Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study

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.

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Publication Details

Journal
Blood Advances
Published
2024-11-13
DOI
https://doi.org/10.1182/bloodadvances.2024014984
Citations
5
Primary Topic
Platelet Disorders and Treatments
Type
article
Field-Weighted Citation Impact
2.27
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article

Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study

Filippo Brioschi, Monica Crugnola, Marta Bortolotti, Valentina Carrai et al.
5 citations
Blood Advances
Platelet Disorders and Treatments
2.27
article

Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study

Filippo Brioschi, Monica Crugnola, Marta Bortolotti, Valentina Carrai, A. Guido, Andrea Artoni, Andrea Patriarca, Simona Malato, Wilma Barcellini, Domenica Caramazza, Niccolò Bolli, Marta Canzi, Carmelo Gurnari, Juri Alessandro Giannotta, Fabrizio Vianello, Giacinto Luca Pedone, Marco Capecchi, Bruno Fattizzo, Monia Marchetti, Hussein Awada, Alfredo Marchetti, Monica Carpenedo, Jaroslaw Pawel Maciejewski, Livia Leuzzi, Frederick Chen, Gabriele Merati, Alessandro Bosi, Elena Rossi
article en
5 citations

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.

Blood AdvancesVol. 9(3)
University of Bergamo (IT), University of Rome Tor Vergata (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Parma (IT), Cleveland Clinic (US), University of Padua (IT), Vita-Salute San Raffaele University (IT), Queen Mary University of London (GB), University of Milan (IT), Barts Health NHS Trust (GB), Ospedale di Circolo e Fondazione Macchi (IT), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), San Raffaele University of Rome (IT), Ospedale Maggiore (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Azienda Ospedaliera San Gerardo (IT), Alessandro Manzoni Hospital (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Fondazione Audiologica Varese (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), ASST Fatebenefratelli Sacco (IT), Piedmont University (US), Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT), Clinica Luganese Moncucco (CH), Aziende Socio Sanitarie Territoriali di Lecco, European Institute of Oncology (IT)
Good health and well-being
Openalex Percentile: Top 11%
Platelet Disorders and Treatments
2.27
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