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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3574-3580
NEOPLASIA
High frequency of immunophenotype changes in acute myeloid
leukemia at relapse: implications for residual disease
detection (Cancer and Leukemia Group B Study 8361)
Maria R. Baer,
Carleton C. Stewart,
Richard K. Dodge,
Gail Leget,
Norbert Sulé,
Krzysztof Mrózek,
Charles A. Schiffer,
Bayard L. Powell,
Jonathan E. Kolitz,
Joseph O. Moore,
Richard M. Stone,
Frederick R. Davey,
Andrew J. Carroll,
Richard A. Larson, and
Clara D. Bloomfield
From the Roswell Park Cancer Institute, Buffalo, New
York; CALGB Statistical Center, Durham, North Carolina; Southeastern
Cancer Center, Lumberton, North Carolina; The Ohio State University
Medical Center, Columbus, Ohio; Wayne State University School of
Medicine, Detroit, Michigan; Wake Forest University School of Medicine,
Winston-Salem, North Carolina; North Shore University Hospital,
Manhasset, New York; Duke University Medical Center, Durham,
North Carolina; Dana-Farber Cancer Institute, Boston,
Massachusetts; State University of New York Upstate Medical
University, Syracuse, New York; University of Alabama at Birmingham;
University of Chicago Medical Center, Chicago, Illinois.
Multiparameter flow cytometry (MFC) has the potential to allow for
sensitive and specific monitoring of residual disease (RD) in acute
myeloid leukemia (AML). The use of MFC for RD monitoring assumes that
AML cells identified by their immunophenotype at diagnosis can be
detected during remission and at relapse. AML cells from 136 patients
were immunophenotyped by MFC at diagnosis and at first relapse using 9 panels of 3 monoclonal antibodies. Immunophenotype changes
occurred in 124 patients (91%); they consisted of gains or losses of
discrete leukemia cell populations resolved by MFC (42 patients) and
gains or losses of antigens on leukemia cell populations present at
both time points (108 patients). Antigen expression defining unusual
phenotypes changed frequently: CD13, CD33, and CD34, absent at
diagnosis in 3, 33, and 47 cases, respectively, were gained at relapse
in 2 (67%), 15 (45%), and 17 (36%); CD56, CD19, and CD14, present at
diagnosis in 5, 16, and 20 cases, were lost at relapse in 2 (40%), 6 (38%), and 8 (40%). Leukemia cell gates created in pretreatment
samples using each 3-antibody panel allowed identification of relapse
AML cells in only 68% to 91% of cases, but use of 8 3-antibody
panels, which included antibodies to a total of 16 antigens, allowed
identification of relapse AML cells in all cases. Thus, the
immunophenotype of AML cells is markedly unstable; nevertheless,
despite this instability, MFC has the potential to identify RD in
AML if multiple antibody panels are used at all time points.
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