A plasma-based DNA test for quantification of disease burden in acute myeloid leukemia patients undergoing bone marrow transplantation
Abstract
Allogeneic hematopoietic cell transplantation is the only curative option for many patients with acute myeloid leukemia (AML). In the current study, we designed and implemented a personalized assay, called v96, incorporating up to 96 mutations in 30 AML patients undergoing transplantation. The assay was performed on DNA derived from cells isolated from the bone marrow as well as in cell-free plasma. All 30 (100%) of patients harbored molecular evidence of residual leukemia during remission that was detectable by the v96 assay, while only 6 (20%) had evidence of disease as assessed by conventional clinical assays. Furthermore, cell-free DNA from plasma proved to be more sensitive than DNA from cells of the bone marrow for identifying residual leukemia. The median number of mutants was 352-fold higher in plasma taken prior to transplantation for patients who relapsed compared to those who did not relapse. At 2 mo posttransplantation, 27 of the 30 patients still harbored detectable leukemia as assessed by the v96 assay. Twenty-two of these patients had a subsequent decrease in leukemic burden assessed by the v96 assay. In the majority of them (20 of 22 patients), the decrease occurred only after immunosuppression was discontinued, supporting a graft-versus-leukemia effect. These results document the feasibility of using a relatively large panel of carefully chosen mutations and a highly specific assay as noninvasive markers of therapeutic response in AML patients, minimizing the need for multiple bone marrow biopsies.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (23)
Yuxuan Wang
Jiajun Xie
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Sergiu Pasca
Division of Hematologic Malignancies, Johns Hopkins University School of Medicine
Maria Popoli
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Janine Ptak
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Lisa Dobbyn
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Natalie Silliman
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Suman Paul
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Richard J. Jones
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Mark J. Levis
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Samuel D. Curtis
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine
Christopher Douville
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Cynthia Shams
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Matthew Z. Guo
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Shirley Mo
Division of Hematologic Malignancies, Johns Hopkins University School of Medicine
Christopher D. Gocke
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Sami N. Malek
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan
Catherine M. Bollard
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Chetan Bettegowda
Kenneth W. Kinzler
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Bert Vogelstein
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Nickolas Papadopoulos
Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Lukasz P. Gondek
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine