High WT1 Expression in 2nd CR of AML Is Predictive for Early Relapse (prospective study)

The Wilms' tumor gene 1 (WT1), which is over-expressed in more than 90% of AML, is a useful marker for monitoring MRD. Quantification of WT1 transcript level in peripheral blood (PB) and bone marrow (BM) at recovery from chemotherapy reliably discriminates patients at different risks of relapse. It is known that WT1 expression may be a marker of future relapse in 1 CR AML patients, after allogenic BMT and WT1 reduction also is a prognostic during induction of the first episode of AML. But there no evidence of WT1 reduction value in AML relapse.

In our prospective study were 10 patients with the first AML relapse and 2nd bone marrow complete remission were studied. High level of WT1 at relapse and achieving 2^nd remission were the main inclusion criteria. Median WT1 level at relapse was 4302,2 (range 540–13184) copies WT1/104 Abl. Monitoring of WT1 level were estimated in patients with median age 36,6 (range from 20 to 64). Median time from the first CR to the relapse was 16,47 months (range from 3 to 51 mo), so there were 6 patients with early relapse and 4 patients with late relapse respectively. Chemotherapy with high dose cytarabine (HiDAC, FLAG) used for 2^nd CR induction.

Only 66,7% (6 patients) demonstrated WT1 normalization. All of patients (n=4) with high WT1 expression in bone marrow remission developed second relapse in a few months, median time to relapse was 4,45 months (range from 2,8 to 7,4 mo). While patients with normal WT1 level in 2^nd remission had relapse free survival 83.3% at 20 months (p=0.048, Fisher exact test, two tailed). Only one of 6 patients developed an extramedullary relapse in 6 months. The groups of patients were comparable to cytogenetic and molecular risks.

We have shown that high WT1 level in 2^nd remission is predictive for early relapse. Thus, high WT1 level in 2^nd remission is an indication for very early stem cell transplantation.

No relevant conflicts of interest to declare.