Early Lymphocyte Dynamics and Subsequent Cancer Therapy–Related Cardiac Dysfunction in Patients Receiving Anthracycline Therapy
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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.
Clinical Perspective
What Is New?
A less pronounced early decline in lymphocyte percentage during the first 30 days after anthracycline initiation was associated with higher odds of subsequent cancer therapy–related cardiac dysfunction (CTRCD).
What Are the Clinical Implications?
Early lymphocyte dynamics may provide modest incremental information beyond clinical characteristics, but prospective validation is needed before clinical application.
Graphic Abstract. Early Lymphocyte Response and Subsequent CTRCD After Anthracycline Therapy.
Among 362 adults with a recorded inpatient anthracycline order in MIMIC-IV, the primary exposure was the relative change in lymphocyte percentage from baseline to the nadir during days 0–30. CTRCD was defined as an LVEF decline of at least 10 percentage points to below 53%, assessed during days 31–365. A less pronounced early decline in lymphocyte percentage was associated with higher odds of subsequent CTRCD (overall association P = 0.031; OR, 1.96; 95% CI, 1.12–3.42, comparing the 90th with the 50th percentile). Adding lymphocyte change to the clinical model, which included baseline hemoglobin and immature granulocyte percentage, increased the optimism-corrected AUC from 0.644 to 0.658.
