Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study
Year: 2024
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood Advances
Authors: 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
Institutions: University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Rome Tor Vergata, Cleveland Clinic, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliero-Universitaria Careggi, Azienda Ospedaliera San Gerardo, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, University of Parma, Ospedale di Circolo e Fondazione Macchi, Aziende Socio Sanitarie Territoriale dei Sette Laghi, ASST Fatebenefratelli Sacco, Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Alessandro Manzoni Hospital, Aziende Socio Sanitarie Territoriali di Lecco, IRCCS Ospedale San Raffaele, University of Padua, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Azienda Ospedaliero Universitaria Maggiore della Carita, Queen Mary University of London, Barts Health NHS Trust, Royal London Hospital, Blizard Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funder: Ministero della Salute
OpenAlex ID: W4404315417