk and with survival, suggesting that additional treatment with targeted agents and or consolidation with allogeneic transplant should be considered. In addition, in AML without NPM1m or FLT3m, the persistence of genes mutation detected by NGS monitoring after consolidation had a significant prognostic value to predict subsequent relapse. Figure 1 Figure 1. Disclosures Borlenghi: Amgen, Janssen: Consultancy. Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Tucci: Gentili: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.
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- 2021
42. Longitudinal Serological Response to Sars-COV-2 in Patients Affected By Hematologic Diseases
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Chiara Cattaneo, Valeria Cancelli, Chiara Pagani, Alessandra Tucci, Giuseppe Rossi, Luisa Imberti, Alessandra Sottini, Kerry Dobbs, Elana Shaw, Luigi D. Notarangelo, Jeffrey Cohen, and Peter Burbelo
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Convalescence ,media_common.quotation_subject ,Immunology ,Population ,Lymphoproliferative disorders ,203.Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Lymphoma ,Hematologic disease ,Chemoimmunotherapy ,Internal medicine ,medicine ,Rituximab ,Seroconversion ,education ,business ,media_common ,medicine.drug - Abstract
Introduction. Covid-19 patients (pts) with hematologic malignancies have a severe prognosis with mortality rates around 40%, particularly when on active treatment (Cattaneo et al, Cancer, in press). However, the long-term prognosis and persistence of specific immune responses among those who survive acute infection are unclear. Aim: Pts with hematological diseases were followed longitudinally after the acute phase of COVID-19 according to protocol NP4156 approved by the local EC. Clinical outcome and specific antibody responses to SARS-CoV-2 were monitored during convalescence, and correlated to the diagnosis and treatment of the underlying hematological disease. Pts and Methods. Pts affected by multiple myeloma (MM), follicular (FL) and diffuse large B-cell (DLC) lymphoma (NHL), chronic lymphoproliferative disorders (CLD), myelodysplastic/chronic myeloproliferative syndromes (MDS/MPN) and surviving the acute phase of virologic-proven COVID-19 were eligible. Immune response parameters were evaluated at +1, +3, +6, +9 and +12 months after nasal swab negativization. Antibodies (Ab) to different conformations of COVID-19 virus proteins, nucleocapsid (N) and spike (S), were measured using a highly sensitive luciferase-immunoprecipitation system (LIPS) assay. Results. Of 51 eligible pts, 41 were tested for SARS-CoV-2 Ab at first timepoint (+1m) (6 pts too early, 2 refusal, 2 lost to follow-up). For 9 of them, Ab levels at +3m were also available. Ab levels of 14 controls without hematologic disorders (Ctrls) also surviving COVID-19 were evaluable at +1m and in 9 of them at +3 months as well. Diagnoses included FL (9) and DLC (6) NHL, CLD (7), MM (10), MDS/MPS (9). The status of hematological disease at the time of COVID-19 diagnosis was as follows: diagnosis (n=4; 10%), complete or partial remission (n=16; 39%), relapse/refractory (n=6; 15%; stable (n=15; 36%). Twenty-one pts (51%) were on active treatment, including 6 on chemoimmunotherapy; 7 pts had received chemoimmunotherapy previously. Median time from SARS-CoV-2 detection to swab negativity was 30d (range 8-63), and was not influenced by sex, age, hematologic diagnosis, disease status, nor treatment received. Two pts, both affected by DLC secondary to FL, remained swab-positive at day 119+ and 123+. At +1m, both N- and S- seropositivity rate was slightly lower in pts [N+ in 30/41 (73%); S+ in 27/41 (66%)] vs 13/14 for both N+ and S+ in Ctrls (93%) (P=0.16 and 0.08, respectively). Discrepancies between N and S seropositivity were observed in 7 (17%) pts, all with lymphoid disorders. Ab levels were similar in hematologic pts and in Ctrls (N+ 894,707 vs 870,541 LU and S+ 907,591 LU vs 724,120 LU, respectively, P=NS) (Fig.1a). Both seroconversion rates and Ab levels were not influenced by age, sex, status of hematologic disease, ongoing treatment, time to swab negativity, severity of pneumonia and steroid treatment during acute COVID-19. However, a diagnosis of NHL negatively impacted on seroconversion for both N and S. In 15 pts with NHL compared to 26 pts with other hematologic cancers, the N-seropositivity rate was 47% vs 92%, and the S-seropositivity rate was 40% vs 85%y (P=0.002 and 0.0053, respectively). N and S Ab levels were also lower than in other hematologic diseases (515,281 LU vs 1105409 LU, P=.002 and 474,309 LU vs 1,148,303 LU, P=.005 respectively) (Fig.1b). Rituximab (RTX) had been used in 13 of 15 NHL (87%), and treatment was ongoing in 6/13. While N-seroconversion and Ab levels were not influenced, no pts on ongoing RTX had S-seroconversion vs 5/7 pts with past RTX use (P=0.021) and mean antibody levels were 17622 LU vs 668548 LU, respectively (P=0.008). At +3m, no significant variations of both anti-N and anti-S antibody levels had occurred compared to timepoint +1m. Seroconversion status was maintained by 9/9 Ctrls and by 8/8 pts; the only pt with Ab levels below the cut-off at +1m did not show seroconversion at+3m. Conclusions: Overall, hematologic pts surviving COVID-19 have N- and S- antibodies levels and seroconversion rates similar to controls without hematologic disorders, although time to swab negativity seems more similar to critically ill pts than in the general population. A diagnosis of NHL negatively impacts on seroconversion and Ab levels, and ongoing RTX seems to have a negative role specifically on anti-S Ab production. Ab response persists at 3 months; the study is ongoing and further data will be available at time of meeting. Disclosures Tucci: Amgen: Consultancy. Rossi:Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Amgen: Honoraria; Novartis: Other: Advisory board; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria. Imberti:Biogen: Honoraria; Genzyme-Sanofi: Honoraria; Meck-Serono: Honoraria; Novartis: Honoraria; Biogen: Other: Advisory board; FISM (Fondazione Italiana Sclerosi Multipla): Research Funding; Regione Lombardia: Research Funding. Notarangelo:NIAID, NIH: Research Funding. Cohen:NIAID, NIH: Research Funding.
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- 2021
43. Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels
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Samantha Ferrari, Giuseppe Rossi, Luisa Lorenzi, Chiara Pagani, Mariella D'Adda, Alessandra Tucci, Nicola Bianchetti, Doriana Gramegna, Annamaria Pelizzari, Gabriella Vona, and Chiara Bottelli
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medicine.medical_specialty ,Univariate analysis ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Immunology ,Cell Biology ,Hematology ,Hematocrit ,medicine.disease ,Single Center ,Biochemistry ,Thrombosis ,Polycythemia vera ,Internal medicine ,medicine ,Risk factor ,Prospective cohort study ,business - Abstract
Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P= In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.
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- 2020
44. Rituximab with Dose-Adjusted EPOCH (R-DA-EPOCH) with or without Autologous Stem Cell Transplantation (ASCT) As First Line Treatment in Patients with Aggressive B-Cell Lymphoma with MYC and BCL-2 and/or BCL-6 Gene Rearrangements or Increase Copy Number
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Carmelo Carlo-Stella, Rosa Daffini, Luisa Lorenzi, Fabrizio Marino, Alessandra Tucci, Paolo Corradini, Alessandro Re, Fabio Facchetti, Giulia Soverini, Giuseppe Rossi, Chiara Pagani, Piera Balzarini, Anna Guidetti, Ivana Casaroli, Giulia Campostrini, Anna Dodero, and Monica Balzarotti
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business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,First line treatment ,Autologous stem-cell transplantation ,Cancer research ,Medicine ,Rituximab ,In patient ,EPOCH (chemotherapy) ,business ,B-cell lymphoma ,Gene ,medicine.drug - Abstract
Introduction: We have previously reported short-term efficacy of six courses of R-DA-EPOCH in patients with aggressive B cell lymphomas carrying concomitant MYC and BCL-2 and/or BCL-6 rearrangement (DHL/THL) or gene increase copy number (ICN) (Tucci et al. Blood S1: 4154, 2017). Further experience with the same program has been described in the meantime in patients with aggressive lymphoma and c-MYC rearrangement, either as single hit or DHL/THL (Dunleavy et al. Lancet Haematol, 2018). We report here long-term results in a larger unselected series of DHL/THL with the aim to confirm our preliminary results and to define the role of consolidation with autologous stem cell transplantation (ASCT) after R-DA-EPOCH remission induction. Methods: The study includes patients consecutively seen in four Italian centres. From January 2014, fit patients aged less than 80 years, with diffuse large B cell lymphoma (DLBCL), lymphoma with intermediate features between DLBCL and Burkitt (BCLU) or high grade lymphoma (HGBCL) histology, diagnosed as DHL or THL by fluorescent in situ hybridization (FISH), were treated with R-DA-EPOCH and central nervous system prophylaxis. Patients with MYC -ICN (three or more extra signals in more than 30% of nuclei, Schieppati et al. Haematologica, 2019) plus BCL-2 and/or BCL-6 gene rearrangement or ICN were also included. Pre-treatment with one cycle of R-CHOP was allowed in patients in need of urgent treatment, pending the results of FISH analysis. Consolidation with ASCT was planned in three of the four centres for stage II-IV patients aged less than 71 who reached at least a partial remission (PR) after six R-DA-EPOCH courses. Immunohistochemistry (IHC) was used to define cell of origin (COO) according to Hans' algorithm, double expressor cases (MYC and BCL-2 protein >40% and 50% respectively) and Ki67 expression. Results: Sixty-three patients were treated (51 DLBCL, 5 BCLU, 7 HGBCL, including 16 with histologic transformation from an indolent lymphoma). Their median age was 63 years (range 23-79) and 43 (68%) were males. Fifty-four (86%) had Ann-Arbor stage III/IV, 18 (28%) B symptoms and 41 (65%) high-intermediate/high risk score according to International Prognostic Index (IPI), with extranodal disease in 79% of patients, mainly in bone and gastrointestinal tract. According to FISH analysis, 34 cases were DHL, 10 THL and 19 c-MYC-ICN. According to IHC, 81% were of germinal center origin, 73% were double expressors and median Ki-67 was 91% (range 35-100%). Patients received a median of six courses of R-DA-EPOCH (range 1-6). Twelve patients were pre-treated with one R-CHOP course and 24 patients (17 in complete remission, 6 in PR and 1 with disease progression) received transplant consolidation (allogeneic SCT in one PR patient), according to the policy of the centre and eligibility criteria. In the entire cohort, the overall response rate was 81%, including 68% complete responses (CR) and 3y-PFS and OS were 67% and 69% respectively. Two patients died of infectious complications during chemotherapy. Of the 10 chemo-refractory patients, all have died of lymphoma. Median length of follow-up was 32 months. At univariate analysis, IPI > 3 and THL were significantly associated with a worse outcome while cMYC-ICN and ASCT with a better OS. At multivariate analysis, only ASCT remained significantly associated with better survival (HR 0.146, IC 95% 0.032-0.667, p 0.013). Focusing on patients who achieved CR with R-DA-EPOCH, all 17 patients who underwent transplantation (100%) are alive (after a median of 27 months from transplant), versus 19 out of 24 patients (79%) who did not. Only one patient relapsed after ASCT and is alive after receiving CAR-T cells. 3y-OS and PFS of patients in CR after induction therapy who received or not ASCT consolidation were 100% vs 76% and 94% vs 72% respectively (Fig.1). Clinical characteristics of the two subgroups were similar except for median age that was lower in the former one (59 vs 69 years). Conclusions: These results confirm the favourable outcome of patients with MYC and BCL-2 and/or BCL-6 rearrangements or gene ICN with R-DA-EPOCH therapy. The role of consolidative ASCT and its usefulness seems encouraging, but remains to be proven by prospective randomized studies. The poor outcome of chemo-refractory patients represents an unmet need and greater expansion of CAR-T cell programs could improve these results in the near future. Disclosures Tucci: Amgen: Consultancy. Carlo-Stella:Boehringer Ingelheim and Sanofi: Consultancy; Servier, Novartis, Genenta Science srl, ADC Therapeutics, F. Hoffmann-La Roche, Karyopharm, Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca: Honoraria; ADC Therapeutics and Rhizen Pharmaceuticals: Research Funding. Corradini:Takeda: Consultancy, Honoraria, Other; BMS: Other; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; KiowaKirin: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodations paid by for; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Amgen: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Daiichi Sankyo: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Incyte: Consultancy; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations paid by for. Rossi:Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria.
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- 2020
45. An increase in
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Francesca, Schieppati, Piera, Balzarini, Simona, Fisogni, Alessandro, Re, Chiara, Pagani, Nicola, Bianchetti, Lorenzo, Micheli, Angela, Passi, Samantha, Ferrari, Adriana, Maifredi, Chiara, Bottelli, Rossella, Leopaldo, Vilma, Pellegrini, Fabio, Facchetti, Giuseppe, Rossi, and Alessandra, Tucci
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Proto-Oncogene Proteins c-myc ,B-Lymphocytes ,DNA Copy Number Variations ,Proto-Oncogene Proteins c-bcl-2 ,Non-Hodgkin Lymphoma ,Proto-Oncogene Proteins c-bcl-6 ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Articles ,Prognosis ,In Situ Hybridization, Fluorescence ,Translocation, Genetic - Abstract
MYC translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of MYC have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of MYC increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for MYC, BCL2, and BCL6 rearrangements. We enumerated the number of MYC copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of MYC translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with MYC copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of MYC extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of MYC had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with MYC translocation. The survival of patients with >4 copies, translocation or amplification of MYC seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence in situ hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of MYC.
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- 2019
46. Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in Burkitt lymphoma
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Alessandro Re, Giovanni Bosio, Alessandra Tucci, Francesco Bertagna, Raffaele Giubbini, Chiara Pagani, and Domenico Albano
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Adult ,Male ,MTV ,TLG ,Adolescent ,Aggressive lymphoma ,Standardized uptake value ,030218 nuclear medicine & medical imaging ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,Positron Emission Tomography Computed Tomography ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Survival analysis ,Aged ,Aged, 80 and over ,Fluorodeoxyglucose ,Body surface area ,business.industry ,18F-FDG PET/CT ,Burkitt lymphoma ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Lymphoma ,030220 oncology & carcinogenesis ,Lean body mass ,Female ,Radiopharmaceuticals ,medicine.symptom ,Nuclear medicine ,business ,Glycolysis ,medicine.drug - Abstract
Burkitt’s lymphoma (BL) is an aggressive lymphoma subtype with high 18F-FDG avidity at 18F-FDG-PET/CT, but no validated criteria for PET/CT in treatment evaluation or prediction of outcome in BL are available. The aim of our study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in BL. We retrospectively enrolled 65 patients who underwent baseline 18F-FDG-PET/CT, interim and end of treatment PET/CT. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), the maximum standardized uptake value lean body mass (SUVlbm), the maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan–Meier method. At a median follow-up of 40 months, the median PFS and OS were 34 and 39 months. MTV and TLG were significantly higher in patients with partial response compared to complete response group at end of treatment, while no significant differences were found at interim. Other metabolic PET/CT parameters were not related to treatment response. MTV and TLG were demonstrated to be independent prognostic factors for both PFS and OS; instead SUVbw, SUVlbm, SUVbsa, L-L SUV R and L-BP SUV R were not related to outcome survival. Metabolic tumour features (MTV and TLG) were significantly correlated with response to treatment and long-term outcome.
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- 2019
47. Post Induction and Post Consolidation Measurable/Minimal Residual Disease Predict Relapse in NPM-1 Positive AML. Outcome of Treatment Relapse. a Single Center Experience
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Chiara Cattaneo, Margherita Sciumé, Rosa Daffini, Angela Passi, Cinzia Lamorgese, Diego Bertoli, Francesca Schieppati, Silvana Archetti, Giuseppe Rossi, Chiara Pagani, Erika Borlenghi, Mirella Marini, Doriana Gramegna, Nicola Polverelli, and Michele Malagola
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medicine.medical_specialty ,NPM1 ,business.industry ,medicine.medical_treatment ,Immunology ,Disease progression ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Impedance threshold device ,Single Center ,Biochemistry ,Minimal residual disease ,Chemotherapy regimen ,Internal medicine ,medicine ,business ,Etoposide ,medicine.drug - Abstract
Although the ELN MRD Working Party (Schuurhuis, 2018) recommends that Acute Myeloid Leukemia (AML) patients (pts) with mutated NPM1 (NPM1+) should have molecular assessment of measurable/minimal residual disease (MRD), the most clinically significant timepoints (TPs), the thresholds, the best source of samples, bone marrow (BM) or peripheral blood (PB) and especially the management of molecular relapse, remain controversial. We evaluated the prognostic significance of NPM1 molecular monitoring, its impact on disease recurrence and the outcome of salvage treatment. From Jul 2010 to dec 2018, 83 consecutive NPM1+ AML pts (M/F: 44/39; median age 59 y, 27-74) eligible for intensive chemotherapy (i-T) were treated, according to the NILG-AML00 protocol (ClinicalTrial.gov: NCT00400673): ICE (idarubicine-ARAC-etoposide) as induction, followed by IC consolidation and 3 further consolidation cycles of high-dose ARAC. Allogeneic stem cell transplant (HSCT) was considered at relapse. Quantitative RT-PCR was performed to detect NPM1 mutation (Gorello, 2006) on BM and PB samples at diagnosis (TP0) and at given TPs: at complete remission (CR) (TP1), post-IC (TP2), post-1st ARAC consolidation (TP3) and at the end of treatment (TP4). Serial MRD monitoring during follow-up was made on PB every 3 months (mo) for 5 years (y) or until relapse. Molecular relapse (mR) was defined as the NPM1 level increase at least 1 log in 2 consecutive samples, in absence of hematological relapse (hR). At baseline, karyotype (K) was abnormal in 8 pts (9.6%); 25 (30%) were FLT3-ITD mutated with a median Allelic Ratio (AR) of 0.35 (range: 0.2 to 2.18) (Pratcorona, 2013). During treatment, 608 samples were studied (383 BM and 225 PB), for a median of 8 per patient (range: 3 to 10). At TP1, a higher level of NPM1 unfavorably impacted on relapse (p 0.02) and a cut-off >200 *10^4/ABL was significantly associated with a higher relapse risk (RR) (68.7%) and lower RFS (p 0.006). Moreover, MRD positivity (value >0*10^4 NPM1/ABL) at TP2 on PB was associated to a higher RR (38.8%; p 0. 041) and a level >0.5*10^4/ABL allowed to predict relapse in 75% of pts, also impacting on RFS (p 0.0001) (Figure 1).Molecular NPM1 relapse/progression occurred in 10 pts early during treatment, after a median of 3.5 mo (1.4-6) from diagnosis and in 8 of them simultaneously with hR. In 16 pts mR occurred after a median CR duration of 18.5 mo (10.5-61.5) (late relapse). Hence a mR was more frequent in late than in early relapse (87.5% vs 20%; p 0.001). Median survival was 8.3 mo in early relapsing pts and was not reached in late relapsing pts (p. 0.0002). Age, NPM1 level at TP0, FLT3-ITD mutation, ITD-AR or abnormal K did not impact on type of relapse (mR or hR), but FLT3-ITD was more frequent in early than late relapse (60% vs 18.7%; p 0.04). After a median follow-up of 42 mo (4-108), 5-y relapse-free survival (RFS) and overall survival were 64.2% (+/-6.5% SE) and 71.1% (+/-6.1% SE), respectively. Overall, considering both mR and hR, 26 pts (31.3%) relapsed after a median of 13.5 mo after CR; 24/26 pts received a salvage treatment and 14 (53.8%) (median age 49y, 27-64) could proceed to HSCT after a median of 2.9 mo (5 too old, 7 early progression). Salvage treatment before HSCT was i-T in 7/14 and non-i-T in 7/14 pts (2 ATRA and 5 D-actinomycin, Falini 2015) for a median of 3 cycles (range 2-4). Disease status at HSCT was: mCR in 3 pts, CR with detectable MRD (median NPM1: 125*10^4/ABL, range 17.8-3849) in 9, refractory in 2 pts. Nine/14 HSCT pts (64.2%) are alive and in remission at a median of 29.6 mo (13-49) from HSCT, 2 pts died of sepsis in c-GVDH at 6.2 and 37.5 mo after HSCT, 1 died of VOD and 2 of disease progression. At 3 months after HSCT all MRD positive pts were NPM1 negative. mR occurred in 3 pts at 8, 12 and 15 mo after HSCT and was successfully treated with early pre-emptive donor lymphocyte infusions. With the limits of small numbers, age, type (mR or hR) or timing of relapse (early or late), disease status at HSCT, donor source and conditioning intensity didn't influence survival. Our study shows that PCR monitoring during treatment can identify pts at higher RR according to the transcript levels in BM and PB samples. In NPM1+ AML, molecular monitoring in PB during follow-up is of crucial importance in detecting late molecular relapse allowing to use less toxic molecular-oriented treatments as a bridge to HSCT. Further studies on larger cohorts hopefully will help to confirm its usefulness to guide the treatment approach. Disclosures Rossi: Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: D-actinomicin
- Published
- 2019
48. Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in mantle cell lymphoma
- Author
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Nicola Bianchetti, Alessandra Tucci, Giovanni Bosio, Chiara Pagani, Alessandro Re, Francesco Bertagna, Domenico Albano, and Raffaele Giubbini
- Subjects
Adult ,Male ,MTV ,TLG ,Standardized uptake value ,Aggressive lymphoma ,Lymphoma, Mantle-Cell ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,18F-FDG PET/CT ,Mantle cell lymphoma ,Prognosis ,Survival analysis ,Aged ,Retrospective Studies ,Body surface area ,Aged, 80 and over ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Response to treatment ,Treatment Outcome ,ROC Curve ,030220 oncology & carcinogenesis ,Lean body mass ,Fdg pet ct ,Female ,Nuclear medicine ,business - Abstract
Mantle cell lymphoma (MCL) is an aggressive lymphoma sub-type with poor prognosis and high 18F-FDG avidity at PET/CT; nowadays, no validated criteria for PET/CT in treatment response evaluation and prediction of outcome are present. The aim of study was to investigate whether the metabolic PET/CT features may predict treatment evaluation and prognosis in MCL. We retrospectively enrolled 87 patients who underwent baseline 18F-FDG PET/CT and 85 end-of-treatment (eot) PET/CT. The baseline PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-liver SUVmax ratio (L-L SUV R), lesion-to-blood pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). EotPET/CT was visually interpreted according to the criteria of the Deauville 5-point scale (DC). Survival curves were plotted according to the Kaplan–Meier method. At a median follow-up of 40 months, relapse/progression occurred in 47 and death in 23 patients. Median PFS and OS were 30 and 41 months. Baseline MTV and TLG were significantly higher in patients with progressive metabolic response compared to complete/partial response group. EotPET/CT results using DC significantly correlated with PFS, not with OS. MTV and TLG were demonstrated to be independent prognostic factors for PFS; instead the other metabolic parameters were not related to outcome survival. Considering OS, no variable was significantly associated. EotPET/CT results (using DC), MTV and TLG were significantly correlated with response to treatment and PFS.
- Published
- 2019
49. Postremission sequential monitoring of minimal residual disease by <scp>WT</scp> 1 Q‐ <scp>PCR</scp> and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients
- Author
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Valeria Cancelli, Giuseppina Ruggeri, Cinzia Lamorgese, Cristina Skert, Viviana Giustini, Enrico Morello, Giuseppe Rossi, Michele Malagola, Marco Chiarini, Federica Cattina, Rossella Ribolla, Simona Bernardi, Chiara Cattaneo, Chiara Pagani, Erika Borlenghi, Domenico Russo, Luisa Imberti, Elisa Cerqui, Angela Passi, and Luigi Caimi
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Myeloid leukemia ,Retrospective cohort study ,Bioinformatics ,Minimal residual disease ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,medicine.anatomical_structure ,Median follow-up ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Bone marrow ,business ,Survival analysis ,030215 immunology - Abstract
Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P
- Published
- 2015
50. Ultrasound detection of aortoenteric fistula in a patient with sepsis
- Author
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Chiara Pagani, Tiziano Perrone, and Elisa Eleonora Mossolani
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Male ,medicine.medical_specialty ,Point-of-Care Systems ,Fistula ,Aortic Diseases ,Aortoenteric fistula ,Case Report ,030204 cardiovascular system & hematology ,Diagnosis, Differential ,Lesion ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,Sepsis ,medicine.artery ,Intestinal Fistula ,Internal Medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aorta, Abdominal ,Abscess ,Ultrasonography ,Aged, 80 and over ,Vascular Fistula ,Aorta ,business.industry ,030208 emergency & critical care medicine ,General Medicine ,Aortic bifurcation ,medicine.disease ,Abdominal aortic aneurysm ,Heart Arrest ,Surgery ,medicine.anatomical_structure ,cardiovascular system ,Radiology ,medicine.symptom ,Differential diagnosis ,Tomography, X-Ray Computed ,business - Abstract
We report a case of an 81-year-old man, hospitalized for sepsis unresponsive to targeted antibiotic therapy, who underwent abdominal aortic aneurysmectomy with stent placement before 12 years. Point-of-care ultrasound examination showed the presence of a voluminous and inhomogeneous lesion adjacent to the anterior wall of aortic bifurcation with pulsatile flow from the aorta into the lesion, highlighted by Color-Doppler, and peripheral (closely with intestinal loops) floating hyperechoic spots marked by posterior comet tail artifact, suggestive for the presence of air bubbles. The presence of an aortoenteric fistula not excluding in differential diagnosis and the possibility of an abscess of aneurysmatic sac with colonization of gas-producing bacteria were suspected; an abdominal contrast-enhanced computed tomography was requested and it confirmed the suspicion of an aortoenteric fistula. The patient underwent emergency surgical intervention with good technical success (evidence of aorto-appendicular fistula), but he died the day after of cardiac arrest.Descriviamo il caso di un uomo di 81 anni, ricoverato per sepsi non responsiva ad antibioticoterapia mirata, sottoposto 12 anni prima ad aneurismectomia dell'aorta addominale con innesto protesico. L'esame ecografico eseguito al letto mostrava la presenza di una voluminosa formazione disomogenea a livello della parete anteriore della biforcazione aortica, con evidenza, al Color-Doppler, di flusso pulsatile dall'aorta all'interno della lesione, e presenza di spot iperecogeni mobili con artefatto a coda di cometa nella parte più periferica (a stretto contato con le anse intestinali), come per presenza di componente gassosa. Si formulava quindi il sospetto di una fistola aortoenterica, non potendosi escludere, in diagnosi differenziale, una raccolta ascessuale della sacca aneurismatica con colonizzazione di batteri produttori di gas. Veniva richiesta una TC addome urgente con mezzo di contrasto che confermava il sospetto di fistola aorto-enterica; il paziente, veniva sottoposto in urgenza ad intervento chirurgico tecnicamente efficace (riscontro di fistola aorto-appendicolare), ma decedeva nella fase post-operatoria per arresto cardiaco conseguente a infarto miocardico acuto.
- Published
- 2017
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