Genetic Profiles and Risk Stratification in Adult De Novo Acute Myeloid Leukaemia in Relation to Age, Gender, and Ethnicity: A Study from Malaysia.

Angeli Ambayya,Rosline Hassan,Sarina Sulong,Jameela Sathar,Anthony V Moorman,Jeyanthy Eswaran

doi:10.3390/ijms23010258

Abstract

Hitherto, no data describing the heterogeneity of genetic profiles and risk stratifications of adult acute myeloid leukaemia (AML) in Southeast Asia are reported. This study assessed genetic profiles, Moorman’s hierarchical classification, and ELN 2017-based risk stratifications in relation to age, gender, and ethnicity in Malaysian adult AML patients. A total of 854 AML patients: male (52%), female (48%) were recruited comprising three main ethnic groups: Malays (59%), Chinese (32%) and Indians (8%). Of 307 patients with abnormal karyotypes: 36% exhibited translocations; 10% deletions and 5% trisomies. The commonest genotype was FLT3-ITD-NPM1wt (276/414; 66.7%). ELN 2017 risk stratification was performed on 494 patients, and 41% were classified as favourable, 39% as intermediate and 20% as adverse groups. More females (47%) were in the favourable risk group compared to males (37%), whereas adverse risk was higher in patients above 60 (24%) of age compared to below 60 (18%) patients. We observed heterogeneity in the distribution of genetic profiles and risk stratifications between the age groups and gender, but not among the ethnic groups. Our study elucidated the diversity of adult AML genetic profiles between Southeast Asians and other regions worldwide.

Highlights

Diagnostic cytogenetic profiles, known as karyotypes, have been the most important predictors of outcomes in acute myeloid leukaemia over the last three decades
As proposed by Martens et al in 2010 [1], cytogenetic aberrations are identifiable in 50% to 60% of newly diagnosed acute myeloid leukaemia (AML) patients, this tool still serves as a powerful prognostic indicator for AML
Studies have revealed geographical diversity in cytogenetic aberrations in haematological malignancies, no comprehensive studies encompass the multi-ethnic population in Southeast Asia [12,13,14,16,18,26,27]

Summary

Introduction

Diagnostic cytogenetic profiles, known as karyotypes, have been the most important predictors of outcomes in acute myeloid leukaemia over the last three decades. Karyotypic analysis in younger patients allows prognostication of AML patients into favourable, intermediate, and adverse risk groups as recommended by the European LeukemiaNet (ELN) and the UK Medical Research Council (MRC) [2,3]. Other chromosomal aberrations, including trisomies and normal karyotypes, are categorised as an intermediate-risk group [4,5,6,7]. AML is characterised by profound biologic divergence, including the distribution, but not the spectrum of chromosomal aberrations [9]. Favourable risk aberrations are relatively uncommon in older patients, in contrast to normal and complex karyotypes. Older patients are commonly known to have a poorer prognosis and present with high-risk cytogenetic abnormalities and preceding myelodysplastic phase or secondary leukaemia [10]. It is axiomatic that dismal prognosis for the older patients is typical as they present with other comorbidities at diagnosis and express multidrug resistance with lower response to chemotherapy [9]

Methods

Results

Conclusion