Minimal Residual Disease Detection by Flow Cytometry in Adult T-Cell Leukemia/Lymphoma

Abstract

Little information exists regarding the detection of minimal residual disease (MRD) in adult T-cell leukemia/lymphoma (ATLL). We evaluated 75 peripheral blood samples from 17 ATLL cases using flow cytometry (FC); 50 of the samples were concurrently evaluated by polymerase chain reaction (PCR) for clonal T-cell receptor gamma chain (TRG) gene rearrangement and the presence of human T-cell lymphotropic virus-1 proviral sequences. Residual ATLL cells were identified using a multiparametric approach to identify aberrant T-cell immunophenotypes. Malignant T cells were CD4+, CD3 dim+, CD26-, CD25 bright, CD7+, and CD27+, with occasional dim expression of CD2 or CD5. FC exhibited a high sensitivity, detecting as few as 0.29% ATLL cells/WBC (4.9 cells/microL) in the peripheral blood. PCR for TRG gene rearrangement was slightly more sensitive, and FC and PCR complemented each other in detecting MRD. In 2 patients, there was complete remission; 4 patients had disease refractory to therapy, and 3 died; 11 others had persistent disease with variable numbers of ATLL cells in the peripheral blood. Higher levels of ATLL cells appeared to correlate with disease severity. FC detection of aberrant T cells permits sensitive and quantitative monitoring of MRD in ATLL.