Predicting relapsed/refractory disease in childhood hemophagocytic
lymphohistiocytosis: A 13-year single-institute retrospective study in
Thailand
Abstract
Background: Hemophagocytic lymphohistiocytosis (HLH) is a
life-threatening disease. Relapsed/refractory disease is the main cause
of death. This study is aimed to determine the prognostic indicators for
relapsed/refractory disease in childhood HLH (R/R HLH).
Procedure: Infants and children under 18 years of age who were
diagnosed with HLH according to HLH-2004 criteria, MAS-HLH criteria for
rheumatologic diseases, or H-score undergoing treatment in Chiang Mai
University hospital between 2010 – 2022 were included. Demographic
data, clinical characteristics, and laboratory parameters were
retrospectively reviewed. Results: Out of 86 childhood HLH
cases, 30 patients (34.9%) experienced R/R HLH. All patients with
primary HLH developed R/R HLH. The most common form of secondary HLH was
infection-associated hemophagocytic syndrome (IAHS), comprising 43
cases. Of these, 37.2% had relapsed or refractory disease. Univariable
analysis identified several potential risk factors for R/R HLH,
including younger age, severe disease status, higher HLH-2004 criteria
scores, higher H-scores, overt DIC, higher pSOFA scores, and increased
levels of aspartate aminotransferase, total bilirubin, and direct
bilirubin. Multivariable logistic regression analysis revealed that a
pSOFA score of ≥ 8 and age < 3 years were independent risk
factors for R/R HLH, with adjusted odds ratios of 6.35 (95% confidence
interval [CI], 1.18 – 34.19; p = 0.032) and 3.62 (95% CI, 1.04 –
12.63; p = 0.044), respectively. Conclusions: Children with HLH
who have a pSOFA score of ≥ 8, or are younger than 3 years, are at a
higher risk of relapsed or refractory disease. Further evaluation of
management strategies in this context is warranted.