Allo-SCT, MRD Negativity Associated With Better Outcomes in AML With Certain Mutations

Study findings shed a light on the role of minimal residual disease (MRD) status and type of postremission therapy in the prognosis of patients with intermediate-risk acute myeloid leukemia (AML) who do not have FLT3-ITD, NPM1, and biallelic CEBPA mutations.

Hoping to offer a better understanding of appropriate postremission therapy (PRT) for patients with intermediate-risk acute myeloid leukemia (IR-AML), researchers are detailing their findings on clinical and molecular factors that impact prognosis in certain patients with AML.

Their retrospective findings, recently published in Hematology, shed light on the role of minimal residual disease (MRD) status and type of PRT in the prognosis of patients with IR-AML who do not have FLT3-ITD, NPM1, and biallelic CEBPA mutations.

According to the researchers, these findings have relevant implications because the role of molecular genetics is increasingly being utilized in prognostic assessment of patients, particularly in IR-AML.

“In general, NPM1mut/FLT3-ITDmut-neg or CEBPAdm provides a good prognosis for IR-AML, whereas IR- AML with FLT3-ITDmut has a poor prognosis,” explained the researchers. “For the subgroup of patients with IR-AML negative for NPM1mut, CEBPAdm, and FLT3-ITDmut (here referred to as NPM1mut-negCEBPAdm-negFLT3-ITDneg AML), the risk–benefit ratio of [allogeneic hematopoietic stem cell transplantation] is poorly defined.”

The study included 64 patients with intermediate-risk disease, of which 28 had NPM1mut-negCEBPAdm-negFLT3-ITDneg AML that had achieved a complete response.

Altough 17 of the patients analyzed in the study received postremission chemotherapy (PR-CT), 11 received allogeneic hematopoietic stem cell transplantation (allo-HSCT), which was associated with improved overall survival (OS) and relapse-free survival (RFS), as well as reduced cumulative incidence of relapse (CIR). Independently, allo-HSCT was also associated with favorable OS.

According to the researchers, the increased survival benefit seen with allo-HSCT over PR-CT may be explained by the lower risk of relapse—an independent adverse factor for prognosis—associated with allo-HSCT, as well as its better CIR.

Unsurprisingly, MRD negativity prior to PRT was independently associated with favorable OS.

“Thus, we further performed a subgroup analysis. For patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML, allo-HSCT also improved the OS and RFS of patients who obtained MRDpos or MRDneg compared with PR-CT (OS, P = .012 and P = .036, respectively; RFS, P = .030 and P = .047, respectively),” wrote the researchers.

The lack of molecular profiling data for some of the participants and the small sample size were noted as study limitations for generalizing interpretation of these findings.


Zheng W-S, Hu Y-L, Guan L-X, Peng B, Wang S-Y. The effect of the detection of minimal residual disease for the prognosis and the choice of post-remission therapy of intermediate-risk acute myeloid leukemia without FLT3-ITD, NPM1 and biallelic CEBPA mutations. Hematology. 2021;26(1):179-185. doi:10.1080/16078454.2021.1880753