ABSTRACT Objectives Pediatric AML with KMT2A::MLLT10 accounts for 10%–15% of KMT2A ‐rearranged AML and is associated with poor prognosis. Lately, the assessment of measurable residual disease (MRD) by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) has become an important tool for disease management; however, in the pediatric setting, it lacks standardized protocols. Therefore, we investigated the prognostic relevance of MRD monitoring by RT‐qPCR during high‐dose polychemotherapy in pediatric patients with AML expressing KMT2A::MLLT10 . Methods Using RNA sequencing, we determined the fusion breakpoints and designed RT‐qPCR assays for MRD monitoring. Bone marrow samples collected from 41 patients, who were treated in the AML‐BFM or AIEOP study, were analyzed for MRD by RT‐qPCR. Results MRD positivity after the second treatment course resulted in a significantly worse probability of overall survival (pOS) compared to MRD negative patients (33.3% ± 19.2% vs. 80.6% ± 7.8%, p = 0.032). Moreover, the probability of event‐free survival (pEFS) (16.7% ± 15.2% vs. 76.9% ± 8.3%, p = 0.003) and cumulative incidence of relapse (CIR) (83.3% ± 40.8% vs. 19.2% ± 40.2%, p = 0.001) were significantly worse for patients in complete morphologic remission who remained MRD positive after the second treatment course. Conclusion Thus, MRD monitoring enables the identification of a subgroup of pediatric patients with AML carrying KMT2A::MLLT10 in complete morphologic remission with a dismal prognosis despite the current intensive therapy regimen. Trial Registration AML‐BFM study 2004: ClinicalTrials.gov Identifier: NCT00111345; AML‐BFM registry 2012 and AML‐BFM study 2012: EudraCT 2013‐000018‐39; AML‐BFM registry 2017: DRKS number: DRKS00013030
Steidel et al. (Wed,) studied this question.
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