High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361)

Multiparameter flow cytometry (MFC) has the potential to allow for sensitiv e and specific monitoring of residual disease (RD) in acute myeloid leukemi a (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 di agnosis and at first relapse using 9 panels of 3 monoclonal antibodies. Imm unophenotype changes occurred in 124 patients (91%); they consisted of gain s or losses of discrete leukemia cell populations resolved by MFC (42 patie nts) and gains or losses of antigens on leukemia cell populations present a t both time points (108 patients). Antigen expression defining unusual phen otypes 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 cel l 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 o f 8 3-antibody panels, which included antibodies to a total of 16 antigens, allowed identification of relapse AML cells in all cases. Thus, the immuno phenotype of AML cells is markedly unstable; nevertheless, despite this ins tability, MFC has the potential to identify RD in AML if multiple antibody panels are used at all time points.