Development and Validation of a Time-Dependent Nomogram for Predicting Hematological Toxicity Risk During Linezolid...

Linezolid is essential for drug-resistant tuberculosis (DR-TB) treatment but causes frequent hematological toxicity. We developed a time-dependent nomogram to predict this risk.

A prospective cohort of 201 patients with DR-TB receiving linezolid (600 mg/day) was enrolled. Blood trough concentration (C_min) and clinical variables were measured. Multivariable Cox regression identified predictors, with a nomogram constructed to estimate toxicity probability at 1, 3, and 6 months. Model performance was assessed via calibration curves, C-index, and time-dependent area under the curve (AUC).

Ninety-six patients (47.8%) developed hematological adverse events (anemia: 26.4%, leukopenia: 14.4%, thrombocytopenia: 7.0%). Five predictors were significant: C_min > 2.08 mg/L [Hazard Ratio (HR) = 2.87, p < 0.001]; lower baseline white blood cells (HR = 0.84, p = 0.003), hemoglobin (HR = 0.99, p = 0.033), and creatinine clearance rate (HR = 0.99, p = 0.001); and initial treatment (HR = 0.56 vs. retreatment, p = 0.011). The nomogram showed good discrimination (C-index = 0.73) and calibration. Time-dependent AUCs were 0.74 (1-month), 0.79 (3-month), and 0.80 (6-month). Internal validation via bootstrapping (1000×) confirmed robustness.

This nomogram, integrating C_min with baseline clinical factors, enables early identification of patients with DR-TB at high risk for hematotoxicity and could guide pre-emptive interventions. However, external validation is required to confirm its generalizability before widespread clinical implementation.