Prognostic impact of early minimal residual disease combined with complete molecular evaluation in acute myeloid leukemia with mutated <i>NPM1</i>: a single center study.
Mara MemoliAlexis GenthonFabrizia FavaleSimona LapusanNatacha JohnsonRosa AdaevaCaroline DeswarteGiorgia BattipagliaFlorent MalardRémy DuléryEolia BrissotAnne BanetZoé Van de WyngaertMohamad MohtyFrançois DelhommeauOllivier LegrandPierre HirschPublished in: Leukemia & lymphoma (2022)
We evaluated prognostic factors in 83 intensively treated adult patients with <i>NPM1</i> mutated AML. Targeted next-generation sequencing revealed high frequency of co-mutations in epigenetic modifiers or proliferation pathways. <i>NPM1</i> minimal residual disease (MRD), assessed in bone marrow by specific polymerase chain reaction after one chemotherapy course, was >0.01% in 50 patients considered poor responders (PR). On multivariate analysis, including all variables with a <i>p</i> value <.1 on univariate analysis, age >60, performance status (PS) ≥1, presence of <i>FLT3</i> mutations, <i>DNMT3A</i>-R882, and PR status, were independently associated with lower leukemia-free survival. Age >60, a previous hematological disease and PR status were independent negative predictive factors for overall survival. In our study, early <i>NPM1</i> MRD was confirmed as an important prognostic factor. All <i>FLT3</i> and <i>DNMT3A</i>-R882 mutations have also an independent prognostic value. We support the rational for in-depth investigations for a better approach in patients who achieving a first complete remission.
Keyphrases
- acute myeloid leukemia
- prognostic factors
- high frequency
- free survival
- allogeneic hematopoietic stem cell transplantation
- dna methylation
- bone marrow
- transcranial magnetic stimulation
- mesenchymal stem cells
- end stage renal disease
- gene expression
- newly diagnosed
- single cell
- ejection fraction
- optical coherence tomography
- genome wide
- chronic kidney disease
- wild type
- locally advanced