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.