Prognostic Impact of the Detection of the WT1 Gene mRNA with Peripheral Blood in Adult Acute Myeloid Leukemia (AML).

Background: Approximately 70–80% of all newly diagnosed patients with adult AML achieve a complete remission (CR). However, only about one third of those pts remain free of disease for more than 5 years. It is therefore important to predict which pts are most likely to suffer a relapse and thus perform alternative treatments such as stem cell transplantation in order to improve the prognosis of AML. We evaluated the impact of the detection of Wilms’ tumor gene1 (WT1) mRNA in the peripheral blood on the prognosis of AML pts.

Patients and Methods: From June 1, 2001 to October 30, 2003 a study was performed on 191 pts with AML which evaluated the clinical usefulness of a WT1 mRNA assay kit for the early detection of relapse in AML pts (submitted in Rinsho Ketsueki). From these 191 pts, we selected the subjects for this study. All selected subjects achieved a complete remission, and also had their WT1 expression analyzed after consolidation therapy. The pts were excluded if they had received a stem cell transplantation before relapse. The WT1 mRNA levels were determined using the WT1 mRNA assay kit (Otsuka Pharmaceutical Co. Ltd) in accordance with the standard operating procedures using peripheral blood. The lower limit of detection was 50 copy/μgRNA. Therefore, less than 50 copy/μgRNA was judged as negative. All induction, consolidation and maintenance therapies were performed according to institutional standards.

Results: Of 118 pts who achieved a complete remission, 50 pts (median age: 56 yrs 22–86) were evaluable. Their median WT1 mRNA levels before induction therapy was 48327 copy/μgRNA (137–329185). The WT1 mRNA levels at diagnosis did not correlate with either the relapse rate, DFS or OS, respectively. After CR, the WT1 mRNA level ranged from <50 copy/μg to 30732 copy/μgRNA. Thirty-four (69.4%) pts were positive and 15 pts (30.6%) were negative for the WT1 mRNA. The relapse rate of the positive pts and of the negative pts was 73.5% and 40.0% (P=0.0248 sensitivity=80.6 % specificity=50.0%), respectively. The OS rate at 3 years was 53.1% in the positive pts and 79.0% in the negative pts (P=0.1227), respectively. The DFS rate at 3 years was 30.0% in the positive pts and 60.0 % in the negative pts (P=0.0906), respectively. After consolidation therapy, the WT1 mRNA level ranged from <50 copy/μgRNA to 49174 copy/μgRNA. The WT1 positive pts numbered only 15 pts (32.6%) and the negative pts numbered 31 (67.4%). The relapse rate of the positive pts and the negative pts was 80.0% and 54.8% (P=0.0974), respectively. The OS of rate at 3 years was 42.8% in the positive pts and 69.8% in the negative pts (P=0.0381), respectively. The DFS rate at 3 years was 20.0% in the positive pts and 50.0% in the negative pts (P=0.0116). The rate of relapse within 1 year was 73.3% in the positive pts and only 33.3% in the negative pts (P= 0.0116).

Conclusion: This study shows that the detection of the WT1 mRNA in the peripheral blood after treatment closely correlated with the prognosis in AML.