title: A multigene array for measurable residual disease detection in AML patients undergoing SCT.
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.
authors: Myeloid Malignancies Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: M
authors: M
authors: Goswami
authors: Myeloid Malignancies Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: K S
authors: KS
authors: McGowan
authors: Stem Cell Allogenic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: K
authors: K
authors: Lu
authors: Stem Cell Allogenic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: N
authors: N
authors: Jain
authors: 1] Department of Physics, University of Maryland, College Park, MD, USA [2] School of Medicine, University of Maryland, Baltimore, MD, USA.
authors: J
authors: J
authors: Candia
authors: Stem Cell Allogenic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: N F
authors: NF
authors: Hensel
authors: Myeloid Malignancies Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: J
authors: J
authors: Tang
authors: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors: K R
authors: KR
authors: Calvo
authors: Stem Cell Allogenic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: M
authors: M
authors: Battiwalla
authors: Stem Cell Allogenic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: A J
authors: AJ
authors: Barrett
authors: Myeloid Malignancies Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: C S
authors: CS
authors: Hourigan
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000628:therapy*; D008297:Male; D018365:Neoplasm, Residual / Q000097:blood; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D033581:Stem Cell Transplantation