Circulating low CD4⁺/CD8⁺ ratio is associated with poor prognosis in Waldenstrom macroglobulinemia patients

Waldenstrom macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with great heterogeneity, and the data of peripheral blood T-lymphocyte subsets in WM are limited. This study aimed to investigate the clinical correlation and distribution of circulating T-lymphocyte subsets in newly diagnosed WM patients. We retrospectively searched medical records for 86 newly diagnosed WM patients. Comparisons of the absolute CD3⁺ T-lymphocyte count (ACD3C), CD4⁺ T-lymphocyte count (ACD4C), CD8⁺ T-lymphocyte count (ACD8C), and CD4⁺/CD8⁺ T-lymphocyte ratio (CD4⁺/CD8⁺) as continuous parameters in different groups were calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Young patients (<65 years) had lower ACD8C levels and a higher CD4⁺/CD8⁺ ratio. And the lower level of β2-microglobulin (<3 mg/L) was associated with a higher CD4⁺/CD8⁺ ratio. With a median follow-up of 25 months, the univariate survival analysis showed that CD4⁺/CD8⁺ ratio inversion (CD4⁺/CD8⁺<1.5) was associated with shorter OS and PFS, and multivariate analysis confirmed that inverted CD4⁺/CD8⁺ ratio could be an independent adverse prognostic factor for OS and PFS. Additionally, initial treatment with rituximab or bortezomib significantly improved the PFS and OS of CD4⁺/CD8⁺ inversion patients but did not affect normal CD4⁺/CD8⁺ patients. We show that low circulating CD4⁺/CD8⁺ ratio at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy which included rituximab or bortezomib significantly improved PFS and OS for patients with CD4⁺/CD8⁺ ratio less than 1.5.