TY - JOUR
T1 - MRD evaluation of AML in clinical practice
T2 - Are we there yet?
AU - Freeman, Sylvie D.
AU - Hourigan, Christopher S.
N1 - Funding Information:
Conflict-of-interest disclosure: C.S.H. has received laboratory research funding from Merck and Sellas. S.D.F. declares no competing financial interests.
Funding Information:
1Clinical Immunology Service, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; and 2Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Funding Information:
This research was supported in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute of the National Institutes of Health.
Publisher Copyright:
© 2019 American Society of Hematology. All rights reserved.
PY - 2019/12/6
Y1 - 2019/12/6
N2 - MRD technologies increase our ability to measure response in acute myeloid leukemia (AML) beyond the limitations of morphology. When applied in clinical trials, molecular and immunophenotypic MRD assays have improved prognostic precision, providing a strong rationale for their use to guide treatment, as well as to measure its effectiveness. Initiatives such as those from the European Leukemia Network now provide a collaborative knowledge-based framework for selection and implementation of MRD assays most appropriate for defined genetic subgroups. For patients with mutated-NPM1 AML, quantitative polymerase chain reaction (qPCR) monitoring of mutated-NPM1 transcripts postinduction and sequentially after treatment has emerged as a highly sensitive and specific tool to predict relapse and potential benefit from allogeneic transplant. Flow cytometric MRD after induction is prognostic across genetic risk groups and can identify those patients in the wild-typeNPM1 intermediate AML subgroup with a very high risk for relapse. In parallel with these data, advances in genetic profiling have extended understanding of the etiology and the complex dynamic clonal nature of AML, as well as created the opportunity for MRD monitoring using next-generation sequencing (NGS). NGS AML MRD detection can stratify outcomes and has potential utility in the peri-allogeneic transplant setting. However, there remain challenges inherent in the NGS approach of multiplex quantification of mutations to track AML MRD. Although further development of this methodology, together with orthogonal testing, will clarify its relevance for routine clinical use, particularly for patients lacking a qPCR genetic target, established validated MRD assays can already provide information to direct clinical practice.
AB - MRD technologies increase our ability to measure response in acute myeloid leukemia (AML) beyond the limitations of morphology. When applied in clinical trials, molecular and immunophenotypic MRD assays have improved prognostic precision, providing a strong rationale for their use to guide treatment, as well as to measure its effectiveness. Initiatives such as those from the European Leukemia Network now provide a collaborative knowledge-based framework for selection and implementation of MRD assays most appropriate for defined genetic subgroups. For patients with mutated-NPM1 AML, quantitative polymerase chain reaction (qPCR) monitoring of mutated-NPM1 transcripts postinduction and sequentially after treatment has emerged as a highly sensitive and specific tool to predict relapse and potential benefit from allogeneic transplant. Flow cytometric MRD after induction is prognostic across genetic risk groups and can identify those patients in the wild-typeNPM1 intermediate AML subgroup with a very high risk for relapse. In parallel with these data, advances in genetic profiling have extended understanding of the etiology and the complex dynamic clonal nature of AML, as well as created the opportunity for MRD monitoring using next-generation sequencing (NGS). NGS AML MRD detection can stratify outcomes and has potential utility in the peri-allogeneic transplant setting. However, there remain challenges inherent in the NGS approach of multiplex quantification of mutations to track AML MRD. Although further development of this methodology, together with orthogonal testing, will clarify its relevance for routine clinical use, particularly for patients lacking a qPCR genetic target, established validated MRD assays can already provide information to direct clinical practice.
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U2 - 10.1182/hematology.2019000060
DO - 10.1182/hematology.2019000060
M3 - Article
C2 - 31808906
AN - SCOPUS:85076243990
SN - 1520-4391
VL - 2019
SP - 557
EP - 569
JO - Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
JF - Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
IS - 1
ER -