Fat-free mass and chemotherapy-related toxicity in patients with lymphoma: a prospective longitudinal cohort study

Background: Body surface area (BSA)-based chemotherapy dosing does not account for individual differences in body composition. Fat-free mass (FFM) has been proposed as a potential determinant of chemotherapy tolerance, although evidence remains limited and inconsistent, particularly in lymphoma patients. Methods: This prospective observational cohort study included 53 patients with malignant lymphoma receiving myelosuppressive chemotherapy. Patients were followed for up to seven treatment cycles. At each cycle, body composition was assessed using bioelectrical impedance analysis, and chemotherapy-induced side effects (CIS), physical activity, and quality of life were recorded using structured questionnaires. Dose-limiting toxicity (DLT) was defined as grade ≥ 3 toxicity, or treatment delay or dose reduction attributed to toxicity. The ratio of BSA to FFM (BSA/FFM) was used as a surrogate measure of relative chemotherapy dose per unit of lean body mass. Associations between body composition parameters, CIS, and DLT were explored across treatment cycles. Results: No significant overall changes in body weight, FFM, or fat mass were observed during treatment, although relative loss of FFM exceeded total weight loss. Patients experiencing DLT had a higher BSA/FFM ratio in selected treatment cycles (cycles 3, 5, and 6; p = 0.02–0.05) and demonstrated a greater decline in physical activity (p = 0.04). Correlations between body composition and CIS were inconsistent and primarily observed in subgroups and later treatment cycles. Receiver operating characteristic analyses suggested potential BSA/FFM thresholds associated with DLT; however, these findings were not stable across cycles. Conclusions: In this exploratory cohort of lymphoma patients, higher BSA/FFM ratios were associated with DLT in selected treatment cycles, but no consistent relationship between FFM-based dosing and chemotherapy-induced side effects was observed. These findings do not support replacing BSA-based dosing with FFM-based approaches. Further studies with larger, more homogeneous populations and pharmacokinetic data are warranted.