Abstract
The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two cycles of consolidation (n = 421). The latter time point was proved as a superior indicator with independent prognostic significance for both relapse-free survival (RFS, HR = 3.635, 95% CI: 2.433–5.431, P <0.001) and overall survival (OS: HR = 3.511, 95% CI: 2.191–5.626, P <0.001). Furthermore, several representative molecular MRD markers were compared with the MFC MRD. Both approaches can establish prognostic value in patients with NPM1 mutations, and FLT3, C-KIT, or N-RAS mutations involved in kinase-related signaling pathways, while the combination of both techniques further refined the risk stratification. The detection of RUNX1–RUNX1T1 fusion transcripts achieved a considerable net reclassification improvement in predicting the prognosis. Conversely, for patients with biallelic CEBPA or DNMT3A mutations, only the MFC method was recommended due to the poor prognostic discriminability in tracking mutant transcripts. In conclusion, this study demonstrated that the MFC MRD after two consolidation cycles independently predicted clinical outcomes, and the integration of MFC and molecular MRD should depend on different types of AML-related genetic lesions.
Highlights
Acute myeloid leukemia (AML) is a group of hematological malignant disorders characterized by the high heterogeneity in clinical manifestation, genetic abnormalities, and prognosis [1]
Among the 833 acute myeloid leukemia (AML) patients, 639 (76.7%) achieved complete remission (CR) after induction chemotherapy, of whom 587 (91.9%) patients had specific LAIPs at diagnosis that were suitable for Measurable residual disease (MRD) monitoring by flow cytometry
There is mounting evidence that the identification of residual disease is of paramount importance in refining risk reclassification and informing therapeutic intervention for AML patients after the achievement of morphological remission [16, 22, 23]
Summary
Acute myeloid leukemia (AML) is a group of hematological malignant disorders characterized by the high heterogeneity in clinical manifestation, genetic abnormalities, and prognosis [1]. Via the treatment modalities as exemplified by cytotoxic drugs or molecular targeted therapies, a high complete remission (CR) rate could be achieved, a substantial proportion of AML patients. MFC and Gene MRD Detection in AML will relapse due to residual leukemic cells below the detection threshold of traditional morphologic methods. Measurable residual disease (MRD; named minimal residual disease) detected in AML patients with hematological complete remission after treatment has been suggested as a powerful prognostic indicator [4, 5]. MRD is reliably monitored using the two most common methods, multiparameter flow cytometry-based MRD (MFC MRD) and polymerase chain reaction (PCR)-based MRD (Gene MRD), quantifying MRD in AML by virtue of either immunophenotype or molecular abnormalities of leukemic cells. Until now, issues on when and how to apply the evaluation of MRD in daily clinical practice are still controversial
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