title: Improved FLT3 internal tandem duplication PCR assay predicts outcome after allogeneic transplant for acute myeloid leukemia.
abstract: Patients with acute myeloid leukemia (AML) who harbor internal tandem duplication (ITD) mutations of the FMS-like tyrosine kinase 3 (FLT3) gene carry a poor prognosis. Although allogeneic transplantation may improve outcomes, relapse occurs frequently. The FLT3/ITD mutation has been deemed an unsuitable minimal residual disease (MRD) marker because it is unstable and because the standard assay for the mutation is relatively insensitive. The FLT3 mutation is undetectable by PCR at pre- or post-transplant time points in many FLT3/ITD AML patients who subsequently relapse after transplant. We report the application of a new technique, tandem duplication PCR (TD-PCR), for detecting MRD in FLT3/ITD AML patients. Between October 2004 and January 2012, 54 FLT3/ITD AML patients in remission underwent transplantation at our institution. Of 37 patients with available day 60 marrow samples, 28 (76%) were assessable for MRD detection. In seven of 28 patients (25%), the FLT3/ITD mutation was detectable by TD-PCR but not by standard PCR on day 60. Six of 7 patients (86%) with MRD by TD-PCR have relapsed to date compared with only 2 of 21 patients (10%) who were negative for MRD (P = .0003). The ability to detect MRD by this sensitive technique may provide an opportunity for early clinical intervention.
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grunwald
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Tseng
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ming-Tseh
authors.initials: MT
authors.lastname: Lin
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Pratz
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Levis
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. Electronic address: cgocke1@jhmi.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gocke
mesh_terms: D000328:Adult; D064591:Allografts; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012008:Recurrence; D033581:Stem Cell Transplantation; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia (AML); Bone marrow transplant; FLT3; Internal tandem duplication (ITD); Minimal residual disease (MRD); Tandem duplication PCR (TD-PCR)