Predicting relapsed/refractory disease in childhood hemophagocytic lymphohistiocytosis based on clinical features at diagnosis: A 13-year single-institute retrospective study in Thailand

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. Relapsed/refractory disease is the main cause of death. This study aims to determine the prognostic indicators for relapsed/refractory disease in childhood HLH (R/R HLH). 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 and 2022 were included. Demographic data, clinical characteristics, and laboratory parameters were retrospectively reviewed. 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. 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.