Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis
Sarah A. Buckley,
Brent L. Wood,
Megan Othus,
Christopher S. Hourigan,
Celalettin Ustun,
Michael A. Linden,
Todd E. DeFor,
Michele Malagola,
Chloe Anthias,
Veronika Valkova,
Christopher G. Kanakry,
Bernd Gruhn,
Francesco Buccisano,
Beth Devine,
Roland B. Walter
Affiliations
Sarah A. Buckley
Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA, USA
Brent L. Wood
Division of Hematopathology, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
Megan Othus
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Christopher S. Hourigan
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Celalettin Ustun
Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
Michael A. Linden
Division of Hematopathology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Todd E. DeFor
Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
Michele Malagola
Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, A.O. Spedali Civili, Italy
Chloe Anthias
Anthony Nolan Research Institute, London, UK;Royal Marsden Hospital, London, UK
Veronika Valkova
Institute of Haematology and Blood Transfusion, Prague, Czech Republic
Christopher G. Kanakry
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Bernd Gruhn
Department of Pediatrics, Jena University Hospital, Germany
Francesco Buccisano
Department of Hematology, Fondazione Policlinico Tor Vergata, Rome, Italy
Beth Devine
Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, WA, USA;Department of Health Services, University of Washington, Seattle, WA, USA;Department of Biomedical Informatics, University of Washington, Seattle, WA, USA
Roland B. Walter
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA;Department of Epidemiology, University of Washington, Seattle, WA, USA
Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 [1.90–4.00]), overall survival (hazard ratio=2.36 [1.73–3.22]), and cumulative incidence of relapse (hazard ratio=3.65 [2.53–5.27]), but not non-relapse mortality (hazard ratio=1.12 [0.81–1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I2=75.1% vs.
