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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-10-3064. This Article Full Text (PDF) All Versions of this Article: 2002-10-3064v1 101/9/3398    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sievers, E. L Articles by Loken, M. R Search for Related Content PubMed PubMed Citation Articles by Sievers, E. L Articles by Loken, M. R Social Bookmarking                   What's this? Submitted October 10, 2002 Accepted December 20, 2002 Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children's Cancer Group study of 252 acute myeloid leukemia patients Eric L Sievers*, Beverly J Lange, Todd A Alonzo, Robert B Gerbing, Irwin D Bernstein, Franklin O Smith, Robert J Arceci, William G Woods, and Michael R Loken Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Department of Pediatrics, Seattle, WA, USA Hematologics, Inc, Seattle, WA, USA Division of Oncology, Childrens Hospital of Philadelphia, Philadelphia, PA, USA Department of Preventative Medicine, University of Southern California, Los Angeles, CA, USA Division of Hematology and Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA Division of Pediatric Oncology and the Department of Oncology and Pediatrics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA Pediatric Hematology-Oncology-BMT, Children's Healthcare of Atlanta/Emory University, Atlanta, GA, USA Childrens Oncology Group, Arcadia, CA, USA * Corresponding author; email: esievers{at}fhcrc.org. Approximately 40% of children with acute myeloid leukemia (AML) who respond to initial therapy subsequently relapse. Multidimensional flow cytometry employing a standardized panel of monoclonal antibodies enables the detection of small numbers of occult leukemic cells that persist during therapy using technology adaptable by most clinical laboratories. We performed a prospective, blinded evaluation of bone marrow specimens obtained from 252 pediatric patients with de novo AML to determine whether detection of occult leukemia defined as 0.5% blasts with aberrant surface antigen expression as determined by flow cytometry was predictive of subsequent relapse. Occult leukemia was detected in 41 (16 %) of the 252 patients who responded to initial induction therapy. In time dependent multivariate analyses that controlled for allogeneic marrow transplantation, variable intervals between sample submission, age, sex, white blood cell count at diagnosis, presence of splenomegaly or hepatomegaly, and presence of >15% blasts in the marrow after the first course of induction, patients harboring occult leukemia were 4.8 times more likely to relapse (95% CI = 2.8 to 8.4, p<0.0001) and 3.1 times more likely to die (95% CI; 1.9 to 5.1, p<0.0001) than those lacking leukemia detectable by flow cytometry. In this analysis, flow cytometric evidence of leukemia after the initiation of therapy emerged as the most powerful independent prognostic factor associated with poor outcome. Amongst patients in whom a marrow sample was available for analysis at the end of consolidation therapy, overall survival at 3 years was 41% vs. 69% for patients with and without occult leukemia, respectively (P=0.0058). 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