Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)]

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t( 8; 21) and 27 an inv( 16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n = 17) of CR patients relapsed: seven with t( 8; 21) and 10 with inv( 16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% ( P = 0.002) at the end of treatment. The mean number of fusion transcript copies/ ABLx10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 ( P = 0.001) after induction, 56 vs 7.6 after intensification ( P = 0.0001) and 75 vs 3.3 ( P = 0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level 40.1% at the end of treatment than in patients with <= 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% ( P = 0.03), respectively. Likewise, using RQ-PCR, a cutoff level of 410 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR410 compared to 21% for patients with RQ-PCR levels p10 ( P = 0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.