Post Induction WT1 MRD Analysis Significantly Predicts Early Relapse in Acute Myeloid Leukemia (AML) Patients

AML patients early relapsing within 12 months, still represents an extremely poor prognosis setting. Cytogenetic and molecular data are not diagnostic in 20-25% of AML patients and intermediate 2 ELN risk category has still an undefined prognosis. Post induction and consolidation MRD might represent a new prognostic factor besides patients and disease characteristics. We have evaluated post induction and consolidation bone marrow mimimal residual disease (MRD) in 126 AML patients (median age: 61.5 years, range: 17-89) with 20 months median follow-up (range 2-79.9). We analysed abnormal leukemia immunophenotype (ALIP) by multiparameter flow cytometry (MPFC) and WT1 by RT-PCR as described by Buccisano et al and Cilloni et al. Cytogenetic, NPM and FLT3 status were performed in 111, 97 and 119 patients respectively, defining the molecular cytogenetic risk in 96 patients. WT1 was +ve in 91/114 patients (70%) at diagnosis (median 1,231.5; range: 2-268,784), in 11/71 (15.5%) post induction (median 1216; range:260-134,633) and in 8/66 (12,1%) post consolidation (median 627.8; range:258-45,338). MPFC MRD was +ve in 33/66 (50%) patients after induction and in 18/48 (37.5%) after consolidation. We analysed 12 month Cumulative Incidence of Relapse (CIR) adjusted by MRD status, patients and disease characteristics. 82/99 patients achieved CR, 40 relapsed in a median of 8 months (1-52 months) 29 within 12 months with 37.5% 1 yr CIR. Patients receiving chemotherapy (38), Autologous (14) and Allogeneic Transplant (39) as post consolidation treatment had 45%, 35% and 30% 1 yr CIR respectively. NPM+FLT3- patients had 25% 1 yr CIR, compared to 25% in NPM-FLT3-, 50% in NPM+FLT3+ and 47% in NPM-FLT3+. Patients with WT1 positive post induction and consolidation had 1 year CIR of 90% and 72.5% respectively. Patients with MPFC positive post induction and consolidation had a 1 year CIR of 48.6% and 44.5% respectively. Multivariate analysis identified post induction WT1 positive status as the main predictor of 1 year CIR. Patients with WT1 positive after induction had a a 15.8 RR of 1 year CIR(p<0.0001) in comparison to WT1 negative patients. Hyperleukocytosis (WBC count >50,000/ml at diagnosis) and age>60 yrs also significantly predicted 1 year CIR with a RR of 7.22 (p=0.002) and 9.1 (p=0.001) respectively. In conclusion WT1 post induction status confirmed its prognostic significance in our series targeting a subset of early relapsing patients with an extremely poor outcome deserving experimental approaches.