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(−) 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.