IL-8 and sCD40L predict platelet refractoriness and survival of pediatric patients with solid tumors receiving chemotherapy.

OBJECTIVE

To assess inflammation, endothelial damage, and platelet activation during platelet transfusion refractoriness (PTR) in pediatric patients with solid tumors.

METHODS

A cohort of 36 PTR and 38 Non-PTR pediatric patients with solid tumor was enrolled. Patients received standard chemotherapy and platelet transfusion according to guidelines. Levels of inflammatory mediators (IL-1β and IL-8, etc.), endothelial damage marker (vWF), and platelet activation markers (sP-selectin, sCD40L and RANTES) in pre-transfusion plasma were quantified by flow cytometry and ELISA. Associations with PTR, bleeding events, and progression-free survival (PFS) were analyzed by multivariable regression and Cox models.

RESULTS

The PTR group showed significantly high levels of sP-selectin (14.1 vs. 6.0 ng/mL), sCD40L (293.4 vs. 206.2 pg/mL), vWF (231.7 vs. 162.3 µg/mL), IL-1β (67.4 vs. 38.9 pg/mL), and IL-8 (61.0 vs. 29.2 pg/mL). Multivariable analysis identified vWF (OR = 1.006), IL-1β (OR = 1.013), and IL-8 (OR = 1.021) as independent predictors of PTR. Predictive model combining these three markers with malignancy risk stratification significantly improved the predictive ability of PTR compared to clinical Model alone (AUC: 0.846 vs. 0.692, P = 0.003). Clinically, PTR patients had delayed platelet recovery (10.2 vs.7.3 days), higher bleeding (36.1% vs. 13.2%), and reduced 500-day PFS (41.5% vs. 55.2%). Elevated sP-selectin (≥ 10.1 ng/mL) and sCD40L (≥ 234.5 pg/mL) predicted bleeding. After adjustment for malignancy risk stratification, high sCD40L (HR = 3.853, 95% CI: 1.097–13.525) remained independently associated with lower PFS, whereas IL ‑ 8 showed a trend but was not statistically significant.

CONCLUSION

Elevated IL-8 and sCD40L are novel predictors of PTR and survival prognostic in pediatric patients with solid tumors undergoing chemotherapy. IL-1β, IL-8 and vWF are identified as independent risk factors for PTR. sP-selectin and sCD40L are associated with increased bleeding risk, and high sCD40L is independent predictors of lower 500-day PFS.