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 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. (Blood. 2001;97:3574-3580)

Use of rituximab, the new FDA-approved antibody.

Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA) is the first monoclonal antibody approved by the US Food and Drug Administration for the treatment of cancer. It is a genetically engineered chimeric (murine-human) monoclonal antibody (mAb) directed against the CD20 antigen found on the surface of normal and malignant B cells. Multicenter studies have demonstrated its efficacy against relapsed low-grade and follicular non-Hodgkin's lymphoma (NHL). The mAb demonstrated tolerable side effects, primarily limited to fevers and chills associated with the first infusion. The currently recommended dosage is 375 mg/m2/infusion, given weekly for 4 weeks. Because of its human component, rituximab has low immunogenicity and should not significantly hinder future retreatment. Future studies will evaluate the antitumor activity of rituximab combined with various other chemotherapeutic or biologic agents in the treatment of B-cell lymphoma and other CD20-positive lymphoid neoplasms.