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.