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On 16 June 2019, at the 24th European Hematology Association Congress in Amsterdam, Frank G. Rücker and Richard Dillon presented evidence for minimal residual disease (MRD) monitoring in AML from the AML study group (AMLSG)1 and the UK National Cancer Research Institute (NCRI) AML17 study.2
The study sought to correlate pre-transplant molecular MRD status with outcome in patients with NPM1 mutant AML to identify clinically relevant MRD thresholds, assess interaction with standard prognostic factors and observe the effect of transplant type. They analysed pre-transplant blood and bone marrow samples using reverse-transcription polymerase chain reaction (RT-qPCR) and compared MRD to overall survival (OS). They also examined the effect of FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD), donor source, conditioning regimen and T-cell depletion on outcome.
The AMLSG study also aimed to correlate molecular MRD status with outcome. They studied patients with AML featuring recurrent genetic abnormalities (RUNX1-RUNX1T1 gene fusion), quantifying RUNX1-RUNX1T1 transcription levels (TL) in bone marrow (BM) and PB at various treatment stages.
The results of these studies suggest that a refined practical guideline for MRD assessment in AML is needed. The AM17 study demonstrated that in patients with NPM1 mutant AML, MRD negativity prior to transplant predicted outcome, with above 200 copies/105 of Abelson murine leukemia viral oncogene homolog gene (ABL) in the PB or 1000 copies in the BM indicative of an adverse outcome. Below this level FLT3-ITD and post-induction PB status were strongly associated with poor outcome. T-cell depletion was also associated with adverse outcome in patients who were MRD positive.
In RUNX1-RUNX1T1-positive AML MRD monitoring allows for the discrimination of pts at high and low risk of relapse. Therefore, MRD in BM and PB should be analyzed after each treatment cycle and in follow-up according to MRD status as below:
This study also noted very short latency from molecular to morphologic relapse, indicating that MRD assessment at shorter intervals during the first year post-treatment is indispensable.
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