WT1 Expression in Peripheral Blood at Diagnosis and During the Course of Early Consolidation Treatment Correlates With Survival in Patients With Intermediate and Poor-Risk Acute Myeloid Leukemia
Abstract
Dynamics of WT1 expression during the course of chemotherapy was tested in 106 cases of intermediate and high-risk acute myeloid leukemia in peripheral blood. High WT1 expression after 2 cycles of chemotherapy was a significant prognostic factor for overall and event-free survival in the whole cohort, as well as in patients treated without allogeneic stem cell transplantation.
Background: Up to 55% of non-APL acute myeloid leukemias (AML) lack a molecular target suitable for standardized disease monitoring. We aimed to evaluate the prognostic significance of WT1 gene expression at early stages of intensive treatment.
Patients and Methods: A total of 10(6) consecutive patients with intermediate and high-risk AML who had WT1 expression at diagnosis >500 copies/10(4) ABL and who achieved remission after 1 to 2 cycles of induction treatment were analyzed. WT1 expression was measured in peripheral blood using a standardized European LeukemiaNet method.
Overexpression was defined as >50 copies/10(4) ABL. The median follow-up was 30 months.
Results: Patients with normal versus high WT1 expression after 2 cycles of chemotherapy had overall survival (OS) at 3 years of 66% versus 41% (P=.01); event-free survival (EFS) 45% versus 22% (P=.01). Prognostic significance of WT1 expression after 2 cycles of treatment was maintained in the group of patients treated with chemotherapy alone without hematopoietic stem cell transplantation in first line treatment (OS 70% vs. 36%, P=.02; EFS 35% vs. 0%, P=.03).
Significant prognostic factors for EFS on multivariate analysis were the achievement of molecular remission (<50 copies of WT1) at any time during treatment (hazard ratio [HR] 0.47, P=.04) and increased WT1 expression after 2 cycles of chemotherapy (HR 2.0, P=.03). Conclusion: Increased WT1 expression after 2 cycles of chemotherapy is a negative prognostic factor for survival.
WT1 remains a valuable molecular marker in AML without any leukemiaspecific mutation, especially if next generation sequencing and/or digital polymerase chain reaction are not routinely available.