Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study
Abstract: Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at char...
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Elsevier
2025-02-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924006487 |
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| author | Bruno Fattizzo Alfredo Marchetti Alessandro Bosi Carmelo Gurnari Juri Alessandro Giannotta Giacinto Luca Pedone Elena Rossi Valentina Carrai Andrea Guido Filippo Brioschi Monica Carpenedo Monica Crugnola Domenica Caramazza Livia Leuzzi Monia Marchetti Gabriele Merati Simona Malato Fabrizio Vianello Andrea Patriarca Hussein Awada Marta Bortolotti Marta Canzi Niccolò Bolli Marco Capecchi Frederick Chen Andrea Artoni Jaroslaw P. Maciejewski Wilma Barcellini |
| author_facet | Bruno Fattizzo Alfredo Marchetti Alessandro Bosi Carmelo Gurnari Juri Alessandro Giannotta Giacinto Luca Pedone Elena Rossi Valentina Carrai Andrea Guido Filippo Brioschi Monica Carpenedo Monica Crugnola Domenica Caramazza Livia Leuzzi Monia Marchetti Gabriele Merati Simona Malato Fabrizio Vianello Andrea Patriarca Hussein Awada Marta Bortolotti Marta Canzi Niccolò Bolli Marco Capecchi Frederick Chen Andrea Artoni Jaroslaw P. Maciejewski Wilma Barcellini |
| author_sort | Bruno Fattizzo |
| collection | DOAJ |
| description | Abstract: Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. In this multicentric retrospective observational study, we enrolled 167 adult patients with ITP, followed at 13 centers in Italy, United Kingdom, and the United States. Patients underwent NGS evaluation after a median of 3.6 years from ITP onset, and 83% had received at least 1 therapy line, for a median of 2 lines (range, 0-9); 51 of 167 patients (30%) had at least 1 mutation. After exclusion of germ line variants and polymorphisms, 31 of 167 (18.5%) were defined as having clonal hemopoiesis. Most commonly mutated genes were TET2, DNMT3A, SRSF2, and ASXL1 (median variant allele frequency, 29%); 19 of 31 patients (68%) had high-risk variants, and 8 had multiple mutations. Mutated patients were more frequently older males and showed a shorter time from first to second-line therapy, particularly with thrombopoietin receptor agonist (TPO-RA). Additionally, clonal hematopoiesis was associated with increased thrombotic risk (26% vs 8% in NGS-negative cases; P = .01), independently from TPO-RA exposure, though with an age effect. These data demonstrated the prevalence of clonal hematopoiesis in 18% of adult patients with ITP, which is associated with older age, relapsed/refractory disease, and high risk of thrombotic complications. |
| format | Article |
| id | doaj-art-a850479c34f741beb2ea55e8591ce0ae |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-a850479c34f741beb2ea55e8591ce0ae2025-01-30T05:14:48ZengElsevierBlood Advances2473-95292025-02-0193488495Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter studyBruno Fattizzo0Alfredo Marchetti1Alessandro Bosi2Carmelo Gurnari3Juri Alessandro Giannotta4Giacinto Luca Pedone5Elena Rossi6Valentina Carrai7Andrea Guido8Filippo Brioschi9Monica Carpenedo10Monica Crugnola11Domenica Caramazza12Livia Leuzzi13Monia Marchetti14Gabriele Merati15Simona Malato16Fabrizio Vianello17Andrea Patriarca18Hussein Awada19Marta Bortolotti20Marta Canzi21Niccolò Bolli22Marco Capecchi23Frederick Chen24Andrea Artoni25Jaroslaw P. Maciejewski26Wilma Barcellini27Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, Italy; Correspondence: Bruno Fattizzo, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20100, Milan, Italy;Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, ItalyDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OHFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, ItalyPoliclinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyAOU Azienda Ospedaliero-Universitaria Careggi, Florence, ItalyDepartment of Oncology and Haemato-Oncology, University of Milan, Milan, ItalyFondazione IRCCS San Gerardo dei Tintori, Monza, ItalyNiguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, ItalyHematology Unit, University Hospital of Parma, Parma, ItalyASST Settelaghi, Varese, Varese, ItalySC Oncologia, SS Oncoematologia, PO Fatebenefratelli, ASST Fatebenefratelli Sacco, Milan, ItalyAzienda Ospedaliera Nazionale SS Antonio e Biagio e Cesare Arrigo, Alessandria, ItalyHospital Alessandro Manzoni, ASST Lecco, Lecco, ItalyHematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, ItalyDepartment of Medicine, Division of Hematology, University of Padova, ItalyDivision of Hematology, Department of Translational Medicine, University of Eastern Piedmont and AOU Maggiore della Carità, Novara, ItalyDepartment of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OHFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Division of Hematology, Gruppo Ospedaliero Moncucco, Lugano, SwitzerlandBarts ITP Centre, Royal London Hospital, Bartshealth NHS Trust, London, United Kingdom; Blizard institute, Queen Mary University London, London, United KingdomFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OHFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyAbstract: Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. In this multicentric retrospective observational study, we enrolled 167 adult patients with ITP, followed at 13 centers in Italy, United Kingdom, and the United States. Patients underwent NGS evaluation after a median of 3.6 years from ITP onset, and 83% had received at least 1 therapy line, for a median of 2 lines (range, 0-9); 51 of 167 patients (30%) had at least 1 mutation. After exclusion of germ line variants and polymorphisms, 31 of 167 (18.5%) were defined as having clonal hemopoiesis. Most commonly mutated genes were TET2, DNMT3A, SRSF2, and ASXL1 (median variant allele frequency, 29%); 19 of 31 patients (68%) had high-risk variants, and 8 had multiple mutations. Mutated patients were more frequently older males and showed a shorter time from first to second-line therapy, particularly with thrombopoietin receptor agonist (TPO-RA). Additionally, clonal hematopoiesis was associated with increased thrombotic risk (26% vs 8% in NGS-negative cases; P = .01), independently from TPO-RA exposure, though with an age effect. These data demonstrated the prevalence of clonal hematopoiesis in 18% of adult patients with ITP, which is associated with older age, relapsed/refractory disease, and high risk of thrombotic complications.http://www.sciencedirect.com/science/article/pii/S2473952924006487 |
| spellingShingle | Bruno Fattizzo Alfredo Marchetti Alessandro Bosi Carmelo Gurnari Juri Alessandro Giannotta Giacinto Luca Pedone Elena Rossi Valentina Carrai Andrea Guido Filippo Brioschi Monica Carpenedo Monica Crugnola Domenica Caramazza Livia Leuzzi Monia Marchetti Gabriele Merati Simona Malato Fabrizio Vianello Andrea Patriarca Hussein Awada Marta Bortolotti Marta Canzi Niccolò Bolli Marco Capecchi Frederick Chen Andrea Artoni Jaroslaw P. Maciejewski Wilma Barcellini Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study Blood Advances |
| title | Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study |
| title_full | Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study |
| title_fullStr | Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study |
| title_full_unstemmed | Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study |
| title_short | Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study |
| title_sort | clonal hematopoiesis in patients with autoimmune thrombocytopenia an international multicenter study |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924006487 |
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