Prognostic significance of mutation profile at diagnosis and mutation persistence during disease remission in adult acute myeloid leukaemia patients

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Authors

FOLTA Adam ČULEN Martin JEŽÍŠKOVÁ Ivana HERUDKOVÁ Zdeňka TOM Nikola HLUBINKOVÁ Tereza JANEČKOVÁ Veronika ĎURINÍKOVÁ Anna VYDRA Jan SEMERÁD Lukáš DVOŘÁKOVÁ Dana REMEŠOVÁ Hana CEROVSKÁ Ela CETKOVSKÝ Petr JINDRA Pavel SZOTKOWSKI Tomáš ŽÁK Pavel MAYER Jiří RÁČIL Zdeněk

Year of publication 2019
Type Article in Periodical
Magazine / Source British journal of haematology
MU Faculty or unit

Faculty of Medicine

Citation
Web http://dx.doi.org/10.1111/bjh.15916
Doi http://dx.doi.org/10.1111/bjh.15916
Keywords acute myeloid leukaemia; next generation sequencing; persistent mutations; prognostic markers; survival
Description In this multi-centre study, we analysed the prognostic impact of mutations in 19 genes associated with myeloid malignancies in 258 newly diagnosed acute myeloid leukaemia patients (aged 19-70 years) undergoing intensive therapy. We identified five patient groups with different prognostic risks and different benefits from allogeneic hematopoietic stem cell transplantation (alloHSCT) within the intermediate cytogenetic risk group patients (n = 184). The most adverse prognosis was observed in patients with DNMT3A and FLT3-ITD co-mutation, whose survival could be significantly improved with alloHSCT. In contrast, the most favourable prognosis without any further benefit from alloHSCT was identified in patients with mutations in NPM1 or CEBPA, after exclusion of the unfavourable prognostic groups defined by mutations in DNMT3A, RUNX1 or genes from chromatin/spliceosome group. An additional analysis of 113 diagnosis-remission paired samples revealed that persistence of non-DNMT3A mutations (above 2% VAF) represented a further negative prognostic factor. The proposed model offers a possible molecular stratification and treatment guidance for intermediate cytogenetic risk group patients.
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