3.1 Demographic and baseline disease characteristics
In this cohort, 86 children diagnosed with HLH were included. Of these, 30 patients (34.9%), comprising 23 with refractory disease and 7 with relapsed disease, experienced R/R HLH. The most prevalent form of secondary HLH was IAHS, accounting for 43 cases, of which 37.2% developed relapsed or refractory disease. EBV was the predominant pathogen in IAHS, but only 2 out of 11 patients with EBV-IAHS progressed to R/R HLH. Among the 13 patients with MAHS, 46.2% developed R/R HLH, compared to 21.4% of the 28 patients with MAS-HLH. Systemic juvenile idiopathic arthritis (sJIA) was identified as the most frequent autoinflammatory disease leading to MAS-HLH. MAHS occurred frequently in patients with T-cell non-Hodgkin lymphoma (38.5%) and acute lymphoblastic leukemia (30.7%). Of note, two patients with primary HLH and one with MAHS who developed R/R HLH had molecular diagnoses ofRAB27A , LYST, and HAVCR2 mutations, respectively. Further details on each subgroup were provided in Supplemental Table S3.
The median age at diagnosis for the R/R HLH group was 2 years, which was younger than the median age of 5.2 years observed in the non-R/R HLH group (p=0.003). The R/R group also exhibited significantly higher scores in HLH-2004 criteria, H-scores, pSOFA scores, and modified ISTH-DIC scores. According to the Histiocyte Society’s severity grading, patients in this group presented with more severe disease. Table 1 presented an overview of the demographic data and disease characteristics of patients with and without R/R HLH.
The most frequent initial clinical sign and symptom of the R/R HLH group at diagnosis was fever, observed in 100% of the cases. This was followed by splenomegaly and hepatomegaly, each present in 93% of patients. Respiratory distress occurred in 77%, anemia in 73%, low mean arterial pressure12 (adjusted for age and without the need for inotropes) in 53%, and a Glasgow Coma Scale score of 13 to 14 in 40% of the cases. Details of the overall clinical presentation of patients with HLH were included in Supplemental Table S4.