J Infect Dis. 2025 Oct 31:jiaf556. doi: 10.1093/infdis/jiaf556. Online ahead of print.
ABSTRACT
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive and often fatal disorder that requires timely and effective intervention to improve patient outcomes. However, aggressive initial treatment may increase toxicity even mortality. 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.
METHODS: Newly diagnosed pediatric EBV-HLH patients (n=108) were risk-stratified by cytokine and clinical criteria. Six were excluded for protocol violations. Treatment was initiated accordingly and dynamically adjusted based on response.
RESULTS: Among the 102 evaluable patients, 61 and 41 patients were classified as low-risk and high-risk, and initially received dexamethasone treatment and HLH-94/04 regimens, respectively. By the 8th week of treatment, 85 patients (83.3%) had achieved complete remission. 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% ± 6.7%, with 91.8% ± 6.9% and 78.0% ± 12.7% for low-risk and high-risk patients, respectively (P = 0.037). Low-risk patients whose treatment shifting from dexamethasone to HLH-94/04 regimens presented similar 12-month OS with those initially treated with HLH-94/04 regimens (82.1% ± 14.1% vs. 78.0% ± 12.7%, P = 0.589). In multivariate COX regression model, risk group and response to initial treatment at 48-72 hours thereafter were associated with OS.
CONCLUSIONS: A cytokine- and clinical-based risk stratification system, combined with dynamic response assessment, enables tailored treatment for pediatric EBV-HLH patients. This approach facilitates precision therapy, avoids unnecessary chemotherapy, and prevents delays from effective treatment.
PMID:41172272 | DOI:10.1093/infdis/jiaf556
