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Br J Haematol. 2020 Mar 16. doi: 10.1111/bjh.16560. [Epub ahead of print]

Measurable residual disease assessment by qPCR in peripheral blood is an informative tool for disease surveillance in childhood acute myeloid leukaemia.

Author information

1
Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
2
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
3
Haematology-Pathology Research Laboratory, Department of Haematology, Odense University Hospital, Odense, Denmark.
4
Department of Paediatrics III, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany.
5
Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway.
6
Laboratory of Molecular Haematology and Pathology, Turku University Central Hospital, Turku, Finland.
7
Department of Paediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
8
Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
9
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
10
Department of Paediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
11
Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
12
Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

Serial assessments of measurable (or minimal) residual disease (MRD) by qPCR may identify nascent relapse in children with acute myeloid leukaemia (AML) and enable pre-emptive therapy. We investigated the kinetics and prognostic impact of recurrent fusion transcripts (RUNX1-RUNX1T1, CBFB-MYH11, KMT2A-MLLT3 or KMT2A-ELL) in 774 post-induction samples from bone marrow (BM, 347) and peripheral blood (PB, 427) from 75 children with AML. BM MRD persistence during consolidation did not increase the risk of relapse, and MRD at therapy completion did not correlate to outcome (HR = 0·64/MRD log reduction (CI: 0·32-1·26), P = 0·19). In contrast, 8/8 patients with detectable MRD in PB after first consolidation relapsed. Persistence (n = 4) and shifting from negative to positive (n = 10) in PB during follow-up predicted relapse in 14/14 patients. All 253 PB samples collected during follow-up from 36 patients in continuous complete remission were MRD negative. In core-binding factor AML, persistent low-level MRD positivity in BM during follow-up was frequent but an increment to above 5 × 10-4 heralded subsequent haematological relapse in 12/12 patients. We demonstrate that MRD monitoring in PB after induction therapy is highly informative and propose an MRD increment above 5 × 10-4 in PB and BM as a definition of molecular relapse since it always leads to haematological relapse.

KEYWORDS:

acute myeloid leukaemia; fusion transcripts; measurable residual disease; paediatric haematology; relapse

PMID:
32175599
DOI:
10.1111/bjh.16560

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