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17-gene LSC score: mutations and outcome in AML
Next, we tested the prognostic impact of the 17-gene LSC score in multivariable analyses (Table 3). In younger patients, the 17-gene LSC score remained prognostically significant for all clinical endpoints, namely CR, DFS, and OS. In older patients, the score was prognostically signifi- cant only for OS, but it was not significant in the final models for achievement of a CR or DFS (Table 3).
Prognostic impact of the 17-gene leukemia stem cell score in the context of the current European LeukemiaNet classification
To test the prognostic value of the 17-gene LSC score in the context of the current 2017 ELN classification, we clas- sified all patients according to the published guidelines into ELN Favorable-, Intermediate- and Adverse-risk groups.1 In both age cohorts, we found significant differ- ences in the ELN risk-group distribution between patients with 17-genelow and 17-genehigh scores (P<0.001 for younger and P=0.009 for older patients). Among the younger patients, two-thirds with a 17-genelow score were classified as having Favorable-risk, whereas 14% and 17% were classified as having, respectively, Intermediate- and Adverse-risk. On the other hand, younger patients with a 17-genehigh score were most frequently classified in the
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Adverse-risk group (41%), followed by the Intermediate- (32%) and Favorable-risk (26%) groups. Among the older patients, the majority in both the 17-genelow and 17-genehigh score groups were classified in the Adverse-risk group (40% and 63%, respectively) (Online Supplementary Table S5), followed by Favorable- (36%) and Intermediate- (24%) risk groups in the 17-genelow group and by equal numbers for Favorable-risk (18%) and Intermediate-risk (18%) groups in the 17-genehigh group.
Next, we tested whether the 17-gene LSC score can be used to refine the prognostic impact of the ELN classifica- tion. Among younger patients, we found that the 17-gene LSC score could refine the ELN classification for the ELN Favorable- and Adverse-risk groups, but not for the Intermediate-risk group. Younger patients with a 17- genelow score in the ELN Favorable-risk group had higher CR rates (P<0.001) (Table 2) and longer DFS (P=0.008) (Figure 3A) and OS (P<0.001) (Figure 3B) than the 17- genehigh patients. Likewise, younger Adverse-risk patients with a 17-genelow score had higher CR rates (P=0.004) (Table 2), and longer DFS (P<0.001) (Figure 3E) and OS (P<0.001) (Figure 3F). On the other hand, among younger patients in the Intermediate-risk group, there was no sig- nificant difference in CR rates (Table 2) or DFS (P=0.08)
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Figure 2. Differences in outcome between patients with low and those with high 17-gene leukemic stem cell scores. (A) Disease-free survival (DFS) and (B) overall survival (OS) of younger adult patients (aged <60 years) according to the 17-gene leukemia stem cell (LSC) score. (C) DFS and (D) OS of older patients (aged ≥60 years) according to the 17-gene LSC score.
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