Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers

Autor: Sabine Khalife-Hachem, Khalil Saleh, Florence Pasquier, Christophe Willekens, Anthony Tarabay, Leony Antoun, Thomas Grinda, Cristina Castilla-Llorente, Matthieu Duchmann, Cyril Quivoron, Nathalie Auger, Veronique Saada, Suzette Delaloge, Alexandra Leary, Aline Renneville, Ileana Antony-Debre, Filippo Rosselli, Stéphane De Botton, Flore Salviat, Christophe Marzac, Jean-Baptiste Micol
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: HemaSphere, Vol 5, Iss 9, p e632 (2021)
Druh dokumentu: article
ISSN: 2572-9241
00000000
DOI: 10.1097/HS9.0000000000000632
Popis: Definition of therapy-related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy-related acute myeloid leukemia and therapy-related myelodysplastic syndromes has been proposed. We aimed to describe the molecular landscape of TRMN at diagnosis, among 77 patients with previous gynecologic and breast cancer with a dedicated next-generation sequencing panel covering 74 genes. We investigated the impact of clonal hematopoiesis of indeterminate potential-associated mutations (CHIP-AMs defined as presence at TRMN stage of mutations described in CHIP with a frequency >1%) on overall survival (OS) and the clinical relevance of a modified genetic ontogeny-based classifier that categorized patients in 3 subgroups. The most frequently mutated genes were TP53 (31%), DNMT3A (19%), IDH1/2 (13%), NRAS (13%), TET2 (12%), NPM1 (10%), PPM1D (9%), and PTPN11 (9%). CHIP-AMs were detected in 66% of TRMN patients, with no impact on OS. Yet, patients with CHIP-AM were older and had a longer time interval between solid tumor diagnosis and TRMN. According to our modified ontogeny-based classifier, we observed that the patients with TP53 or PPM1D mutations had more treatment lines and complex karyotypes, the “MDS-like” patients were older with more gene mutations, while patients with “De novo/pan-AML” mutations were younger with more balanced chromosomal translocations. Median OS within each subgroup was 7.5, 14.5, and 25.2 months, respectively, with statistically significant difference in multivariate analysis. These results support the integration of cytogenetic and molecular markers into the future TRMN classification to reflect the biological diversity of TRMN and its impact on outcomes.
Databáze: Directory of Open Access Journals
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