WT1 expression as a marker of minimal residual disease, predicts outcome in acute myeloid leukaemia when measured at post-consolidation

Abstract

Aims (1) Validate and establish a WT1 expression assay from peripheral blood and bone marrow. (2) Investigate prognostic relevance of WT1 expression levels at: diagnosis, post-induction and post-consolidation. Methods The study is prospective and longitudinal, in which WT1 expression from 107 patients with de novo acute myeloid leukaemia (AML) are measured from bone marrow ( WT1 _bm) and peripheral blood ( WT1 _pb) at various clinical time points. Results The cohort had a median age 56 years, 56% male, and 96 patients were treated with curative intent, achieving complete response (CR) in 79%, refractory disease in 7% and 14% induction death. At median follow-up time of 36 months, the median leukaemia free survival (LFS) was 12 months and median overall survival (OS) was 24 months. Median WT1 _pb level at diagnosis was 4558 and varied according to marrow blast percentage ( p = 0.022). Multi-variate analysis showed increased WT1 _pb at diagnosis is predictive of decreased LFS ( p = 0.033). Lower post-consolidation WT1 _pb significantly correlated with better LFS when measured as a continuous variable ( p = 0.006) or undetected versus detected (p = 0.02) and continued to be significant in multivariate analysis. Discussion A correlation between WT1 expression levels and known risk factors for early relapse is demonstrated. In the minimal residual disease setting, detectable WT1 levels in peripheral blood post-induction and post-consolidation predicted very poor leukaemia free survival.