1. Introduction
Hemophagocytic lymphohistiocytosis (HLH) is one of the life-threatening diseases in pediatric patients. 1 An incidence of HLH, which previously considered as a rare condition, was reported up to 1 case per 3,000 inpatient admissions in a tertiary care pediatric hospital. 2 HLH is categorized as (1) primary HLH which is associated with genetic mutations including familial HLH and partial oculo-cutaneous albinism with HLH, and (2) secondary HLH which is related to infections (infection-associated hemophagocytic syndrome, IAHS), malignancies (malignancy-associated hemophagocytic syndrome, MAHS), and rheumatologic diseases (macrophage activation syndrome, MAS-HLH). The classic clinical manifestation of HLH is “sepsis-like” illness which mimics children with septic shock. 3HLH-2004 criteria are typically used to diagnose this fatal disease.4 Moreover, there are several specific criteria for rheumatologic diseases complicated with MAS-HLH. 5, 6The standard HLH treatment protocol comprises of immunosuppressive agents and chemotherapy. Allogeneic hematopoietic cell transplantation is reserved for patients with primary HLH, central nervous system (CNS) involvement, and relapsed/refractory disease. 1, 3
A recent multicenter study in Thailand revealed that 20.5% of children with HLH died within 1 month of diagnosis. The major cause of death was relapsed or refractory disease (R/R HLH). 7 Although several prognostic factors for early mortality in childhood HLH have been proposed, risk factors for R/R HLH in children remain limited. Previously published predictive factors for R/R HLH have typically focused on parameters following treatment initiation. These include younger age, persistent thrombocytopenia, consistently high Epstein-Barr Virus (EBV) viral load, CNS involvement, and the use of treatment protocols excluding etoposide. 8-10
In many developing countries, including Thailand, treating R/R HLH with allogeneic hematopoietic cell transplantation often involves a long waiting time. Detecting children with risk factors for R/R HLH and initiating early intervention for these patients are considered viable options in these settings. The primary objective of the study was to identify prognostic indicators for children with R/R HLH at the time of diagnosis. Its secondary objectives included evaluating the incidence of R/R HLH in children and assessing their survival rates.