Accelerated response and reduced chemotherapy with ruxolitinib-based regimen therapy in pediatric hemophagocytic lymphohistiocytosis: a retrospective comparison with HLH-94 regimen

Objective To compare the efficacy of a Ruxolitinib-based regimen versus the conventional HLH-94 protocol in children with newly diagnosed hemophagocytic lymphohistiocytosis (HLH). Methods This single-center, retrospective historical control study enrolled 67 pediatric HLH patients who met the HLH-2004 diagnostic criteria. Patients treated with the HLH-94 regimen (dexamethasone plus etoposide) from 2022 to 2023 constituted the control group (Group C, n=40), while those treated with a response-guided, ruxolitinib-based regimen from 2024 comprised the treatment group (Group T, n=27). Primary endpoint was 12-month overall survival (OS). Secondary endpoints included early response, safety, and cumulative exposure to glucocorticoids and etoposide during the first 8 weeks of therapy. Results Group T achieved a significantly higher complete response (CR) rate at week 2 compared to Group C (25.9% vs. 0%; P = 0.001). CR rates at weeks 4 and 8 were 55.5% vs. 35.0% (P = 0.096) and 78.0% vs. 70.0% (P = 0.481), respectively, with no significant difference in overall response rate. The 12-month OS (96.3% vs. 92.5%) and EFS (74.1% vs. 77.5%) rates did not differ significantly (P>0.05). Serial laboratory monitoring revealed that Group T exhibited faster hematological recovery and earlier neutrophil normalization (by week 2 vs. week 4) (P < 0.001). Key inflammatory markers (ferritin, IFN-γ, IL-10) declined rapidly in both groups. Crucially, the ruxolitinib-based strategy drastically reduced chemotherapy exposure: a significantly lower proportion of patients in Group T received glucocorticoids (66.7% vs. 100%, P<0.001) and etoposide (41.7% vs. 100%, P<0.001), and a significantly different distribution of glucocorticoids(Group T median: 60mg/kg (IQR: 0, 60); Group C median: 60mg/kg (IQR:60, 60); P = 0.012)and etoposide(Group T median: 0mg/m2 (IQR: 0, 885.5mg/m2); Group C median: 900mg/m2 (IQR:900, 1000); p=0.000) The incidence of secondary infections and treatment-related laboratory abnormalities (TBil, AST, ALT, or Scr) was comparable between groups. Conclusion For pediatric HLH, a ruxolitinib-based regimen is a viable and effective therapy. It facilitates more rapid complete remission and markedly reduces chemotherapy exposure, particularly to etoposide, while preserving high short-term survival with an acceptable safety profile. This study provides a compelling rationale for future prospective randomized controlled trials to confirm the long-term benefits and safety of this approach.