A more precise assessment of AML risk and prognosis based on cytogenetic and genetic mutation profiles has classified AML risk into low, intermediate and high risk groups with different molecular genetic profiles. Low risk group: karyotype Inv(16), t(8;21) without 9q- or complex karyotype and t(16;16) and molecular mutations as normal karyotype with NPM1 mutation alone. Intermediate risk group: normal karyotype, +8, -Y, t(9;11) and other karyotypes not in the good and poor groups (<3 abnormalities), molecular mutations as c-kit mutations in t(8;21) or inv(16). High-risk group: -5/5q- or -7/7 q-; t(8;21) with 9q- or complex karyotype; inv(3q); 11q23 abnormal; 20q; 21q; 9q-; t(6;9); t(9;22); 17p abnormal and complex karyotype (≥3 aberrations,) with molecular mutations as normal karyotype with separate FLT3 mutation. Min Zhang, Department of Hematology, Wuhan Union Medical College Hospital
Risk stratification
Genetics
Molecular mutations
Low risk
Inv(16), t(8;21) not with 9q- or complex karyotype , t(16;16)
Normal karyotype with separate NPM1 mutation
Intermediate risk
Normal, +8, -Y, t(9;11), other karyotypes not in good and poor groups (<3 abnormal)
C-KIT at t(8;21) or inv(16)
high risk
-5/5q- or -7/7 q-; t(8;21) with 9q- or complex karyotype; inv(3q); 11q23 abnormal; 20q; 21q; 9q-; t(6;9); t(9;22); 17p abnormal; complex karyotype (≥3 structures + number)
The clinical prognosis of patients in the low-risk, intermediate-risk and high-risk groups is significantly different, and individualized treatment based on the above risk stratification can avoid under- or over-treatment.
For patients in the low-risk group, high-dose cytarabine-based intensive chemotherapy or autologous stem cell transplantation can be used after induction of remission to improve relapse-free survival and mortality. Sibling-to-sibling stem cell transplantation can also be performed for low-risk patients if a fully compatible sibling donor is available.
For intermediate-risk and high-risk patients, due to the presence of residual leukemia cells in the body after remission, it is best to perform allogeneic stem cell transplantation after induction of remission. High-dose chemotherapy plus autologous stem cell transplantation is also possible for some patients in the intermediate risk group for whom no donor can be found. However, patients in the high-risk group are prone to relapse and should preferably undergo allogeneic stem cell transplantation as soon as possible after remission.
Normal karyotype with separate FLT3 mutation