Monitoring of minimal residual disease (MRD) by real-time quantitative reverse transcription PCR (RQ-RT-PCR) in childhood acute myeloid leukemia with AML1/ETO rearrangement

Abstract

The fusion transcript AML1/ETO corresponding to translocation t(8;21)(q22;q22) can be found in approximately 7-12% of childhood de novo AML. Despite the favorable prognosis, some of these patients relapse. Most of MRD studies so far were performed on adults treated not uniformly. Therefore, we analyzed the follow-up of 15 AML1/ETO-positive children using real-time quantitative reverse transcription PCR (RQ-RT-PCR), all enrolled in the multicenter therapy trial AML-BFM 98. AML1/ ETO copy numbers were normalized to the control gene ABL and the results were expressed in copy numbers AML1/ETO per 10 000 copies ABL. At diagnosis, a median of 10 789 copies AML1/ETO was found. A linear decrease to about 10 copies (2-4 log) could be seen in most of the children by the start of consolidation. In the majority of cases they remained positive at this low level during the ongoing therapy. Four children relapsed and two of them had a decrease of less than 2 log before starting consolidation. Three of the relapsed children showed, prior to relapse, an increase of the AML1/ETO fusion transcript at 6, 9, and 11 weeks, respectively. These results suggest that monitoring of minimal residual disease using RQ-RT-PCR could be helpful in detecting patients with a higher risk of relapse.

Long-term results in children with AML: NOPHO-AML Study Group – report of three consecutive trials

“…The protocol will prospectively evaluate the prognostic importance of in vitro drug resistance and MRD levels at different time points. [27][28][29] This may help us to identify new subgroups in AML, which may benefit from different therapeutic strategies.…”

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21)

“…24 However, recently, several studies strongly suggested that RQ-RT-PCR might be a more valuable technique to predict relapse in AML with core binding factor (CBF) rearrangement in general or in t(8;21) AML. 13,14,[25][26][27] In those studies, critical thresholds of MRD levels, which could distinguish between patients at risk of relapse and those in continuous CR, were identified. In the present study, no pretreatment characteristics were predictive of the outcome, possibly due to the relatively low number of patients.…”

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

“…3 A study in childhood AML of 15 patients also showed that RUNX1-RUNX1T1 increased transcript levels are predictive of relapse. 188 MLL fusion transcripts for MRD monitoring have also been analyzed in 19 patients with t(9;11)(q22;q23) AML. Eleven of these patients showed negative PCR for the MLL fusion transcripts, and this associated with a better outcome.…”