Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party

Abstract

Measurable residual disease (MRD; previously termed minimal residual disease) is an independent, postdiagnosis, prognostic indicator in acute myeloid leukemia (AML) that is important for risk stratification and treatment planning, in conjunction with other well-established clinical, cytogenetic, and molecular data assessed at diagnosis. MRD can be evaluated using a variety of multiparameter flow cytometry and molecular protocols, but, to date, these approaches have not been qualitatively or quantitatively standardized, making their use in clinical practice challenging. The objective of this work was to identify key clinical and scientific issues in the measurement and application of MRD in AML, to achieve consensus on these issues, and to provide guidelines for the current and future use of MRD in clinical practice. The work was accomplished over 2 years, during 4 meetings by a specially designated MRD Working Party of the European LeukemiaNet. The group included 24 faculty with expertise in AML hematopathology, molecular diagnostics, clinical trials, and clinical medicine, from 19 institutions in Europe and the United States.

Pattern associated leukemia immunophenotypes and measurable disease detection in acute myeloid leukemia or myelodysplastic syndrome with mutated NPM1

“…This approach can be considered as an example of, "LAIP-based difference-from-normal" recommended by the European LeukemiaNet MRD Working Party (18). This approach can be considered as an example of, "LAIP-based difference-from-normal" recommended by the European LeukemiaNet MRD Working Party (18).…”

Measurable residual disease monitoring using Wilms tumor gene 1 expression in childhood acute myeloid leukemia based on child‐specific reference values

“…Previous studies include mixed study cohorts of both children and adults, or primarily investigate WT1 expression at diagnosis, during treatment, or prior to hematopoietic stem cell transplantation (HSCT) . A recent consensus document from the MRD working group within the European LeukemiaNet (ELN) recommends peripheral blood (PB) for WT1 monitoring in patients without established MRD targets . This recommendation is based on reports on sequential WT1 measurements in PB during follow‐up being able to predict imminent relapse in adults .…”

Current treatment strategies for measurable residual disease in patients with acute myeloid leukemia

“…2 Because expertise in such methods is variable, the statement recommended that patient samples be sent to experienced centers and that common commercial panels be developed when possible. 2 Because expertise in such methods is variable, the statement recommended that patient samples be sent to experienced centers and that common commercial panels be developed when possible.…”

“…2 Specific markers, such as those for NPM1, RUNX1-RUNX1T1, CBFB-MYH11, and PML-RARA, can be detected using quantitative PCR at a sensitivity of 10 -4 to 10 -6 . Because a pretreatment marker first must be identified, molecular MRD assessment is applicable only to approximately 40% of patients.…”