Development and Validation of a Prediction Model for Severe Pre-Engraftment Syndrome During the Treatment of Unrelated Umbilical Cord Blood Transplantation in Pediatric Patients.

Abstract

Background: Pre-engraftment syndrome (PES) is a common immune response during the early stages of umbilical cord blood transplantation (UCBT), but the severity classification of PES remains uncertain.

Objectives: To develop and validate a predictive model for PES severity in pediatric patients receiving UCBT.

Study design: This retrospective study (2017-2025) included 123 pediatric patients (training cohort) and 41 external validation cases. Uni- and multivariable analysis was conducted to assess the potential parameters affecting PES severity. Based on the multivariable Cox model, the optimal model's performance was illustrated using a nomogram and evaluated through discrimination and calibration.

Results: Infused CD34⁺ counts (hazard ratio [HR]: 1.249, 95% confidence interval [CI]: 1.037-1.503, p < 0.05), donor chimerism on day 7 (HR: 1.025, 95% CI: 1.010-1.040, p < 0.05), and serum IL-6 level on symptoms onset (HR: 1.101, 95% CI: 1.000-1.123, p < 0.05) were identified as independent risk factors. The predictive performance of this nomogram model was evaluated by C-index and AUC, with C-index of 0.754 (95% CI: 0.693-0.815) and 9-day and 14-day AUC of 0.757 (95% CI: 0.655-0.859) and 0.856 (95% CI: 0.699-0.981), respectively. High-risk patients (score ≥104.9) had higher 9-day severe PES incidence (65.4% vs. 11.4%, p < 0.05) and Grade II-IV/III-IV aGVHD rates (84.2%/59.9% vs. 48.2%/28.2%, p < 0.05). External validation in an independent cohort (n = 41) displayed a C-index of 0.821 (95% CI: 0.689-0.953) and 14-day AUC of 0.933 (95% CI: 0.873-0.993).

Conclusion: This predictive model could predict the severity of PES in pediatric patients undergoing UCBT, thereby promoting preemptive treatment.