Hemophagocytic lymphohistiocytosis (HLH) pediatric patients at risk of short-term mortality share certain features, such as impaired blood clotting, abnormal liver function, and multiple organ dysfunction syndrome, or MODS, according to a recent study.
These findings may help doctors identify children at high-risk and begin appropriate treatment early.
The study, “Clinical profiles and risk factors of 7-day and 30-day mortality among 160 pediatric patients with hemophagocytic lymphohistiocytosis,” was published in the Orphanet Journal of Rare Diseases.
HLH is a rare and life-threatening condition caused by an overactive immune system. The condition can be inherited through genetic mutations — when it’s then known as primary, or familial HLH — or it can be caused by an underlying condition, such as a viral infection, cancer, or an autoimmune disease. In such cases, it is called secondary HLH.
Although the disorder carries a high mortality rate, most studies have focused on long-term survival and little information is available concerning short-term mortality.
To learn more, researchers at Hunan Children’s Hospital, in China, now examined patient records for common factors that could be used to identify children with HLH at a higher risk of short-term mortality — specifically, death within seven days, and within 30 days, after hospital admission.
In total, records from 160 pediatric HLH patients were analyzed. The median age at hospital admission was 32 months, or just younger than 3 years, with a range from 1 month to 18 years.
Among the children involved in the analysis, 108 survived for more than 30 days after admission. Meanwhile, 46 (28.8%) died within 30 days; of these patients, 18 (11.3%) died within seven days. Six patients who survived for more than seven days were lost to follow-up at day 30.
Thus, the seven-day overall survival was 88.8% and the 30-day survival rate was 70.1%.
All of the patients who died within seven days had developed liver dysfunction, impaired blood clotting (coagulopathy), and MODS, the study found.
Other common features strongly associated with seven-day mortality were sepsis, or a severe inflammatory reaction to infection, myocardial damage — such as what occurs after a heart attack — shock, and respiratory failure. Being younger than age 1 also was significantly associated with seven-day mortality.
Sepsis, respiratory failure, impaired blood clotting, myocardial damage, and MODS also were associated with a high 30-day mortality risk. Conditions associated with 30-day, but not seven-day mortality included severe pneumonia and gastrointestinal disorders.
Among lab findings, elevated blood urea nitrogen, a measure of kidney function, and specific blood clotting measures at admission were significantly associated with a high mortality risk at both time points.
Decreased clotting factor I (fibrinogen) and globulin, as well as elevated total bilirubin — all tied to impaired liver function — significantly correlated with 30-day mortality, but not with seven-day mortality.
Further, the investigators also found that relatively fewer patients died within 30 days after hospital admission when using chemotherapeutic medications. In particular, patients who survived for over 30 days received etoposide, cyclosporin A, and dexamethasone.
“Early death before the initiation of chemotherapy were largely due to late diagnosis of HLH and rapid deterioration,” the researchers wrote.
This, they argued, demonstrates the need for improved early diagnosis and chemotherapy use, as well as better treatment strategies for children.
According to the team, “the identified risk factors could help to stratify [classify] patients with high risk of early death, and need to be considered in the development of treatment protocols,” they wrote, adding that “studies are needed to investigate how to initiate adequate HLH-directed treatment strategies for patients with high risk of early death.”