Early Lymphocyte Dynamics and Subsequent Cancer Therapy-Related Cardiac Dysfunction in Patients Receiving Anthracycline Therapy

Background: Whether early treatment-related lymphocyte dynamics are associated with cancer therapy?related cardiac dysfunction (CTRCD) after anthracycline therapy is uncertain. This study sought to determine the association between early change in lymphocyte and subsequent CTRCD and to assess its incremental value beyond clinical characteristics. Methods: We retrospectively studied anthracycline-treated adults in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database with linked echocardiographic data (MIMIC-IV-Echo). The primary exposure was relative change in lymphocyte percentage from baseline to the 0?30-day nadir. CTRCD was defined as a left ventricular ejection fraction (LVEF) decline ?10 percentage points to <53%. Associations were modeled using multivariable logistic regression with restricted cubic splines. Incremental discrimination was assessed using optimism-corrected AUCs. Results: Among 362 patients in the analysis cohort, 58 (16.0%) developed CTRCD. Baseline lymphocyte measures were not associated with CTRCD. Early lymphocyte percentage change was associated with CTRCD (overall P=0.031). Compared with the median change (?73%), a less pronounced decline at the 90th percentile (?5%) was associated with higher odds of CTRCD (OR: 1.96; 95% CI: 1.12?3.42; P=0.018). The association remained consistent after sequential and hematologic adjustment. Added to a clinical model that included hemoglobin and immature granulocyte percentage, lymphocyte change increased the apparent AUC from 0.705 to 0.724 and the optimism-corrected AUC from 0.644 to 0.658 (P = 0.040). Conclusions: A less pronounced early decline in lymphocyte percentage after anthracycline initiation was associated with higher odds of subsequent CTRCD and provided modest incremental information beyond clinical characteristics.