FLT3‐ITD + DNMT3A mutation

The FLT3 inhibitor gilteritinib was administered for reinduction therapy after failure of chemotherapy with a combination of venetoclax, decitabine, aclarubicin, cytarabine and granulocyte colony-stimulating factor. Similar cases of Sweet syndrome following FLT3 inhibitor therapy for acute myeloid leukemia were reviewed. Attention should be given to this rare complication when FLT3 inhibitors are used for acute myeloid leukemia therapy, and appropriate treatments need to be administered in a timely manner.

NRAS mutations were associated with poor outcome in trisomy AML, whereas DNMT3A and FLT3-ITD mutations had neutral effect. Trisomy AML appeared biologically distinct from CN-AML.

RUNX1 was not an independent prognostic factor for survival. Overall, our findings agree with the updated WHO classification system for AML that AML-RUNX1mut should not be recognized as a distinct AML entity.

Patients were treated by an anthracycline and cytarabine-based or homoharringtonine and cytarabine-based induction chemotherapy regimen and followed by high dose cytarabine as consolidation therapy. A<3log reduction of MRD2 was also another independent poor prognostic factor for survival, which could be improved by allo-HSCT. Meanwhile, the conversion of MRD for NPM1 from negative to positive might be a poor prognostic factor, but it requires to be validated by multivariate analysis.

Induction regimens included DA +/- etoposide (ADE) and FLAG-IDA, with or without Gemtuzumab. Conclusion The "triple hit" (NPM1, DNMT3A and FLT3 ITD) genotype, WT1mut and high WCC were associated with poor outcomes, due to a lower probability of achieving MRD–, and a higher relapse risk from MRD– remission. Survival was improved for patients receiving intensified induction with FLAG-Ida including patients in these high-risk groups.

D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Patients with intermediate cytogenetic risk AML and high antigen expression show poor prognosis even after HSCT in first complete remission, highlighting the need to develop novel therapeutic strategies for these patients. Different immunotherapeutic approaches targeting these antigens are currently being developed by our group, with the hope of identifying novel therapeutic strategies for the treatment of NK triple mutated AML.

Patients with FLT3-ITD and NPM1 mutations have the worst prognosis, where the presence of those mutations was significantly related to overall survival (OS) and EFS. Our study reflects that DNMT3A was not an extremely bad prognostic effect as an independent factor. We can declare according to this study that genetic mutation and variants detection could easily be incorporated into the regimen evaluation of AML patients.

These data suggested PRDM16 expression could be used to predict the outcome of patients with CN-AML. PRDM16 is significantly associated with FLT3-ITD and DNMT3A mutation and WT1 expression and serves as a potential prognostic biomarker in CN-AML.

Our study supports adverse prognostic effect of presence of DNMT3A gene mutation either alone or in the presence of FLT3 and/or NPM1 gene mutations.