Pediatric Hemophagocytic Lymphohistocytosis (HLH): A Single Institution Experience in the Diagnosis and Management of This Variable Disease

Background:

Hemophagocytic Lymphohistocytosis (HLH) is a rare disease that can be fatal if left untreated. We present a single institution series of pediatric patients diagnosed with HLH. Infants and children can present acutely ill with a febrile illness, and a high index of suspicion is required to make the diagnosis. Diagnosing HLH is challenging due to the rare occurrence, variable presentation, and nonspecific findings of this disorder. We report on 17 patients diagnosed with HLH in this series.

Methods:

This is a single institution review of pediatric cases of HLH diagnosed from 1996 to 2014 at the Medical University of South Carolina (MUSC).

Results:

A total of seventeen pediatric patients were diagnosed with HLH at the MUSC. All patients presented with vague symptoms. The median time from admission to diagnosis was 35 days. Age at presentation varied from 2 weeks to 19 years. Interestingly, 73 % of patients in our series are minorities. All patients met the diagnostic criteria for HLH with a median of 7/8 criteria. The median values for Hemoglobin, absolute neutrophil count (ANC), and platelet count were 9 g/dl, 905 cells/ul, and 47,00 cell/ul respectively. The median values for ferritin, triglycerides, and fibrinogen were 11,000 ng/ml, 265 mg/dl, and 128 mg/dl. The median Il-2 soluble activity level and NK functional activity levels were 6,144 unit/ml and 0% for patients who underwent testing.

Our patients were divided into two groups- those who received HLH directed therapy, and those who did not. Eleven patients were treated according to an HLH study (HLH-94 or HLH-2004). Two patients succumbed to disease, and a third patient experienced recurrence and and died.

Five of the treated patients were found to have genetic mutations. Two had a perforin gene mutation, and three had STXBP2 gene mutation. These five patients underwent hematopoietic stem cell transplant (Matched sibling-1, MUD-2, and UCB-2). All engrafted. Two patietns are surviving, disease free. Three patients died due to BMT complications including GvHD, Respiratory failure, and GI perforation.

Six patients met the diagnostic criteria and did not receive treatment. Two of the 6 showed signs of clinical improvement prior to the start of treatment, and 4 received supportive care with or without anti-viral treatment. For this group there was a trend toward higher ferritin values and higher platelet counts.

Viral infections were identified in 7/17 patients. Two patients with CMV infection required treatment. The remaining 5 patients had either EBV or HSV and did not require HLH directed therapy.

Conclusion:

There was no difference in the mean values for the diagnostic criteria between the group that received HLH therapy and the group that did not. Hemophagocytic Lymphohistocytosis is a rare disease and requires high index of suspicion for the diagnosis. For patients who were treated according to HLH protocols, 6/11 are alive and well. Three died due to BMT complications, and two patients died due to treatment related issues. Six patients met the diagnostic criteria but did not receive immuno-suppressive treatment, of those 4 had EBV, 1 had HSV, another did not have an identified viral infection. Our data suggest that patients with EBV viral associated HLH may spontaneously improve and not require HLH directed therapy.