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Prognostic significance of mutation profile at diagnosis and mutation persistence during disease remission in adult acute myeloid leukaemia patients
Author(s) -
Folta Adam,
Culen Martin,
Jeziskova Ivana,
Herudkova Zdenka,
Tom Nikola,
Hlubinkova Tereza,
Janeckova Veronika,
Durinikova Anna,
Vydra Jan,
Semerad Lukas,
Dvorakova Dana,
Remesova Hana,
Cerovska Ela,
Cetkovsky Petr,
Jindra Pavel,
Szotkowski Tomas,
Zak Pavel,
Mayer Jiri,
Racil Zdenek
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15916
Subject(s) - cebpa , npm1 , medicine , oncology , hematopoietic stem cell transplantation , myeloid leukemia , mutation , myeloid , transplantation , biology , gene , genetics , karyotype , chromosome
Summary 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 (allo HSCT ) within the intermediate cytogenetic risk group patients ( n = 184). The most adverse prognosis was observed in patients with DNMT 3A and FLT 3 ‐ ITD co‐mutation, whose survival could be significantly improved with allo HSCT . In contrast, the most favourable prognosis without any further benefit from allo HSCT was identified in patients with mutations in NPM 1 or CEBPA , after exclusion of the unfavourable prognostic groups defined by mutations in DNMT 3A , RUNX 1 or genes from chromatin/spliceosome group. An additional analysis of 113 diagnosis‐remission paired samples revealed that persistence of non‐ DNMT 3A 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.