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1. Early CAR− CD4+ T‐lymphocytes recovery following CAR‐T cell infusion: A worse outcome in diffuse large B cell lymphoma

Author

Gambella, Massimiliano, primary, Carlomagno, Simona, additional, Mangerini, Rosa, additional, Colombo, Nicoletta, additional, Parodi, Alessia, additional, Ghiggi, Chiara, additional, Giannoni, Livia, additional, Coviello, Elisa, additional, Setti, Chiara, additional, Luchetti, Silvia, additional, Serio, Alberto, additional, Laudisi, Antonella, additional, Passannante, Monica, additional, Bo, Alessandra, additional, Tedone, Elisabetta, additional, Sivori, Simona, additional, Angelucci, Emanuele, additional, and Raiola, Anna Maria, additional

Published
2024
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2. S217: POST-TRANSPLANT NIVOLUMAB PLUS UNSELECTED AUTOLOGOUS LYMPHOCYTES IN REFRACTORY HODGKIN LYMPHOMA RESULTS IN VERY HIGH REMISSION RATE AND EXCELLENT SURVIVAL AND IT IS ASSOCIATED WITH NK CELL EXPANSION

Author

Guolo, Fabio, primary, Minetto, Paola, additional, Pesce, Silvia, additional, Ballerini, Filippo, additional, Cea, Michele, additional, Greppi, Marco, additional, Bozzo, Matteo, additional, Miglino, Maurizio, additional, Tedone, Elisabetta, additional, Bo, Alessandra, additional, Serio, Alberto, additional, Luchetti, Silvia, additional, Candiani, Simona, additional, Mora, Marco, additional, Agostini, Vanessa, additional, Nozza, Paolo, additional, Del Zotto, Genny, additional, Marcenaro, Emanuela, additional, and Lemoli, Roberto Massimo, additional

Published
2023
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3. Early CAR− CD4+ T‐lymphocytes recovery following CAR‐T cell infusion: A worse outcome in diffuse large B cell lymphoma.

Author

Gambella, Massimiliano, Carlomagno, Simona, Mangerini, Rosa, Colombo, Nicoletta, Parodi, Alessia, Ghiggi, Chiara, Giannoni, Livia, Coviello, Elisa, Setti, Chiara, Luchetti, Silvia, Serio, Alberto, Laudisi, Antonella, Passannante, Monica, Bo, Alessandra, Tedone, Elisabetta, Sivori, Simona, Angelucci, Emanuele, and Raiola, Anna Maria

Published
2024
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4. Wilms Tumor 1 Expression and Pre-emptive Immunotherapy in Patients with Acute Myeloid Leukemia Undergoing an Allogeneic Hemopoietic Stem Cell Transplantation

Author

Di Grazia, Carmen, Pozzi, Sarah, Geroldi, Simona, Grasso, Raffaella, Miglino, Maurizio, Colombo, Nicoletta, Tedone, Elisabetta, Luchetti, Silvia, Lamparelli, Teresa, Gualandi, Francesca, Ibatici, Adalberto, Bregante, Stefania, Van Lint, Maria Teresa, Raiola, Anna Maria, Dominietto, Alida, Varaldo, Riccardo, Galaverna, Federica, Ghiso, Anna, Sica, Simona, and Bacigalupo, Andrea

Published
2016
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5. Improved Outcome of Alternative Donor Transplantations in Patients with Myelofibrosis: From Unrelated to Haploidentical Family Donors

Author

Bregante, Stefania, Dominietto, Alida, Ghiso, Anna, Raiola, Anna Maria, Gualandi, Francesca, Varaldo, Riccardo, Di Grazia, Carmen, Lamparelli, Teresa, Luchetti, Silvia, Geroldi, Simona, Casarino, Lucia, Pozzi, Sarah, Tedone, Elisabetta, Van Lint, Maria Teresa, Galaverna, Federica, Barosi, Giovanni, and Bacigalupo, Andrea

Published
2016
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6. Donor selection for adoptive immunotherapy with NK cells in AML patients: Comparison between analysis of lytic NK cell clones and phenotypical identification of alloreactive NK cell repertoire

Author

Meazza, Raffaella, primary, Ruggeri, Loredana, additional, Guolo, Fabio, additional, Minetto, Paola, additional, Canevali, Paolo, additional, Loiacono, Fabrizio, additional, Ciardelli, Sara, additional, Bo, Alessandra, additional, Luchetti, Silvia, additional, Serio, Alberto, additional, Zannoni, Letizia, additional, Retière, Christelle, additional, Colomar-Carando, Natalia, additional, Parisi, Sarah, additional, Curti, Antonio, additional, Lemoli, Roberto M., additional, and Pende, Daniela, additional

Published
2023
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7. Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated with Expansion and Maturation of NK Cells

Author

Guolo, Fabio, primary, Minetto, Paola, additional, Pesce, Silvia, additional, Ballerini, Filippo, additional, Cea, Michele, additional, Frello, Michela, additional, Garibotto, Matteo, additional, Vernarecci, Chiara, additional, Greppi, Marco, additional, Bozzo, Matteo, additional, Salvetti, Chiara, additional, Todiere, Andrea, additional, Tedone, Elisabetta, additional, Colombo, Nicoletta, additional, Parodi, Alessia, additional, Bo, Alessandra, additional, Carlier, Paolo, additional, Serio, Alberto, additional, Luchetti, Silvia, additional, Dominietto, Alida, additional, Varaldo, Riccardo, additional, Mora, Marco, additional, Agostini, Vanessa, additional, Nozza, Paolo, additional, Marcenaro, Emanuela, additional, del Zotto, Genny, additional, and Lemoli, Roberto Massimo, additional

Published
2022
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9. CD19-Targeted Immunotherapies for Diffuse Large B-Cell Lymphoma

Author

Gambella, Massimiliano, primary, Carlomagno, Simona, additional, Raiola, Anna Maria, additional, Giannoni, Livia, additional, Ghiggi, Chiara, additional, Setti, Chiara, additional, Giordano, Chiara, additional, Luchetti, Silvia, additional, Serio, Alberto, additional, Bo, Alessandra, additional, Falco, Michela, additional, Della Chiesa, Mariella, additional, Angelucci, Emanuele, additional, and Sivori, Simona, additional

Published
2022
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10. Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

Author

Guolo, Fabio, primary, Minetto, Paola, additional, Pesce, Silvia, additional, Ballerini, Filippo, additional, Clavio, Marino, additional, Cea, Michele, additional, Frello, Michela, additional, Garibotto, Matteo, additional, Greppi, Marco, additional, Bozzo, Matteo, additional, Miglino, Maurizio, additional, Passannante, Monica, additional, Marcolin, Riccardo, additional, Tedone, Elisabetta, additional, Colombo, Nicoletta, additional, Mangerini, Rosa, additional, Bo, Alessandra, additional, Ruzzenenti, Maria Rosaria, additional, Carlier, Paolo, additional, Serio, Alberto, additional, Luchetti, Silvia, additional, Dominietto, Alida, additional, Varaldo, Riccardo, additional, Candiani, Simona, additional, Agostini, Vanessa, additional, Ravetti, Jean Louis, additional, Del Zotto, Genny, additional, Marcenaro, Emanuela, additional, and Lemoli, Roberto Massimo, additional

Published
2021
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11. Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Truly Refractory Hodgkin Lymphoma Patients Is Highly Effective and Responses Are Mediated By NK Cells

Author

Guolo, Fabio, Minetto, Paola, Pesce, Silvia, Ballerini, Filippo, Greppi, Marco, Bozzo, Matteo, Cea, Michele, Miglino, Maurizio, Todiere, Andrea, Tedone, Elisabetta, Colombo, Nicoletta, Bò, Alessandra, Serio, Alberto, Luchetti, Silvia, Dominietto, Alida, Varaldo, Riccardo, Candiani, Simona, Mora, Marco, Nozza, Paolo, Del Zotto, Genny, Marcenaro, Emanuela, and Lemoli, Roberto M.

Published
2023
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15. Adoptive Cell Therapy and Immune Check Points Inhibitors As a Salvage Treatment for Patient Affected By Relapsed/Refractory Hodgkin's Lymphoma

Author

Guolo, Fabio, primary, Minetto, Paola, additional, Ballerini, Filippo, additional, Tedone, Elisabetta, additional, Contini, Paola, additional, Mangerini, Rosa, additional, Bo, Alessandra, additional, De Luigi, Maria Carla, additional, Carlier, Paolo, additional, Serio, Alberto, additional, Strada, Paolo, additional, Luchetti, Silvia, additional, Gobbi, Marco, additional, Marcenaro, Emanuela, additional, and Lemoli, Roberto Massimo, additional

Published
2019
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18. Feasibility and Efficacy of Post-Transplant Consolidation Immunotherapy with Nivolumab Supported By the Reinfusion of Unselected Autologous Lymphocytes in Patients Affected By Relapsed/Refractory Hodgkin Lymphoma

Author

Guolo, Fabio, primary, Minetto, Paola, additional, Ballerini, Filippo, additional, Canale, Filippo Antonio, additional, Frello, Michela, additional, Coviello, Elisa, additional, Manconi, Lorenzo, additional, Kunkl, Annalisa, additional, Tedone, Elisabetta, additional, Mangerini, Rosa, additional, Contini, Paola, additional, Fenoglio, Daniela, additional, Miglino, Maurizio, additional, Bo, Alessandra, additional, De Luigi, Maria Carla, additional, Ruzzenenti, Maria Rosaria, additional, Carlier, Paolo, additional, Serio, Alberto, additional, Luchetti, Silvia, additional, Marcenaro, Emanuela, additional, Strada, Paolo, additional, Ravetti, Jean Louis, additional, Gobbi, Marco, additional, and Lemoli, Roberto Massimo, additional

Published
2018
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20. 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

21. 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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22. Allogeneic Transplanst for ACUTE Myeloid Leukemia: Cut Off Levels of WT1 Expression in 207 Patients and Pre-Emptive Therapy of Relapse

Author

Di Grazia, Carmen, primary, Geroldi, Simona, additional, Grasso, Raffaella, additional, Miglino, Maurizio, additional, Colombo, Nicoletta, additional, Tedone, Elisabetta, additional, Luchetti, Silvia, additional, Lamparelli, Teresa, additional, Gualandi, Francesca, additional, Ibatici, Adalberto, additional, Bregante, Stefania, additional, van Lint, Maria Teresa, additional, Raiola, Anna Maria, additional, Dominietto, Alida, additional, Varaldo, Riccardo, additional, Galaverna, Federica, additional, Ghiso, Anna, additional, and Bacigalupo, Andrea, additional

Published
2015
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23. Allogeneic STEM CELL Transplants for Patients with Myelofibrosis: Changes in the Transplant Platform and Improved the Outcome

Author

Bregante, Stefania, primary, Dominietto, Alida, additional, Ghiso, Anna, additional, Raiola, Anna Maria, additional, Gualandi, Francesca, additional, Varaldo, Riccardo, additional, Di Grazia, Carmen, additional, Lamparelli, Teresa, additional, Luchetti, Silvia, additional, Geroldi, Simona, additional, Casarino, Lucia, additional, Pozzi, Sarah, additional, Tedone, Elisabetta, additional, van Lint, Maria Teresa, additional, Galaverna, Federica, additional, Barosi, Gianni, additional, and Bacigalupo, Andrea, additional

Published
2015
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24. CD34+ Selected Cells For The Treatment Of Poor Graft Function Following Allogeneic Stem Cell Transplantation

Author

Stasia, Alessandra, primary, Ghiso, Anna, additional, Raiola, Anna Maria, additional, Galaverna, Federica, additional, Varaldo, Riccardo, additional, Gualandi, Francesca, additional, Dominietto, Alida, additional, Pozzi, Sarah, additional, Luchetti, Silvia, additional, Pogliani, Enrico Maria, additional, and Bacigalupo, Andrea, additional

Published
2013
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25. Donor Lymphocyte Infusions (DLI) Following Haplo Bone Marrow Transplantation (hBMT) with High-Dose of Cyclophosphamide Post-Transplant As Gvhd Prophylaxis

Author

Ghiso, Anna, primary, Raiola, Annamaria, additional, Gualandi, Francesca, additional, Dominietto, Alida, additional, Varaldo, Riccardo, additional, van Lint, Maria Teresa, additional, Bregante, Stefania, additional, Di Grazia, Carmen, additional, Lamparelli, Teresa, additional, Luchetti, Silvia, additional, Geroldi, Simona, additional, Tedone, Elisabetta, additional, and Bacigalupo, Andrea P, additional

Published
2012
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26. Direct Intra-Bone Injection of Unrelated Cord Blood Cells Overcomes the Problem of Delayed Engraftment and Improves the Feasibility of Hematopoietic Transplant in Adult Patients.

Author

Ibatici, Adalberto, primary, Raiola, AnnaMaria, additional, Podesta, Marina, additional, Gualandi, Francesca, additional, Sessarego, Nadia, additional, Parodi, Alessia, additional, Luchetti, Silvia, additional, Pozzi, Sarah, additional, Pinto, Valeria, additional, Piaggio, Giovanna, additional, Gobbi, Marco, additional, Bacigalupo, Andrea, additional, and Frassoni, Francesco, additional

Published
2007
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27. EZH1/2 Inhibitors Favor ILC3 Development from Human HSPC-CD34 + Cells.

Author

Damele, Laura, Amaro, Adriana, Serio, Alberto, Luchetti, Silvia, Pfeffer, Ulrich, Mingari, Maria Cristina, and Vitale, Chiara

Subjects
NUCLEAR proteins, HEMATOLOGIC malignancies, CHEMICAL inhibitors
Abstract

Simple Summary: It has been well-demonstrated that EZH1/2 enzymes are involved not only in tumor development and progression, but also in the regulation of normal hematopoiesis from CD34+-HSPC. Given the crucial role of NK cells in tumor immune surveillance, in this study, we investigated whether EZH1/2 inhibitors can interfere with NK cell differentiation and functional maturation. Our results suggest that EZH1/2 inhibitors push CD56+ precursor proliferation, skewing precursor cell lineage commitment towards ILC3. In recent years, several clinical trials on the use of EZH1/2 inhibitors against solid tumors have been carried out. Since these in vitro observations revealed possible epigenetic mechanisms involved in NK/ILC development, it is important to evaluate patient monitoring of competent NK cells repertoire in order to design appropriate therapeutic protocols. The dysregulation of epigenetic modifications has a well-established role in the development and progression of hematological malignancies and of solid tumors. In this context, EZH1/2 inhibitors have been designed to interfere with EZH1/2 enzymes involved in histone methylation (e.g., H3K27me3), leading to tumor growth arrest or the restoration of tumor suppressor gene transcription. However, these compounds also affect normal hematopoiesis, interfering with self-renewal and differentiation of CD34+-Hematopoietic Stem/Progenitor Cells (HSPC), and, in turn, could modulate the generation of potential anti-tumor effector lymphocytes. Given the important role of NK cells in the immune surveillance of tumors, it would be useful to understand whether epigenetic drugs can modulate NK cell differentiation and functional maturation. CD34+-HSPC were cultured in the absence or in the presence of the EZH1/2 inhibitor UNC1999 and EZH2 inhibitor GSK126. Our results show that UNC1999 and GSK126 increased CD56+ cell proliferation compared to the control condition. However, UNC1999 and GSK 126 favored the proliferation of no-cytotoxic CD56+ILC3, according to the early expression of the AHR and ROR-γt transcription factors. Our results describe novel epigenetic mechanisms involved in the modulation of NK cell maturation that may provide new tools for designing NK cell-based immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2021
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28. 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

29. Early CAR - CD4 + T-lymphocytes recovery following CAR-T cell infusion: A worse outcome in diffuse large B cell lymphoma.

Author

Gambella M, Carlomagno S, Mangerini R, Colombo N, Parodi A, Ghiggi C, Giannoni L, Coviello E, Setti C, Luchetti S, Serio A, Laudisi A, Passannante M, Bo A, Tedone E, Sivori S, Angelucci E, and Raiola AM

Abstract

CAR - CD4 + T cell lymphopenia is an emerging issue following CAR-T cell therapy. We analyzed the determinants of CD4 + T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR-T for diffuse large B-cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric-flow cytometry. Six-month cumulative incidence of CAR - CD4 + T cell recovery (≥200 cells/μL) was 0.43 (95% confidence interval [CI]: 0.28-0.65). Among possible determinants of CD4 + T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16-24.12] p  = 0.016). Higher CD4 + T cell counts resulted with TSA at month-1, -2 and -3. Moderate-to-severe infections were registered with prolonged CD4 + T cell lymphopenia. Early, month-1 CD4 + T cell recovery was associated with a worse outcome in the DLBCL cohort, upheld in a multivariate regression model for overall survival (HR: 4.46 [95% CI: 1.12-17.71], p  = 0.03). We conclude that a faster CAR - CD4 + T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR - CD4 + T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients., Competing Interests: The authors declare no conflicts of interests., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Published
2024
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