Cellular Immunity Profile in B-Cell Non-Hodgkin Lymphoma Patients Receiving Rituximab-Based Chemotherapy

Rituximab-based chemotherapy improves outcomes in B-cell non-Hodgkin lymphoma (NHL), but may exacerbate treatment-related immunosuppression, increasing the risk of opportunistic infections. Infection prophylaxis is not routinely implemented in Indonesia. This study aimed to characterize cellular immunity changes associated with rituximab-based chemotherapy and compare them with non-rituximab chemotherapy.

This prospective cohort study was conducted at two tertiary hospitals between March 2024 and October 2025. Adult patients with biopsy-confirmed B-cell NHL were enrolled in the rituximab-containing or non-rituximab chemotherapy groups. The absolute lymphocyte count, CD4 and CD8 counts, and their relative percentages were measured before treatment and after the third chemotherapy cycle. Comparative and intragroup analyses were performed using the appropriate statistical tests.

From 115 recruited patients, 71 completed the post-cycle-3 assessment (58 receiving rituximab-based chemotherapy, 13 receiving chemotherapy without rituximab). Baseline immune parameters were comparable between the groups. After chemotherapy, the case group demonstrated significantly lower absolute CD4 count (median 231.5 vs 423.0/µL; p=0.014), higher relative CD8 percentage (47.1% vs 34.9%; p=0.004), and a lower CD4/CD8 ratio (0.7 vs 0.9; p=0.014) compared with controls. Intragroup analysis showed significant reductions in absolute lymphocyte, CD4, and CD8 counts in the rituximab group, whereas the control group demonstrated decreases only in lymphocyte and CD8 counts, with CD4 counts largely preserved.

Rituximab-based chemotherapy was associated with greater suppression of cellular immunity, particularly CD4 depletion and CD4/CD8 ratio reduction, than chemotherapy alone. These findings support routine immune monitoring and provide immunological evidence that may help guide future prophylaxis strategies in rituximab-treated NHL patients, especially in settings with variable prophylaxis practices.