What is beyond NPM1 and FLT3 ITD Mutationsas Prognostic Indicators in AML- Experiencefrom a Tertiary Care Centre

ABSTRACT

Introduction: Acute Myeloid Leukaemia (AML) is one of the mostcommon haematological malignancies in adults. Molecular mutationsin AML are major determinants of the patient's response to therapyand outcomes. Nucleophosmin 1 (NPM1) confers a good prognosiswhile fms-like tyrosine kinase-3 gene (FLT3-ITD) is associated witha poor prognosis.Aims &Objectives: To study the prognostic molecular markers andcytogenetics of all newly diagnosed and de novo AML cases andassess the impact of the same on treatment outcome.Materials &Methods: 23 patients with newly diagnosed (adult andpaediatric) de novo AML from Jan 2021 to Aug 2021 at GauhatiMedical College, Guwahati were included in this study. We analysedthe bone marrow aspirates, clinical significance of NPM1, CEBPA,FLT3 (by real time PCR) with disease progression. Cytogenetics bykaryotyping and immunophenotypic parameters were also documented and corelated with disease progression.Result: There were (12/23)52.2% males and (11/23)47.8% female. 2patients (8.7%) were positive for FLT3 and 4(17.4%) were positivefor NPM1. (7/23)30.4% patients had t(8,21) of which 3 had normalkaryotype while 2 patients (8.7%) had turner's genotype(45,X). 4patients (17.4%) expired while receiving Induction chemotherapy, ofwhich one had 45,X,t(8,21)genotype, one had NPM1 mutation andone expired during 3 rd cycle of consolidation due to covid 19pneumonia. 6(26.1%) patients had treatment failure following intensive induction therapy of which 2 had t(8,21) with normalkaryotype(40%) and one had NPM1 mutation with wildtype FLT3.All patients with NPM1 mutation were negative for CD34 andHLADR. All patients with NPM1 and FLT3 uniformly expressed CD33.Conclusions: 3/6 patients had failure of induction in spite of havingstandard risk cytogenetics. So, next generation sequencing (NGS) iswarranted upfront for all diagnosed AML cases. It should now beincorporated as a standard of care in the management of AML. Onepatient with turner's genotype and t(8,21) expired during inductiontherapy, hence, prognostic significance of 45,X needs to be furthervalidated in AML.