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6. Prognostic impact of somatic mutations on time to first treatment: Results of targeted next‐generation sequencing in 211 patients with early stage chronic lymphocytic leukemia

Author

Varettoni, Marzia, primary, Orlandi, Ester, additional, Zibellini, Silvia, additional, Rossi, Marianna, additional, Gentile, Massimo, additional, Flospergher, Elena, additional, Ferretti, Virginia V., additional, Rizzo, Ettore, additional, Della Porta, Matteo G., additional, Rattotti, Sara, additional, Cavalloni, Chiara, additional, Bergamini, Fabio, additional, Cristinelli, Caterina, additional, Fabbri, Nicole, additional, Gallì, Anna, additional, and Arcaini, Luca, additional

Published
2021
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7. Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies

Author

Varettoni, Marzia, primary, Ferrari, Angela, additional, Frustaci, Anna M., additional, Ferretti, Virginia V., additional, Rizzi, Rita, additional, Motta, Marina, additional, Piazza, Francesco, additional, Merli, Michele, additional, Benevolo, Giulia, additional, Visco, Carlo, additional, Laurenti, Luca, additional, Ferrero, Simone, additional, Gentile, Massimo, additional, Del Fabro, Vittorio, additional, Abbadessa, Antonio, additional, Klersy, Catherine, additional, Musto, Pellegrino, additional, Fabbri, Nicole, additional, Deodato, Marina, additional, Dogliotti, Irene, additional, Greco, Corinna, additional, Corbingi, Andrea, additional, Luminari, Stefano, additional, and Arcaini, Luca, additional

Published
2020
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8. Circulating endothelial cells in COVID‐19

Author

Nizzoli, Maria E., primary, Merati, Gabriele, additional, Tenore, Annamaria, additional, Picone, Cristina, additional, Consensi, Erica, additional, Perotti, Luciano, additional, Ferretti, Virginia V., additional, Sambo, Margherita, additional, Di Sabatino, Antonio, additional, Iotti, Giorgio A., additional, Arcaini, Luca, additional, Bruno, Raffaele, additional, and Belliato, Mirko, additional

Published
2020
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9. Corrigendum: The Italian Mastocytosis Registry: 6-year experience from a hospital-based registry (Future Oncology (2018) 14:26 (2713-2723) DOI: 10.2217/fon-2018-0291)

Author

Merante, Serena, Ferretti, Virginia V., Elena, Chiara, Brazzelli, Valeria, Zanotti, Roberta, Neri, Iria, Maglicane, Diomira, Fortina, Anna Belloni, Ingeborg, Forer, Pastorello, Elide A., Pieri, Lisa, Papayannidis, Cristina, Mauro, Marina, Grifoni, Federica, Minelli, Roberto, Guggiari, Elena, Difonzo, Elisa, Bocchia, Monica, Caroppo, Francesca, Di Nuzzo, Sergio, Elli, Elena Maria, Rondoni, Michaela, Ciccocioppo, Rachele, Di Stefano, Michele, Bossi, Grazia, Boveri, Emanuela, Bonadonna, Patrizia, Giona, Fiorina, Valent, Peter, and Triggiani, Massimo

Published
2019

10. A risk‐stratification model based on the initial concentration of the serum monoclonal protein andMYD 88mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenström macroglobulinaemia or other lymphoproliferative disorders

Author

Varettoni, Marzia, primary, Zibellini, Silvia, additional, Boveri, Emanuela, additional, Klersy, Catherine, additional, Candido, Chiara, additional, Rattotti, Sara, additional, Ferretti, Virginia V., additional, Defrancesco, Irene, additional, Mangiacavalli, Silvia, additional, Nizzoli, Maria E., additional, Flospergher, Elena, additional, Zerbi, Caterina, additional, Bergamini, Fabio, additional, Benvenuti, Pietro, additional, Brociner, Marco, additional, Merati, Gabriele, additional, Paulli, Marco, additional, and Arcaini, Luca, additional

Published
2019
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11. Facing erythrocytosis: Results of an international physician survey

Author

Rumi, Elisa, primary, McMullin, Mary F., additional, Harrison, Claire, additional, Ellis, Martin H., additional, Barzilai, Merav, additional, Sarid, Nadav, additional, Mesa, Ruben, additional, Paoli, Chiara, additional, Angona, Anna, additional, Sant'Antonio, Emanuela, additional, Ferretti, Virginia V., additional, Cavalloni, Chiara, additional, Casetti, Ilaria C., additional, Trotti, Chiara, additional, and Barbui, Tiziano, additional

Published
2019
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12. The Italian Mastocytosis Registry: 6-year experience from a hospital-based registry

Author

Merante, Serena, primary, Ferretti, Virginia V, additional, Elena, Chiara, additional, Brazzelli, Valeria, additional, Zanotti, Roberta, additional, Neri, Iria, additional, Magliacane, Diomira, additional, Belloni Fortina, Anna, additional, Ingeborg, Forer, additional, Pastorello, Elide A, additional, Pieri, Lisa, additional, Papayannidis, Cristina, additional, Mauro, Marina, additional, Grifoni, Federica, additional, Minelli, Roberto, additional, Guggiari, Elena, additional, Difonzo, Elisa, additional, Bocchia, Monica, additional, Caroppo, Francesca, additional, Di Nuzzo, Sergio, additional, Elli, Elena Maria, additional, Rondoni, Michela, additional, Ciccocioppo, Rachele, additional, Di Stefano, Michele, additional, Bossi, Grazia, additional, Boveri, Emanuela, additional, Bonadonna, Patrizia, additional, Giona, Fiorina, additional, Valent, Peter, additional, and Triggiani, Massimo, additional

Published
2018
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13. High‐dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by the EBMT Lymphoma Working Party and FIL‐GITMO

Author

Avivi, Irit, primary, Arcaini, Luca, additional, Ferretti, Virginia V., additional, Boumendil, Ariane, additional, Finel, Hervé, additional, Milone, Giuseppe, additional, Zaja, Francesco, additional, Liliana, Devizzi, additional, Musso, Maurizio, additional, Didier, Blaise, additional, Bachy, Emmanuel, additional, Wattad, Mohammed, additional, Nicolas‐Virelizier, Emmanuelle, additional, Gramatzki, Martin, additional, Bourhis, Jean‐Henri, additional, Caillot, Denis, additional, Haenel, Anette, additional, Held, Gerhard, additional, Thieblemont, Catherine, additional, Jindra, Pavel, additional, Pohlreich, David, additional, Guilhot, François, additional, Kroschinsky, Frank, additional, Wahlin, Björn, additional, Scheid, Christof, additional, Ifrah, Norbert, additional, Berthou, Christian, additional, Dreger, Peter, additional, Montoto, Silvia, additional, and Conconi, Annarita, additional

Published
2018
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14. Sequential evaluation of CALR mutant burden in patients with myeloproliferative neoplasms

Author

Cavalloni, Chiara, primary, Rumi, Elisa, additional, Ferretti, Virginia V., additional, Pietra, Daniela, additional, Roncoroni, Elisa, additional, Bellini, Marta, additional, Ciboddo, Michele, additional, Casetti, Ilaria C., additional, Landini, Benedetta, additional, Fugazza, Elena, additional, Troletti, Daniela, additional, Astori, Cesare, additional, and Cazzola, Mario, additional

Published
2017
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15. A risk‐stratification model based on the initial concentration of the serum monoclonal protein and MYD88 mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenström macroglobulinaemia or other lymphoproliferative disorders

Author

Varettoni, Marzia, Zibellini, Silvia, Boveri, Emanuela, Klersy, Catherine, Candido, Chiara, Rattotti, Sara, Ferretti, Virginia V., Defrancesco, Irene, Mangiacavalli, Silvia, Nizzoli, Maria E., Flospergher, Elena, Zerbi, Caterina, Bergamini, Fabio, Benvenuti, Pietro, Brociner, Marco, Merati, Gabriele, Paulli, Marco, and Arcaini, Luca

Subjects
MONOCLONAL gammopathies, LYMPHOPROLIFERATIVE disorders, BLOOD proteins, G proteins, DISEASE risk factors, CONFIDENCE intervals
Abstract

Summary: IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenström macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1–2% per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow‐up of 83 months (1214 person‐years), 15 patients (8·5%) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). The rate of progression was 1·32% per year (95% confidence interval [CI] 0·80–2·20). The serum monoclonal protein concentration and the MYD88 mutation were independent risk factors for progression (Hazard ratio [HR] 23·3, 95% CI 2·0–273·3, P = 0·012 and HR 24·4, 95% CI 2·2–275·3, P = 0·010, respectively). The cumulative incidence of progression, while considering death as a competing event, was 11·6% at 5 years and 38·0% at 10 years in MYD88‐mutated patients with a serum monoclonal protein of 10 g/l or higher, as compared with 0% at 5 years and 1·1% at 10 years for patients with none or one risk factor. This risk‐stratification model is able to identify a subset of patients with IgM MGUS at high risk of progression to WM or LPD who deserve a lifelong follow‐up. [ABSTRACT FROM AUTHOR]

Published
2019
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16. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis

Author

Rumi, Elisa, Harutyunyan, Ashot S., Pietra, Daniela, Milosevic, Jelena D., Casetti, Ilaria C., Bellini, Marta, Them, Nicole C.C., Cavalloni, Chiara, Ferretti, Virginia V., Milanesi, Chiara, Berg, Tiina, Sant'Antonio, Emanuela, Boveri, Emanuela, Pascutto, Cristiana, Astori, Cesare, Kralovics, Robert, and Cazzola, Mario

Published
2014
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17. Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem-cell transplantation

Author

Della Porta, Matteo G., Galli, Anna Maria, Bacigalupo, Andrea, Zibellini, Silvia, Bernardi, Massimo, Rizzo, Ettore, Allione, Bernardino, Van Lint, Maria Teresa, Pioltelli, Pietro, Marenco, Paola, Bosi, Alberto, Voso, Maria Teresa, Sica, Simona, Cuzzola, Mariella, Angelucci, Emanuele, Rossi, Marianna, Ubezio, Marta, Malovini, Alberto, Limongelli, Ivan, Ferretti, Virginia V., Spinelli, Orietta, Tresoldi, Cristina, Pozzi, Sarah, Luchetti, Silvia, Pezzetti, Laura, Catricalà, Silvia, Milanesi, Chiara, Riva, Alberto, Bruno, Benedetto, Ciceri, Fabio, Bonifazi, Francesca, Bellazzi, Riccardo, Papaemmanuil, Elli, Santoro, Armando, Alessandrino, Emilio P., Rambaldi, Alessandro, Cazzola, Mario, Bacigalupo, Andrea (ORCID:0000-0002-9119-567X), Sica, Simona (ORCID:0000-0003-2426-3465), Della Porta, Matteo G., Galli, Anna Maria, Bacigalupo, Andrea, Zibellini, Silvia, Bernardi, Massimo, Rizzo, Ettore, Allione, Bernardino, Van Lint, Maria Teresa, Pioltelli, Pietro, Marenco, Paola, Bosi, Alberto, Voso, Maria Teresa, Sica, Simona, Cuzzola, Mariella, Angelucci, Emanuele, Rossi, Marianna, Ubezio, Marta, Malovini, Alberto, Limongelli, Ivan, Ferretti, Virginia V., Spinelli, Orietta, Tresoldi, Cristina, Pozzi, Sarah, Luchetti, Silvia, Pezzetti, Laura, Catricalà, Silvia, Milanesi, Chiara, Riva, Alberto, Bruno, Benedetto, Ciceri, Fabio, Bonifazi, Francesca, Bellazzi, Riccardo, Papaemmanuil, Elli, Santoro, Armando, Alessandrino, Emilio P., Rambaldi, Alessandro, Cazzola, Mario, Bacigalupo, Andrea (ORCID:0000-0002-9119-567X), and Sica, Simona (ORCID:0000-0003-2426-3465)

Abstract

Purpose: The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various combinations of somatic mutations are associated with different clinical phenotypes and outcomes. Whether the genetic basis of MDS influences the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) is unclear. Patients and Methods: We studied 401 patients with MDS or acute myeloid leukemia (AML) evolving from MDS (MDS/AML). We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. We then analyzed the impact of mutations on the outcome of HSCT. Results: Overall, 87% of patients carried one or more oncogenic mutations. Somatic mutations of ASXL1, RUNX1, and TP53 were independent predictors of relapse and overall survival after HSCT in both patients with MDS and patients with MDS/AML (P values ranging from.003 to.035). In patients with MDS/AML, gene ontology (ie, secondary-type AML carrying mutations in genes of RNA splicing machinery, TP53-mutated AML, or de novo AML) was anindependent predictor of posttransplantation outcome (P =.013). The impact of ASXL1, RUNX1, and TP53 mutations on posttransplantation survival was independent of the revised International Prognostic Scoring System (IPSS-R). Combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Accounting for various combinations of IPSS-R risk and somatic mutations, the 5-year probability of survival after HSCT ranged from 0% to 73%. Conclusion: Somatic mutation in ASXL1, RUNX1, or TP53 is independently associated with unfavorable outcomes and shorter survival after allogeneic HSCT for patients with MDS and MDS/AML. Accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.

Published
2016

18. Clinical Effects of Driver Somatic Mutations on the Outcomes of Patients With Myelodysplastic Syndromes Treated With Allogeneic Hematopoietic Stem-Cell Transplantation

Author

Della Porta, Matteo G., primary, Gallì, Anna, additional, Bacigalupo, Andrea, additional, Zibellini, Silvia, additional, Bernardi, Massimo, additional, Rizzo, Ettore, additional, Allione, Bernardino, additional, van Lint, Maria Teresa, additional, Pioltelli, Pietro, additional, Marenco, Paola, additional, Bosi, Alberto, additional, Voso, Maria Teresa, additional, Sica, Simona, additional, Cuzzola, Mariella, additional, Angelucci, Emanuele, additional, Rossi, Marianna, additional, Ubezio, Marta, additional, Malovini, Alberto, additional, Limongelli, Ivan, additional, Ferretti, Virginia V., additional, Spinelli, Orietta, additional, Tresoldi, Cristina, additional, Pozzi, Sarah, additional, Luchetti, Silvia, additional, Pezzetti, Laura, additional, Catricalà, Silvia, additional, Milanesi, Chiara, additional, Riva, Alberto, additional, Bruno, Benedetto, additional, Ciceri, Fabio, additional, Bonifazi, Francesca, additional, Bellazzi, Riccardo, additional, Papaemmanuil, Elli, additional, Santoro, Armando, additional, Alessandrino, Emilio P., additional, Rambaldi, Alessandro, additional, and Cazzola, Mario, additional

Published
2016
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21. CALRexon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis

Author

Rumi, Elisa, Harutyunyan, Ashot S., Pietra, Daniela, Milosevic, Jelena D., Casetti, Ilaria C., Bellini, Marta, Them, Nicole C.C., Cavalloni, Chiara, Ferretti, Virginia V., Milanesi, Chiara, Berg, Tiina, Sant'Antonio, Emanuela, Boveri, Emanuela, Pascutto, Cristiana, Astori, Cesare, Kralovics, Robert, and Cazzola, Mario

Abstract

Somatic mutations in the calreticulin (CALR) gene were recently discovered in patients with sporadic essential thrombocythemia (ET) and primary myelofibrosis (PMF) lacking JAK2and MPLmutations. We studied CALRmutation status in familial cases of myeloproliferative neoplasm. In a cohort of 127 patients, CALRindels were identified in 6 of 55 (11%) subjects with ET and in 6 of 20 (30%) with PMF, whereas 52 cases of polycythemia vera had nonmutated CALR. All CALRmutations were somatic, found in granulocytes but not in T lymphocytes. Patients with CALR-mutated ET showed a higher platelet count (P= .017) and a lower cumulative incidence of thrombosis (P= .036) and of disease progression (P= .047) compared with those with JAK2(V617F). In conclusion, a significant proportion of familial ET and PMF nonmutated for JAK2carry a somatic mutation of CALR.

Published
2014
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22. High-dose therapy and autologous stem cell transplantation in marginal zone lymphomas: A retrospective study by the EBMT Lymphoma Working Party and FIL-GITMO

Author

Virginia Valeria Ferretti, Christof Scheid, Frank Kroschinsky, Ariane Boumendil, Gerhard Held, Denis Caillot, Björn E. Wahlin, Norbert Ifrah, Jean Bourhis, Mohammed Wattad, Maurizio Musso, David Pohlreich, Catherine Thieblemont, Peter Dreger, Pavel Jindra, Emmanuelle Nicolas-Virelizier, Anette Haenel, Irit Avivi, Martin Gramatzki, Blaise Didier, Silvia Montoto, Giuseppe Milone, Devizzi Liliana, Christian Berthou, Luca Arcaini, François Guilhot, Emmanuel Bachy, Francesco Zaja, Annarita Conconi, Herve Finel, Avivi, Irit, Arcaini, Luca, Ferretti, Virginia V., Boumendil, Ariane, Finel, Hervé, Milone, Giuseppe, Zaja, Francesco, Liliana, Devizzi, Musso, Maurizio, Didier, Blaise, Bachy, Emmanuel, Wattad, Mohammed, Nicolas-Virelizier, Emmanuelle, Gramatzki, Martin, Bourhis, Jean-Henri, Caillot, Deni, Haenel, Anette, Held, Gerhard, Thieblemont, Catherine, Jindra, Pavel, Pohlreich, David, Guilhot, Françoi, Kroschinsky, Frank, Wahlin, Björn, Scheid, Christof, Ifrah, Norbert, Berthou, Christian, Dreger, Peter, Montoto, Silvia, Conconi, Annarita, Tel Aviv Sourasky Medical Center [Te Aviv], Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Lymphoma Working Party, Paris (EBMT), Oncohematology Unit, Oncology Department La Maddalena, Centre Léon Bérard [Lyon], 2nd Medical Department, University Hospital Schleswig-Holstein Campus Kiel, Division of Stem Cell Transplantation and, Institut Gustave Roussy (IGR), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Instituto de Pesquisas Meteorológicas (IPMet), Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Department of Hematology and Oncology [Pilsen, Czech Republic], Charles University Hospital Pilsen, Charles University Hospital, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department I of Internal Medicine, University of Cologne, Hematology Department, Université d'Angers (UA), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Department of Medicine V, Universität Heidelberg [Heidelberg], AOU Maggiore della Carità, Division of Hematology, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Autologous transplant, [SDV]Life Sciences [q-bio], Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Chemoimmunotherapy, Marginal zone lymphoma, Mucosa-associated lymphoid tissue lymphoma, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Cumulative incidence, Treatment Failure, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, MALT lymphoma, Lymphoma, B-Cell, Marginal Zone, Hematology, Middle Aged, Prognosis, medicine.disease, Survival Analysis, 3. Good health, Lymphoma, Transplantation, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Rituximab, business, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract

IF 5.128; International audience; The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non‐transformed nodal, extra‐nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1–8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy‐based high‐dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub‐group and more transplants performed in recent years in the other sub‐groups. After a median follow‐up of 5 years, 5‐year cumulative incidence of relapse/progression and non‐relapse mortality were 38% and 9%, respectively. Five‐year event‐free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five‐year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.

Published
2018
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23. Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem-cell transplantation

Author

Cristina Tresoldi, Mariella Cuzzola, Orietta Spinelli, Mario Cazzola, Andrea Bacigalupo, Silvia Luchetti, Ettore Rizzo, Silvia Zibellini, Laura Pezzetti, Silvia Catricalà, Benedetto Bruno, Marianna Rossi, Marta Ubezio, Simona Sica, Chiara Milanesi, Maria Teresa Voso, Emilio Paolo Alessandrino, Riccardo Bellazzi, Anna Gallì, Sarah Pozzi, Armando Santoro, Virginia Valeria Ferretti, Massimo Bernardi, Emanuele Angelucci, Alessandro Rambaldi, Alberto Bosi, Pietro Pioltelli, Paola Marenco, Ivan Limongelli, Fabio Ciceri, Matteo G. Della Porta, Alberto Malovini, Elli Papaemmanuil, Maria Teresa Van Lint, Francesca Bonifazi, Bernardino Allione, Alberto Riva, Della Porta, Matteo G., Gallì, Anna, Bacigalupo, Andrea, Zibellini, Silvia, Bernardi, Massimo, Rizzo, Ettore, Allione, Bernardino, Van Lint, Maria Teresa, Pioltelli, Pietro, Marenco, Paola, Bosi, Alberto, Voso, Maria Teresa, Sica, Simona, Cuzzola, Mariella, Angelucci, Emanuele, Rossi, Marianna, Ubezio, Marta, Malovini, Alberto, Limongelli, Ivan, Ferretti, Virginia V., Spinelli, Orietta, Tresoldi, Cristina, Pozzi, Sarah, Luchetti, Silvia, Pezzetti, Laura, Catricalà, Silvia, Milanesi, Chiara, Riva, Alberto, Bruno, Benedetto, Ciceri, Fabio, Bonifazi, Francesca, Bellazzi, Riccardo, Papaemmanuil, Elli, Santoro, Armando, Alessandrino, Emilio P., Rambaldi, Alessandro, and Cazzola, Mario

Subjects
Oncology, medicine.medical_specialty, Cancer Research, Myeloid, Somatic cell, medicine.medical_treatment, Hematopoietic stem cell transplantation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, business.industry, Myelodysplastic syndromes, Myeloid leukemia, ORIGINAL REPORTS, medicine.disease, Transplantation, Haematopoiesis, Settore MED/15 - MALATTIE DEL SANGUE, medicine.anatomical_structure, RUNX1, chemistry, 030220 oncology & carcinogenesis, Immunology, business, 030215 immunology
Abstract

Purpose The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various combinations of somatic mutations are associated with different clinical phenotypes and outcomes. Whether the genetic basis of MDS influences the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) is unclear. Patients and Methods We studied 401 patients with MDS or acute myeloid leukemia (AML) evolving from MDS (MDS/AML). We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. We then analyzed the impact of mutations on the outcome of HSCT. Results Overall, 87% of patients carried one or more oncogenic mutations. Somatic mutations of ASXL1, RUNX1, and TP53 were independent predictors of relapse and overall survival after HSCT in both patients with MDS and patients with MDS/AML (P values ranging from .003 to .035). In patients with MDS/AML, gene ontology (ie, secondary-type AML carrying mutations in genes of RNA splicing machinery, TP53-mutated AML, or de novo AML) was an independent predictor of posttransplantation outcome (P = .013). The impact of ASXL1, RUNX1, and TP53 mutations on posttransplantation survival was independent of the revised International Prognostic Scoring System (IPSS-R). Combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Accounting for various combinations of IPSS-R risk and somatic mutations, the 5-year probability of survival after HSCT ranged from 0% to 73%. Conclusion Somatic mutation in ASXL1, RUNX1, or TP53 is independently associated with unfavorable outcomes and shorter survival after allogeneic HSCT for patients with MDS and MDS/AML. Accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.

Published
2016

24. Clinical course and outcome of essential thrombocythemia and prefibrotic myelofibrosis according to the revised WHO 2016 diagnostic criteria.

Author

Rumi E, Boveri E, Bellini M, Pietra D, Ferretti VV, Sant'Antonio E, Cavalloni C, Casetti IC, Roncoroni E, Ciboddo M, Benvenuti P, Landini B, Fugazza E, Troletti D, Astori C, and Cazzola M

Abstract

The recently revised World Health Organization (WHO) classification of myeloid neoplasms recognizes prefibrotic myelofibrosis (prePMF) as a distinct entity, characterized by well-defined histopathologic features together with minor clinical criteria (leukocytes, anemia, increased LDH, splenomegaly). The aim of the study was to examine the clinical relevance of distinguishing prePMF from essential thrombocythemia (ET). We identified in our database all patients affected with ET, prePMF and primary myelofibrosis (PMF) diagnosed according to 2008 WHO criteria with a bone marrow fibrosis grade 0-1 at diagnosis and one DNA sample to define the mutational status. The bone marrow morphology of all 404 identified patients was reviewed by an expert pathologist and patients were reclassified according to the 2016 WHO criteria. After reclassification, our cohort included 269 ET, 109 prePMF, and 26 myeloproliferative neoplasm unclassificable. In comparison with ET, patients with prePMF had higher leukocyte count, lower hemoglobin level, higher platelet count, higher LDH values, and higher number of circulating CD34-positive cells; they showed more frequently splenomegaly (all P values < ·001). CALR mutations were more frequent in prePMF than in ET (35·8% vs 17·8%, P < ·001). PrePMF patients had shorter overall survival ( P < ·001) and a trend to a higher incidence of leukemic evolution ( P ·067) compared to ET patients, while they did not differ in terms of thrombotic and bleeding complications. In conclusion, ET and prePMF diagnosed according to 2016 WHO criteria are two entities with a different clinical phenotype at diagnosis and a different clinical outcome., Competing Interests: CONFLICTS OF INTEREST Authors do not have competing financial interests.

Published
2017
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25. Impact of mutational status on pregnancy outcome in patients with essential thrombocytemia.

Author

Rumi E, Bertozzi I, Casetti IC, Roncoroni E, Cavalloni C, Bellini M, Sant'Antonio E, Gotti M, Ferretti VV, Milanesi C, Peroni E, Pietra D, Astori C, Randi ML, and Cazzola M

Subjects
Adult, Female, Humans, Pregnancy, Pregnancy Complications, Hematologic pathology, Pregnancy Complications, Hematologic physiopathology, Thrombocytopenia pathology, Thrombocytopenia physiopathology, Pregnancy Complications, Hematologic genetics, Pregnancy Outcome, Thrombocytopenia genetics
Published
2015
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26. The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection.

Author

Arcaini L, Rossi D, Lucioni M, Nicola M, Bruscaggin A, Fiaccadori V, Riboni R, Ramponi A, Ferretti VV, Cresta S, Casaluci GM, Bonfichi M, Gotti M, Merli M, Maffi A, Arra M, Varettoni M, Rattotti S, Morello L, Guerrera ML, Sciarra R, Gaidano G, Cazzola M, and Paulli M

Subjects
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, DNA-Binding Proteins, Female, Follow-Up Studies, Hepacivirus isolation & purification, Hepatitis C mortality, Hepatitis C pathology, Hepatitis C virology, Humans, Lymphoma, Large B-Cell, Diffuse mortality, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse virology, Male, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local virology, Polymerase Chain Reaction, Prognosis, RNA-Binding Proteins, Survival Rate, Hepatitis C genetics, Homeodomain Proteins genetics, Lymphoma, Large B-Cell, Diffuse genetics, Mutation genetics, Neoplasm Recurrence, Local genetics, Nuclear Proteins genetics, Receptor, Notch1 genetics, Receptor, Notch2 genetics
Abstract

Hepatitis C virus has been found to be associated with B-cell non-Hodgkin lymphomas, mostly marginal zone lymphomas and diffuse large B-cell lymphoma. Deregulation of signaling pathways involved in normal marginal zone development (NOTCH pathway, NF-κB, and BCR signaling) has been demonstrated in splenic marginal zone lymphoma. We studied mutations of NOTCH pathway signaling in 46 patients with hepatitis C virus-positive diffuse large B-cell lymphoma and in 64 patients with diffuse large B-cell lymphoma unrelated to HCV. NOTCH2 mutations were detected in 9 of 46 (20%) hepatitis C virus-positive patients, and NOTCH1 mutations in 2 of 46 (4%). By contrast, only one of 64 HCV-negative patients had a NOTCH1 or NOTCH2 mutation. The frequency of the NOTCH pathway lesions was significantly higher in hepatitis C virus-positive patients (P=0.002). The 5-year overall survival was 27% (95%CI: 5%-56%) for hepatitis C virus-positive diffuse large B-cell lymphoma patients carrying a NOTCH pathway mutation versus 62% (95%CI: 42%-77%) for those without these genetic lesions. By univariate analysis, age over 60 years, NOTCH2 mutation, and any mutation of the NOTCH pathway (NOTCH2, NOTCH1, SPEN) were associated with shorter overall survival. Mutation of the NOTCH pathway retained an independent significance (P=0.029). In conclusion, a subset of patients with hepatitis C virus-positive diffuse large B-cell lymphoma displays a molecular signature of splenic marginal zone and has a worse clinical outcome., (Copyright© Ferrata Storti Foundation.)

Published
2015
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