Post-remission and pre-allogenic HCT role of WT1 MRD in AML

Chiara Frairia et al. from the University-Hospital Città della Salute e della Scienza, Torino, Italy, retrospectively studied the role of Wilms Tumor Gene 1 (WT1) as a Minimal Residual Disease (MRD) marker in patients with Acute Myeloid Leukemia (AML) after intensive induction chemotherapy and before Allogenic Hematopoietic Cell Transplantation (allo-HCT). The results of the study were published ahead of print in Leukemia Research on 25^th August 2017.

In this retrospective study (NCT02714790), 255 adult patients with untreated AML who were consecutively diagnosed between March 2004 and March 2014 at the University-Hospital Città della Salute e della Scienza were included. Of these, WT1 MRD expression was assessed in the BM samples of AML patients in Complete Remission (CR) after induction (n = 117) and prior to allo-HCT (n = 65) using Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR). Using a cut-off of 350 and 150 BM WT1 copies, the prognostic impact of WT1 was evaluated on survival and pre allo-HCT respectively.

The key results of the study:

• BM WT1 overexpression did not predict response to induction therapy; P = 0.244
• Median Overall Survival (OS) was significantly shorter in patients with post induction WT1 > 350 copies compared to those with ≤ 350 copies; 17 vs 54 months, HR = 1.81, P = 0.05
• 3-year Disease Free Survival (DFS) in patients with WT1 ≤ 350 copies and > 350 copies; 55% vs 15%, HR = 2.81, P < 0.001
• Higher risk of mortality was significantly associated with WT1 > 350 copies; HR = 2.13, P = 0.0018
• 2-year Cumulative Incidence of Relapse (CIR) in patients displaying a pre allo-HCT BM WT1 level of > 150 copies and ≤ 150 copies; 51% vs 22%, P = 0.003

In summary, “BM WT1 overexpression is associated with survival in AML patients in CR after induction and before allo-HCT”.  The authors highlighted that due to the retrospective nature of their study and the small sample size, the role of WT1 detected MRD is still debatable.

The authors concluded that the results of the study suggest “WT1 overexpression might represent an additional MRD tool for risk stratification in patients classified nowadays in CR”.

 Abstract

In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) is still under investigation. The aim of the present retrospective study was to assess the role of Wilms tumor gene 1 (WT1) overexpression in a large monocentric cohort of AML patients. Among 255 enrolled patients, MRD was investigated in those in complete remission (CR) with an available WT1 at baseline (>250 copies) and at two further time-points: after induction (n = 117) and prior allogeneic hematopoietic cell transplantation (allo-HCT), n = 65. Baseline BM WT1 overexpression was not associated with response to induction (p = 0.244). Median overall survival (OS) and disease-free survival (DFS) were significantly shorter in patients with > 350 WT1 copies after induction compared to those with ≤350 (HR for mortality 2.13; 95% CI 1.14–3.97, p = 0.018 and HR for relapse 2.81; 95% CI 1.14–6.93, p = 0.025). Patients with WT1 > 150 copies pre allo-HCT had a significantly higher 2-year cumulative incidence of relapse (CIR) compared to those with WT1 ≤ 150 (HR 4.61; 95% CI 1.72–12.31, p = 0.002). The prognostic role of WT1 overexpression resulted independent from other well-established risk factors. According to these results, WT1 overexpression might represent an additional MRD tool for risk stratification in patients classified nowadays in CR.