Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): Results from 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-RUNX1T1¹ AML, using a qRT-PC–based assay with a sensitivity of up to 102⁶. We assessed both reduction of RUNX1-RUNX1T1 transcript levels (TLs) and achievement of MRD negativity (MRD²) for impact on prognosis. Achievement of MR^2.5 (>2.5 log reduction) after treatment cycle 1 and achievement of MR^3.0 after treatment cycle 2 were significantly associated with a reduced risk of relapse (P 5 .034 and P 5 .028, respectively). After completion of therapy, achievement of MRD2 in both BM and PB was an independent, favorable prognostic factor in cumulative incidence of relapse (4-year cumulative incidence relapse: BM, 17% vs 36%, P 5 .021; PB, 23% vs 55%, P 5 .001) and overall survival (4-year overall survival rate BM, 93% vs 70%, P 5 .007; PB, 87% vs 47%, P < .0001). Finally, during follow-up, serial qRT-PCR analyses allowed prediction of relapse in 77% of patients exceeding a cutoff value of 150 RUNX1-RUNX1T1 TLs in BM, and in 84% of patients exceeding a value of 50 RUNX1-RUNX1T1 TLs in PB. The KIT mutation was a significant factor predicting a lower CR rate and inferior outcome, but its prognostic impact was outweighed by RUNX1-RUNX1T1 TLs during treatment. Virtually all relapses occurred within 1 year after the 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 propose a refined practical guideline for MRD assessment in RUNX1-RUNX1T1¹ AML.