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Bone Marrow Transplant. 2015 May;50(5):642-51. doi: 10.1038/bmt.2014.326. Epub 2015 Feb 9.

A multigene array for measurable residual disease detection in AML patients undergoing SCT.

Author information

1
Myeloid Malignancies Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
2
Stem Cell Allogenic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
3
1] Department of Physics, University of Maryland, College Park, MD, USA [2] School of Medicine, University of Maryland, Baltimore, MD, USA.
4
Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.

Abstract

AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ-PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994-2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ-PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection.

PMID:
25665046
PMCID:
PMC4424111
DOI:
10.1038/bmt.2014.326
[Indexed for MEDLINE]
Free PMC Article

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