Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping

Adult T-cell leukemia/lymphoma (ATL), a human T-lymphotropic virus type 1 (HTLV-1)-associated disease, has a highly variable clinical course and four subtypes with therapeutic and prognostic implications. However, there are overlapping features between ATL subtypes and between ATL and nonmalignant (non-ATL) HTLV-1 infection complicating diagnosis and prognostication. To further refine the diagnosis and prognosis of ATL, we characterized the immunophenotype of HTLV-1-infected cells in ATL and non-ATL. A retrospective study of peripheral blood samples from 10 HTLV-1-uninfected subjects (UI), 54 HTLV-1-infected patients with non-ATL, and 22 with ATL was performed using flow cytometry. All patients with ATL had CD4(+) CCR4(+) CD26(-) immunophenotype and the frequency of CD4(+) CCR4(+) CD26(-) T cells correlated highly significantly with the proviral load in non-ATL suggesting CD4(+) CCR4(+) CD26(-) as a marker of HTLV-1-infected cells. Further immunophenotyping of CD4(+) CCR4(+) CD26(-) T cells revealed that 95% patients with ATL had a CD7(-) (<= 30% CD7(+) cells), whereas 95% HTLV+ non-ATL had CD7(+) (>30% CD7(+) cells) immunophenotype. All patients with aggressive ATL had a CCR7(+) (>= 30%), whereas 92% with indolent ATL and 100% non-ATL had a CCR7(-) (<30%) immunophenotype. Patients with nonprogressing indolent ATL were CD127(+) but those with progressive lymphocytosis requiring systemic therapy had a CD127(-) (<= 30%) immunophenotype. In summary, HTLV-1-infected cells have a CD4(+) CCR4(+) CD26(-) immunophenotype. Within this population, CD7(-) phenotype suggests a diagnosis of ATL, CCR7(+) phenotype identifies aggressive ATL, while CCR7(-) CD127(-) phenotype identifies progressive indolent ATL.