High EVI1 Expression Predicts Adverse Outcomes in Children With De Novo Acute Myeloid Leukemia.

ABSTRACT:

Background

A high ecotropic viral integration site 1 (EVI1) expression (EVI1 ^high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1 ^high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1 ^high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China.

Methods

A diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1 ^high, n = 348 for EVI1 ^low).

Results

EVI1 ^high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1 ^high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA, NPM1, or C-KIT mutations. In the univariate Cox regression analysis, EVI1 ^high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1 ^high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1 ^high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1 ^high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45).

Conclusion

It could be concluded that EVI1 ^high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1 ^high AML can benefit from HSCT in CR1 needs to be researched further.

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC8474639 | biostudies-literature |

REPOSITORIES: biostudies-literature