Contributions
Abstract: PB1677
Type: Publication Only
Background
Nearly half of acute myeloid leukemia (AML) patients are defined as an intermediate cytogenetic risk, however the patients in this group have greatly varied outcomes and need to be stratified. Apart from gene mutation, abnormal gene expression might also be prognostic, and ecotropic viral integration site 1 (EVI1) expression is a representative. To date, the poor prognostic impact of EVI1 expression in AML has been reported, but almost all studies have been undertaken by European researchers. EVI1 prognostic significance in AML remains to be confirmed in other populations. Furthermore, because the detection protocol and cutoff value selection methodologies differed among studies, the threshold for defining EVI1 high expression remains obscure, which hinders its clinical routine application.
Aims
We investigated the prognostic impact of EVI1 transcript levels in Chinese adult intermediate cytogenetic risk AML (ICR-AML) patients who received chemotherapy only in a single center. The appropriate cutoff values for grouping EVI1 expression were also evaluated.
Methods
A total of 191 adult patients receiving chemotherapy only were included in this study. They were diagnosed as ICR-AML according to morphology, immunophenotyping, cytogenetics and molecular biology. Their bone marrow samples were collected at diagnosis. Real-time quantitative PCR was performed to test EVI1, MLL partial tandem duplicate (MLL-PTD) and WT1 transcripts, and their transcript levels were calculated as the percentage of target transcript copies/ABL copies. NPM1 mutations and FLT3 internal tandem duplication (FLT3-ITD) were individually screened by real-time quantitative PCR and qualitative PCR. 27 normal bone marrow (NBM) samples form volunteers were simultaneously tested EVI1, MLL-PTD and WT1 transcripts. All participants provided written informed consent in accordance with the Declaration of Helsinki.
Results
The upper limit of EVI1 transcript levels in 27 NBM samples was 8.0%. Receiver operating characteristic curve analysis showed that 1.0% (a 0.9-log reduction from the normal limit) was the EVI1 optimal diagnostic cutoff value for significantly differentiating relapse (P=0.049). A total of 23 patients (12%) had EVI1 levels ≥1.0%. EVI1≥1.0% had no impact on complete remission achievement. EVI1≥1.0% was significantly associated with lower 2-year relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) rates in the entire cohort (P=0.0003, 0.0017 and 0.0009), patients with normal karyotypes (n=148, P=0.0032, 0.0047 and 0.0007) and FLT3-ITD (-) patients (n=150, all P<0.0001). Multivariate analysis showed that EVI1≥1.0% and FLT3-ITD (+) were independent adverse prognostic factors for RFS (Table 1), DFS and OS in the entire cohort. In addition, patients with EVI1 between 1.0% and 8.0% had 2-year RFS rates similar to those with EVI1≥8.0% (P=0.16), and both patient groups had significantly higher RFS rates than those with EVI1<1.0%.
HR (95%CI) | P value | |
EVI1 expression | ||
≥1.0% | 4.0 (2.1-7.7) | <0.0001 |
FLT3-ITD | ||
(+) | 3.4 (1.9-6.0) | <0.0001 |
PLT count | ||
<100×10E9/L | 2.1 (1.1-4.3) | 0.030 |
Blast percentage in BM | ||
>65% | 2.1 (1.1-3.6) | 0.017 |
Conclusion
EVI1 transcript levels at diagnosis could further stratify adult ICR-AML, and high EVI1 expression predicts poor outcomes in patients receiving chemotherapy only. The optimal cutoff value which best differentiates patients is different from the normal upper limit.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Acute Myeloid Leukemia, EVI1, chemotherapy
Abstract: PB1677
Type: Publication Only
Background
Nearly half of acute myeloid leukemia (AML) patients are defined as an intermediate cytogenetic risk, however the patients in this group have greatly varied outcomes and need to be stratified. Apart from gene mutation, abnormal gene expression might also be prognostic, and ecotropic viral integration site 1 (EVI1) expression is a representative. To date, the poor prognostic impact of EVI1 expression in AML has been reported, but almost all studies have been undertaken by European researchers. EVI1 prognostic significance in AML remains to be confirmed in other populations. Furthermore, because the detection protocol and cutoff value selection methodologies differed among studies, the threshold for defining EVI1 high expression remains obscure, which hinders its clinical routine application.
Aims
We investigated the prognostic impact of EVI1 transcript levels in Chinese adult intermediate cytogenetic risk AML (ICR-AML) patients who received chemotherapy only in a single center. The appropriate cutoff values for grouping EVI1 expression were also evaluated.
Methods
A total of 191 adult patients receiving chemotherapy only were included in this study. They were diagnosed as ICR-AML according to morphology, immunophenotyping, cytogenetics and molecular biology. Their bone marrow samples were collected at diagnosis. Real-time quantitative PCR was performed to test EVI1, MLL partial tandem duplicate (MLL-PTD) and WT1 transcripts, and their transcript levels were calculated as the percentage of target transcript copies/ABL copies. NPM1 mutations and FLT3 internal tandem duplication (FLT3-ITD) were individually screened by real-time quantitative PCR and qualitative PCR. 27 normal bone marrow (NBM) samples form volunteers were simultaneously tested EVI1, MLL-PTD and WT1 transcripts. All participants provided written informed consent in accordance with the Declaration of Helsinki.
Results
The upper limit of EVI1 transcript levels in 27 NBM samples was 8.0%. Receiver operating characteristic curve analysis showed that 1.0% (a 0.9-log reduction from the normal limit) was the EVI1 optimal diagnostic cutoff value for significantly differentiating relapse (P=0.049). A total of 23 patients (12%) had EVI1 levels ≥1.0%. EVI1≥1.0% had no impact on complete remission achievement. EVI1≥1.0% was significantly associated with lower 2-year relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) rates in the entire cohort (P=0.0003, 0.0017 and 0.0009), patients with normal karyotypes (n=148, P=0.0032, 0.0047 and 0.0007) and FLT3-ITD (-) patients (n=150, all P<0.0001). Multivariate analysis showed that EVI1≥1.0% and FLT3-ITD (+) were independent adverse prognostic factors for RFS (Table 1), DFS and OS in the entire cohort. In addition, patients with EVI1 between 1.0% and 8.0% had 2-year RFS rates similar to those with EVI1≥8.0% (P=0.16), and both patient groups had significantly higher RFS rates than those with EVI1<1.0%.
HR (95%CI) | P value | |
EVI1 expression | ||
≥1.0% | 4.0 (2.1-7.7) | <0.0001 |
FLT3-ITD | ||
(+) | 3.4 (1.9-6.0) | <0.0001 |
PLT count | ||
<100×10E9/L | 2.1 (1.1-4.3) | 0.030 |
Blast percentage in BM | ||
>65% | 2.1 (1.1-3.6) | 0.017 |
Conclusion
EVI1 transcript levels at diagnosis could further stratify adult ICR-AML, and high EVI1 expression predicts poor outcomes in patients receiving chemotherapy only. The optimal cutoff value which best differentiates patients is different from the normal upper limit.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Acute Myeloid Leukemia, EVI1, chemotherapy