Introduction-About 25% of persons with new-diagnosed acute myeloid leukemia (AML) have normal cytogenetics and no NPM1 or FLT3-ITD mutation. The prognosis and best therapy of these persons is controversial.

Methods-We evaluated 809 consecutive newly diagnosed adult with normal cytogenetics and 231 of whom had no NPM1 or FLT3-ITD mutation identified by targeted regional sequencing. 158 achieved a complete remission within 2 cycles of induction therapy and were assigned to 2 different post-remission strategies: (1) 6 courses of consolidation chemotherapy (N=95); or (2) 2-4 courses of consolidation chemotherapy and an allotransplant (N=63).

Results-In multi-variable analyses a WBC ≥13·6×10E+9/L, mutated IDH2, not having a bi-allelic CEBPA mutation at diagnosis, a positive measurable residual disease (MRD)-test during consolidation and not receiving an allotransplant were independently associated with a higher cumulative incidence of relapse (CIR) and worse event-free survival (EFS). Amongst subjects with IDH2 mutations, non-bi-allelic CEBPA mutations or a positive MRD-test, subjects receiving an allotransplant had a lower 5-year CIR (16% [95% confidence interval, 6, 26%]; vs. 83% [72, 95%]; hazard ratio, HR=8·77 [4·05, 13·49]; P < 0·001) and better 5-year EFS (74% [60, 88%] vs. 15% [5, 25%]; HR=0·16 [0·09, 0·29]; P < 0·001). In contrast, in subjects with none of these adverse predictive variables there was no difference in CIR and EFS between those receiving an allotransplant and those who did not.

Conclusions-Our data suggest a strategy to identify which persons with AML with normal cytogenetics and no NPM1 or FLT3-ITD mutation benefit from an allotransplant.

Trial Registration: Registered in the, NCT01455272 and NCT02185261.

Keywords: Acute myeloid leukemia, mutations, prognosis, targeted regional sequencing, measurable residual disease, risk stratification.


Profs. Guo-Rui Ruan and Xiao-Jun Huang

Peking University Peoples Hospital and Institute of Hematology

No.11 Xi-Zhi-Men South Street, Beijing 100044, China

T 86-10-88324672

F 86-10-88324672


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.