A retrospective analysis of etiology and outcomes of hemophagocytic lymphohistiocytosis in children and adults

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe, life-threatening inflammatory condition if untreated. We aimed to investigate the etiologies, outcomes, and risk factors for death in children and adults with HLH. Methods: The medical records of patients who met the HLH criteria of two regional university hospitals in Korea between January 2001 and December 2019 were retrospectively investigated. Results: Sixty patients with HLH (35 children and 25 adults) were included. The median age at diagnosis was 7.0 years (range, 0.1-83 years), and the median follow-up duration was 8.5 months (range, 0-204 months). Four patients had primary HLH, 48 patients had secondary HLH (20 infection-associated, 18 neoplasm-associated, and 10 autoimmune-associated HLH), and eight patients had HLH of unknown cause. Infection was the most common cause in children (14/35, 40.0%), whereas neoplasia was the most common cause in adults (13/25, 52.0%). Twenty-eight patients were treated with HLH-2004/94 immunochemotherapy. The 5-year overall survival (OS) rate for all HLH patients was 59.9%. The 5-year OS rates for patients with primary, infection-associated, neoplasm-associated, autoimmune-associated, and unknown cause HLH were 25.0%, 85.0%, 26.7%, 87.5%, and 62.5%, respectively. Using multivariate analysis, neoplasm-induced HLH (p = 0.001) and a platelet count < 50 × 10 9 /L (p = 0.008) were identified as independent risk factors for poor prognosis in patients with HLH. Conclusion: Infection was the most common cause of HLH in children, while it was neoplasia in adults. The 5-year OS rate for all HLH patients was 59.9%. HLH caused by an underlying neoplasm or a low platelet count at the time of diagnosis were risk factors for poor prognosis.

Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature

“…Infections are the most frequent underlying cause, accounting for a half of all HLH cases, with nearly 70% being secondary to viruses, mainly Herpes virus [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In a review of nearly 2200 cases of adult HLH and several case reports, infections are associated with a worse outcome in the presence of underlying immunodeficiency or cancer, and requirement of intensive care unit admission [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Consistently, hematological and solid cancers are the second most frequent cause of secondary HLH [ 12 , 16 , 19 , 20 , 24 ].…”

“…In a review of nearly 2200 cases of adult HLH and several case reports, infections are associated with a worse outcome in the presence of underlying immunodeficiency or cancer, and requirement of intensive care unit admission [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Consistently, hematological and solid cancers are the second most frequent cause of secondary HLH [ 12 , 16 , 19 , 20 , 24 ]. The main association is lymphoma, particularly T-cell and aggressive NHL, which also carry the highest mortality [ 2 , 12 ].…”

“…Infections, particularly EBV and CMV, are the main precipitating factors in HLH secondary to NHL. Other hematologic conditions include Hodgkin lymphoma, Castleman disease, acute myeloid leukemia, and myelodysplastic syndromes [ 12 , 16 , 20 ]. Lastly, HLH is a rare complication of solid tumors too (pancreas, liver, pituitary cancer and neuroblastoma, etc.)…”

“…Less is known about the association of HLH with autoimmune diseases. Frequency is maximal for systemic lupus erythematosus (SLE, up to 6%), followed by Still’s disease, arthritis and inflammatory bowel diseases [ 12 , 19 , 20 , 23 , 25 ]. Interestingly, therapies impact on mortality, in that patients treated with high dose dexamethasone and etoposide display a mortality >70%, whilst those treated with targeted therapies (including tocilizumab, anakinra, rituximab etc.)…”

Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature

“…7,8 Common findings include unremitting fever, splenomegaly, cytopenia, coagulopathy, liver dysfunction, hemophagocytosis, hyperferritinemia, and, in many cases, neurologic abnormalities. 8 Considering this complex picture of nonspecific signs and symptoms, the Histiocyte Society published the revised HLH-2004 protocol guidelines (originally described as guidelines in 1991), in which 5 out of 8 diagnostic criteria must be fulfilled TA B L E 1 HLH-2004 and modified 2009 diagnostic criteria for HLH Traditional HLH-2004 Criteria 11 Modified HLH-2009 Criteria 12 1. A molecular diagnosis consistent with HLH # : 1.…”