Measurable Residual Disease Monitoring in Acute Myeloid Leukemia with t(8;21)(q22;q22.1): Results of the AML Study Group.
We performed serial measurable residual disease (MRD) monitoring in bone marrow (BM) and peripheral blood (PB) samples of 155 intensively treated patients with RUNX1-RUNX1T1-positive AML using an RT-qPCR-based assay with a sensitivity of up to 10-6 We assessed both reduction of RUNX1-RUNX1T1 transcript levels and achievement of MRD negativity (MRDneg) for impact on prognosis. Achievement of MR2.5 (>2.5 log reduction) after treatment cycle 1 and achievement of MR3.0 after treatment cycle 2 were significantly associated with a reduced risk of relapse (P=0.034 and P=0.028, respectively). After completion of therapy, achievement of MRDneg in both, BM and PB, was an independent favorable prognostic factor for cumulative incidence of relapse (4-year CIR BM: 17% vs 36%, P=0.021; PB: 23% vs 55%; P=0.001) and overall survival (4-year OS rate BM: 93% vs 70%, P=0.007; PB: 87% vs 47%; P<0.0001). Finally, during follow-up serial RT-qPCR analyses allowed prediction of relapse in 77% of patients exceeding a cut-off value of 150 RUNX1-RUNX1T1 transcript levels in BM, and in 84% of patients exceeding a value of 50 RUNX1-RUNX1T1 transcript levels in PB. KIT mutation was a significant factor predicting for lower CR rate and inferior outcome, but its prognostic impact was outweighed by RUNX1-RUNX1T1 transcript levels during treatment. Virtually all relapses occurred within one year after end of treatment with a very short latency from molecular to morphologic relapse, necessitating MRD assessment at short intervals during this time period. Based on our data we here propose a refined practical guideline for MRD assessment in RUNX1-RUNX1T1-positive AML.