Clinical Impact of Measurable Residual Disease in Acute Myeloid Leukemia

Abstract

Measurable residual disease (MRD) has emerged as a primary marker of risk severity and prognosis in acute myeloid leukemia (AML). There is, however, ongoing debate about MRD-based surveillance and treatment. A literature review was performed using the PubMed database with the keywords MRD or residual disease in recently published journals. Identified articles describe the prognostic value of pre-transplant MRD and suggest optimal timing and techniques to quantify MRD. Several studies address the implications of MRD on treatment selection and hematopoietic stem cell transplant, including patient candidacy, conditioning regimen, and transplant type. More prospective, randomized studies are needed to guide the application of MRD in the treatment of AML, particularly in transplant.

Keywords: AML; MRD; acute myeloid leukemia; hematopoietic stem cell transplant; measurable residual disease.

Figure 1

MRD Monitoring in AML. Recommendations adapted from the 2021 European LeukemiaNet Guidelines [10], the National Comprehensive Cancer Network AML Guidelines version 1.2022 [11], and our clinical experience and emerging data on lower intensity regimens [38]. Tissues for MRD testing include peripheral blood (PB) and bone marrow (BM). MRD quantification techniques include multiparameter flow cytometry (MFC), next-generation sequencing (NGS), and quantitative polymerase chain reaction (qPCR). * Bone marrow studies can be obtained as clinically indicated in patients on continuation/maintenance therapy or after treatment completion.

Figure 2

Six scenarios of AML treatment based on European LeukemiaNet (ELN) risk category and measurable residual disease (MRD) status. ELN risk categories are noted in the first column [3]. MRD status is first established after achieving remission and up to two cycles of chemotherapy, as defined in the ELN consensus 2021 update [10]. As the most significant timepoint of MRD-negative state in relation to treatment administered remains unknown, we show MRD status after initial induction and/or consolidation chemotherapy. Abbreviations: measurable residual disease positive (MRD+); measurable residual disease negative (MRD-); treatment (tx); allogeneic hematopoietic stem cell transplant (allo-HSCT); autologous hematopoietic stem cell transplant (auto-HSCT).