Improved FLT3 Internal Tandem Duplication PCR Assay Predicts Outcome after Allogeneic Transplant for Acute Myeloid Leukemia
Journal
Biology of Blood and Marrow Transplantation
Journal Volume
20
Journal Issue
12
Pages
1989-1995
Date Issued
2014
Author(s)
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. ? 2014 American Society for Blood and Marrow Transplantation.
Subjects
Acute myeloid leukemia (AML); Bone marrow transplant; FLT3; Internal tandem duplication(ITD); Minimal residual disease(MRD); Tandem duplication PCR(TD-PCR)
SDGs
Other Subjects
busulfan; CD135 antigen; cyclophosphamide; fludarabine; CD135 antigen; FLT3 protein, human; acute granulocytic leukemia; adult; allotransplantation; Article; cancer patient; cancer recurrence; cancer regression; cancer survival; clinical article; controlled study; female; gene duplication; gene mutation; genetic parameters; human; internal tandem duplication; male; myeloablative conditioning; polymerase chain reaction; prediction; recurrence free survival; treatment outcome; allograft; blood; gene expression regulation; genetics; Leukemia, Myeloid, Acute; middle aged; minimal residual disease; nucleotide sequence; polymerase chain reaction; predictive value; recurrent disease; stem cell transplantation; Adult; Allografts; DNA Mutational Analysis; Female; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutagenesis, Insertional; Neoplasm, Residual; Polymerase Chain Reaction; Predictive Value of Tests; Recurrence; Stem Cell Transplantation
Publisher
Elsevier Inc.
Type
journal article