Risk- and Response-Adapted Treatment in Pediatric Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive and often fatal disorder. This study aimed to evaluate the stratification and treatment of pediatric Epstein-Barr virus-associated HLH (EBV-HLH) based on cytokine levels and clinical condition.

Pediatric patients newly diagnosed with EBV-HLH (n = 108) were risk stratified by cytokine and clinical criteria. Six were excluded for protocol violations.

Among the 102 evaluable patients, 61 and 41 were classified as low and high risk and initially received dexamethasone treatment and HLH-94/04 regimens, respectively. Notably, 32.4% of children (33/102) were cured by dexamethasone monotherapy. The 12-month overall survival (OS) for the entire cohort was 86.3% (95% CI, 79.6%-93.0%), with 91.8% (95% CI, 84.9%-98.7%) and 78.0% (95% CI, 65.3%-90.7%) for patients at low and high risk, respectively (P = .037). Patients at low risk whose treatment shifted from dexamethasone to the HLH-94/04 regimen presented similar 12-month OS as those initially treated with the HLH-94/04 regimen (82.1% [95% CI, 68.0%-96.2%] vs 78.0% [95% CI, 65.3%-90.7%]; P = .589). In multivariate Cox regression model, risk group and response to initial treatment at 48-72 hours thereafter were associated with OS.

A cytokine- and clinical-based risk stratification system, combined with dynamic response assessment, enables tailored treatment for pediatric patients with EBV-HLH.