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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-10-3064.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3398-3406
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Immunophenotypic evidence of leukemia after induction therapy
predicts relapse: results from a prospective Children's Cancer Group
study of 252 patients with acute myeloid leukemia
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
From the Clinical Research Division, Fred Hutchinson
Cancer Research Center, Seattle, WA; the Department of Pediatrics,
University of Washington, Seattle, WA; Hematologics, Inc, Seattle, WA;
the Division of Oncology, Children's Hospital of Philadelphia, PA; the
Department of Preventative Medicine, University of Southern California,
Los Angeles; the Division of Hematology and Oncology, Cincinnati
Children's Hospital Medical Center, University of Cincinnati College
of Medicine, OH; the Division of Pediatric Oncology and the Department
of Oncology and Pediatrics, Sidney Kimmel Comprehensive Cancer Center
at Johns Hopkins, Baltimore, MD; Pediatric Hematology-Oncology-BMT,
Children's Healthcare of Atlanta/Emory University, Atlanta, GA; and
the Children's Oncology Group, Arcadia, CA.
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 more than
or equal to 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 more than 15% blasts in the marrow after the first course
of induction, patients harboring occult leukemia were 4.8 times more
likely to relapse (95% confidence interval [CI] = 2.8 to 8.4, P < .0001) and 3.1 times more likely to die (95% CI;
1.9 to 5.1, P < .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. Among patients in whom a marrow sample was available for
analysis at the end of consolidation therapy, overall survival at 3 years was 41% versus 69% for patients with and without occult leukemia, respectively (P = .0058).

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