Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial
Abstract: Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive next-generation sequencing–based analysis of the M-CH mutational landscape at baseli...
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Elsevier
2025-04-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925000175 |
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| author | Simone Ragaini Anna Galli Elisa Genuardi Martina Gandossini Beatrice Alessandria Aurora Maria Civita Andrea Evangelista Enrico Amaducci Vittorio Stefoni Federica Cavallo Filippo Ballerini Benedetta Puccini Daniele Vallisa Mariagrazia Michieli Anna Pascarella Angelo Palmas Caterina Patti Elisa Lucchini Maria Grazia Careddu Michele Merli Massimiliano Postorino Carola Boccomini Monica Balzarotti Vittorio Ruggero Zilioli Maria Gomes da Silva Benedetto Bruno Ettore Rizzo Marco Ladetto Luca Malcovati Simone Ferrero |
| author_facet | Simone Ragaini Anna Galli Elisa Genuardi Martina Gandossini Beatrice Alessandria Aurora Maria Civita Andrea Evangelista Enrico Amaducci Vittorio Stefoni Federica Cavallo Filippo Ballerini Benedetta Puccini Daniele Vallisa Mariagrazia Michieli Anna Pascarella Angelo Palmas Caterina Patti Elisa Lucchini Maria Grazia Careddu Michele Merli Massimiliano Postorino Carola Boccomini Monica Balzarotti Vittorio Ruggero Zilioli Maria Gomes da Silva Benedetto Bruno Ettore Rizzo Marco Ladetto Luca Malcovati Simone Ferrero |
| author_sort | Simone Ragaini |
| collection | DOAJ |
| description | Abstract: Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive next-generation sequencing–based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi MCL0208 phase 3 trial, evaluating lenalidomide maintenance vs observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young patients with MCL. Overall, 254 of 300 (85%) enrolled patients (median age, 57 years [range, 32-66]) had a baseline sample available for CH analysis. Using stringent criteria, at least 1 mutation involving M-CH candidate genes was described in 34 patients (13%), with DNMT3A being the most frequently mutated gene (54%). After a median follow-up of 7 years, the presence of large CH clones (variant allele frequency of ≥10%) predicted worse progression-free survival (hazard ratio [HR], 2.93; 95% confidence interval [CI] 1.36-6.31; P = .006) and overall survival (HR, 3.02 [1.21-7.55]; P = .018) compared with patients with CH. Importantly, the competing risks analysis demonstrates that the worse clinical outcome associated with M-CH large clones is linked to MCL progression (P < .05). Moreover, large M-CH clones showed longer time to hematological recovery after ASCT than the remaining cohort (P = .026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in patients with MCL. This trial was registered at www.clinicaltrialsregister.eu as EudraCT (2009-012807-25) and www.ClinicalTrials.gov as #NCT02354313. |
| format | Article |
| id | doaj-art-7697d2a2988b411fa689de0b5d478cec |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Blood Advances |
| spelling | doaj-art-7697d2a2988b411fa689de0b5d478cec2025-08-20T02:08:31ZengElsevierBlood Advances2473-95292025-04-01981805181510.1182/bloodadvances.2024014948Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trialSimone Ragaini0Anna Galli1Elisa Genuardi2Martina Gandossini3Beatrice Alessandria4Aurora Maria Civita5Andrea Evangelista6Enrico Amaducci7Vittorio Stefoni8Federica Cavallo9Filippo Ballerini10Benedetta Puccini11Daniele Vallisa12Mariagrazia Michieli13Anna Pascarella14Angelo Palmas15Caterina Patti16Elisa Lucchini17Maria Grazia Careddu18Michele Merli19Massimiliano Postorino20Carola Boccomini21Monica Balzarotti22Vittorio Ruggero Zilioli23Maria Gomes da Silva24Benedetto Bruno25Ettore Rizzo26Marco Ladetto27Luca Malcovati28Simone Ferrero29Department of Molecular Biotechnologies and Health, University of Torino, Torino, Italy; Hematology Unit, Azienda Ospedaliero-Universitaria “Città della Salute e della Scienza di Torino,” Torino, ItalyDepartment of Hematology Oncology, IRCCS San Matteo Hospital Foundation, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, ItalyDepartment of Molecular Biotechnologies and Health, University of Torino, Torino, ItalyDepartment of Hematology Oncology, IRCCS San Matteo Hospital Foundation, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, ItalyDepartment of Molecular Biotechnologies and Health, University of Torino, Torino, ItalyDepartment of Molecular Biotechnologies and Health, University of Torino, Torino, ItalyUnit of Clinical Epidemiology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza and Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte, Torino, ItalyDepartment of Molecular Biotechnologies and Health, University of Torino, Torino, Italy; Hematology Unit, Azienda Ospedaliero-Universitaria “Città della Salute e della Scienza di Torino,” Torino, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Bologna, ItalyDepartment of Molecular Biotechnologies and Health, University of Torino, Torino, Italy; Hematology Unit, Azienda Ospedaliero-Universitaria “Città della Salute e della Scienza di Torino,” Torino, ItalyIRCCS Ospedale Policlinico San Martino, Genova, ItalyHematology Unit, Careggi University Hospital, Firenze, ItalyHematology Unit, Department of Oncology and Hematology, Guglielmo da Saliceto Hospital, Piacenza, ItalyHigh Dose Chemotherapy and Cellular Therapies Unit, IRCCS Centro di Riferimento Oncologico di Aviano, Aviano, ItalyHematology Unit, Ospedale dell'Angelo, Mestre-Venezia, ItalyStruttura Complessa Ematologia, Ospedale San Francesco, Azienda Sanitaria Locale Nuoro, Nuoro, ItalyDepartment of Hematology I, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo, ItalyUnità Complessa Operativa Ematologia, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, ItalyEmatologia, AOU Sassari, Sassari, ItalyDipartimento di Oncologia ed Ematologia, Università degli Studi di Milano, Policlinico di Milano, Ospedale Maggiore, Fondazione IRCCS Ca Granda, Milano, ItalyHematology Unit, Department of Biomedicine and Prevention, University Tor Vergata, Roma, ItalyStuttura Complessa Ematologia, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, ItalyUnità Operativa di Ematologia, IRCCS Humanitas Research Hospital, Milano, ItalyDivision of Hematology, Azienda Socio-Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milano, ItalyDepartment of Hematology, Portuguese Institute of Oncology, Lisbon, PortugalDepartment of Molecular Biotechnologies and Health, University of Torino, Torino, Italy; Hematology Unit, Azienda Ospedaliero-Universitaria “Città della Salute e della Scienza di Torino,” Torino, ItalyenGenome, Pavia, ItalyHematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy; Department of Translational Medicine, University of Eastern Piedmont, Alessandria, ItalyDepartment of Hematology Oncology, IRCCS San Matteo Hospital Foundation, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, ItalyDepartment of Molecular Biotechnologies and Health, University of Torino, Torino, Italy; Hematology Unit, Azienda Ospedaliero-Universitaria “Città della Salute e della Scienza di Torino,” Torino, Italy; Correspondence: Simone Ferrero, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Via Genova 3, 10126 Torino, Italy;Abstract: Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive next-generation sequencing–based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi MCL0208 phase 3 trial, evaluating lenalidomide maintenance vs observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young patients with MCL. Overall, 254 of 300 (85%) enrolled patients (median age, 57 years [range, 32-66]) had a baseline sample available for CH analysis. Using stringent criteria, at least 1 mutation involving M-CH candidate genes was described in 34 patients (13%), with DNMT3A being the most frequently mutated gene (54%). After a median follow-up of 7 years, the presence of large CH clones (variant allele frequency of ≥10%) predicted worse progression-free survival (hazard ratio [HR], 2.93; 95% confidence interval [CI] 1.36-6.31; P = .006) and overall survival (HR, 3.02 [1.21-7.55]; P = .018) compared with patients with CH. Importantly, the competing risks analysis demonstrates that the worse clinical outcome associated with M-CH large clones is linked to MCL progression (P < .05). Moreover, large M-CH clones showed longer time to hematological recovery after ASCT than the remaining cohort (P = .026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in patients with MCL. This trial was registered at www.clinicaltrialsregister.eu as EudraCT (2009-012807-25) and www.ClinicalTrials.gov as #NCT02354313.http://www.sciencedirect.com/science/article/pii/S2473952925000175 |
| spellingShingle | Simone Ragaini Anna Galli Elisa Genuardi Martina Gandossini Beatrice Alessandria Aurora Maria Civita Andrea Evangelista Enrico Amaducci Vittorio Stefoni Federica Cavallo Filippo Ballerini Benedetta Puccini Daniele Vallisa Mariagrazia Michieli Anna Pascarella Angelo Palmas Caterina Patti Elisa Lucchini Maria Grazia Careddu Michele Merli Massimiliano Postorino Carola Boccomini Monica Balzarotti Vittorio Ruggero Zilioli Maria Gomes da Silva Benedetto Bruno Ettore Rizzo Marco Ladetto Luca Malcovati Simone Ferrero Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial Blood Advances |
| title | Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial |
| title_full | Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial |
| title_fullStr | Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial |
| title_full_unstemmed | Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial |
| title_short | Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial |
| title_sort | large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma results from the fil mcl0208 clinical trial |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925000175 |
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