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.

Measurable residual disease monitoring by ddPCR in the early posttransplant period complements the traditional MFC method to predict relapse after HSCT in AML/MDS: a multicenter retrospective study

“…The selection of ddPCR for MRD monitoring is often driven by its ability to perform absolute quantification of nucleic acids, resulting in increased sensitivity and accuracy of detection with a lower limit of detection of 0.001% compared to MFC and NGS and without the requirement of a standard curve compared to qPCR [37,38]. Although NGS has the advantage of detecting complete mutations or fusion genes and monitoring clone evolution or the generation of new genes before and after transplantation, it is still challenging due to its time-consuming and overpriced drawbacks, while most relapsed patients have at least one molecular target in common with their initial diagnosis [26,27,39], indicating that a large number of allo-HSCT recipients have sufficient targets to trace MRD status by ddPCR after transplantation.…”

Measurable Residual Disease Detection in Acute Myeloid Leukemia: Current Challenges and Future Directions

“…The process involves the initial partition of the template of interest into different compartments, and the ultimate analysis relies on thousands of individual measurements. By allowing absolute quantification, dPCR is easier to standardize and also can offer greater sensitivity than qPCR, especially when quantifying diseases at extremely low levels [ 19 , 92 ]. Limitations of dPCR include high variability in detectability of targets according to sample material (PB vs. BM) and not all different types of each mutation can be covered.…”

Minimal residual disease monitoring in acute myeloid leukemia: Focus on MFC‐MRD and treatment guidance for elderly patients

“…Most facilities use bone marrow morphology, cytogenetics, immunophenotyping, and molecular studies to maximize AML diagnoses and MRD technique effectiveness, following NCCN, ELN, and American Society of Clinical Oncology (ASCO) criteria. 8 Factors like as sensitivity, applicability to different AML subtypes, cost, and technical skill determine the selection of a suitable MRD test. 5,9,10 The vast majority, exceeding 90%, of AML-diagnosed individuals exhibit aberrant markers identifiable through flow cytometry.…”

“…Polymerase chain reaction (PCR) MRD detection methods include quantitative PCR (qPCR) and digital droplet PCR (ddPCR). qPCR is a commonly used method, yet ddPCR is more efficient, sensitive, and consistent, without the need for a standardization curve or reference materials 8 . NPM1, Core Binding Factor (CBF)‐AML (using the fusion genes CBFB:MYH11 and RUNX1::RUNX1T1), and Acute Promyelocytic Leukemia (APL) (using the PML:RARA fusion gene) are three clinically relevant phenotypic detection approaches that PCR has created 13 .…”

“…6 MRD assessment in AML serves various purposes, including: (1) providing quantitative methods for evaluating the extent of remission, (2) enhancing the evaluation of relapse risk post-remission, (3) detecting early signs of relapse for timely intervention, (4) acting as a stand-in endpoint to speed up the approval and drug testing procedures. 7 There's currently no consensus on using MRD in treating healthy patients with intensive chemotherapy or frail patients with lowintensity chemotherapy for AML 8 . The questions revolve around when and how to perform MRD testing, its impact on treatment decisions, and whether PB monitoring can replace BM aspirations.…”