Clonal Hematopoiesis Complicates MRD Assessment in Acute Myeloid Leukemia
This Blood review examines how persistent clonal hematopoiesis in treated AML patients confounds molecular MRD detection, since many mutations detected after treatment reflect ancestral clones, myelodysplastic syndrome, or newly emerging clones rather than residual leukemia. The authors propose standardized terminology for different types of post-treatment hematopoietic clones and review clinical data on their significance. Understanding these distinctions is critical for laboratories performing molecular MRD testing to avoid misclassifying clonal hematopoiesis as residual disease.
The original study
Clonal hematopoiesis and measurable residual disease assessment in acute myeloid leukemia.
- Authors
- Hasserjian RP, Steensma DP, Graubert TA, Ebert BL
- Journal
- Blood
- Type
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
- PMID
- 32232484
Original abstract
Current objectives regarding treatment of acute myeloid leukemia (AML) include achieving complete remission (CR) by clinicopathological criteria followed by interrogation for the presence of minimal/measurable residual disease (MRD) by molecular genetic and/or flow cytometric techniques. Although advances in molecular genetic technologies have enabled highly sensitive detection of AML-associated mutations and translocations, determination of MRD is complicated by the fact that many treated patients have persistent clonal hematopoiesis (CH) that may not reflect residual AML. CH detected in AML patients in CR includes true residual or early recurrent AML, myelodysplastic syndrome or CH that is ancestral to the AML, and independent or newly emerging clones of uncertain leukemogenic potential. Although the presence of AML-related mutations has been shown to be a harbinger of relapse in multiple studies, the significance of other types of CH is less well understood. In patients who undergo allogeneic hematopoietic cell transplantation (HCT), post-HCT clones can be donor-derived and in some cases engender a new myeloid neoplasm that is clonally unrelated to the recipient's original AML. In this article, we discuss the spectrum of CH that can be detected in treated AML patients, propose terminology to standardize nomenclature in this setting, and review clinical data and areas of uncertainty among the various types of posttreatment hematopoietic clones.