CD34 Expression On the Blasts of Bone Marrow Is a Novel Predictor of Poor Prognosis Independent of FlT3-ITD in Acute Myeloid Leukemia with NPM1-Mutation.

Most studies have demonstrated NPM1-mutated acute myeloid leukemia(NPM1m+AML) has a favorable prognosis, especially in the absence of concomitant FLT3-ITD. However, recent studies showed the prognostic heterogeneity of NPM1m+AML. CD34-expression was demonstrated as a poor prognosis factor of adult patients with AML in most previous reports. The strike immunophenotype of NPM1m+AML is regarded as lacking expression of CD34, which accounts for about 75% patients. Whether CD34-expression on the blasts has independent prognostic value in NPM1-m+AML has yet to be clarified. We therefore systematically evaluated the prognostic relevance of CD34 status in the context of NPM1mutation status and clinical features in 71 patients treated at our institution.

Seventy-one NPM1m+AML patients were retrospectively analyzed in our center. Immunophenotype of AML were detected by 4 color flow cytometry. NPM1 mutation and FLT3-mutation were detected by PCR.

The percentage of CD34-expressed blasts of bone marrow ranged from 0.01% to 93.2%. Patients with CD34 expression>7%(according to ROC analysis) had a lower complete remission(CR) rate after 1 course induction, disease-free survival(DFS) and overall survival(OS) compared those with CD34-expression¡Ü7%(CR, 46.4% vs. 81.4%, p=0.0038; 3 years DFS, 26.2% vs. 68.5%, p=0.001; 3 years OS, 24.4% vs.69.1%, p<0.0001). Multivariate analysis revealed CD34-expression as an independent prognostic factor independent of FlT3-ITD for relapse, DFS and OS. We established a new prognostic model based on CD34 and FLT3 status at diagnosis, which could allow dissection of NPM1m+AML into prognostically different three subgroups: CD34>7% and FLT3-ITD, CD34>7%or FLT3-ITD, CD34¡Ü7% and FLT3-WT(3 years DFS of 0 vs. 58.3% vs. 77%, p=0.002; OS of 0 vs. 59.1% vs. 79.9%, p<0.0001 ) .

We demonstrated for the first time, that CD34-expression on the blasts is a novel poor predictor independent of FlT3-ITD in patients with NPM1-mutation, and established a new prognostic model based on CD34 and FLT3 status at diagnosis, which could allow immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.

Figure 1.

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The disease-free survival and overall survival in patients of patients with CD34 expression>7% and ¡Ü7% in entire cohort (A and B)

Figure 1.

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The disease-free survival and overall survival in patients of patients with CD34 expression>7% and ¡Ü7% in entire cohort (A and B)

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Figure 2.

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The disease-free survival and overall survival of prognostically different three subgroups of CD34>7% andFLT3-ITD, CD34>7%or FLT3-ITD and CD34¡Ü7% and FLT3-WT in entire patients with NPM1-mutation(A and B)

Figure 2.

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The disease-free survival and overall survival of prognostically different three subgroups of CD34>7% andFLT3-ITD, CD34>7%or FLT3-ITD and CD34¡Ü7% and FLT3-WT in entire patients with NPM1-mutation(A and B)

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No relevant conflicts of interest to declare.