Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by the activation of the mononuclear phagocytic system. The diagnosis of HLH in adults is challenging not only because the majority of the reported data are from pediatric patients, but also because HLH occurs in many disease entities. This study reports the clinical and laboratory findings and prognostic factors of adult HLH in a large cohort managed at a single medical center from 2003 to 2014. Seventy-three patients met the HLH-2004 diagnostic criteria. The median age was 51 years (range, 18-82 years); 41 (56.2%) were male. Patients manifested fever, cytopenias, and elevated ferritin in >85% of cases. Likely causes of HLH were as follows: 30 (41.1%) infections, 21 (28.8%) malignancies, 5 (6.8%) attributed to autoimmune disorders, 1 (1.4%) primary immunodeficiency, 2 (2.7%) post solid organ transplantation, and 13 (17.8%) idiopathic. The median overall survival was 7.67 months. Patients with malignancy-associated HLH had a markedly worse survival compared with patients with non-malignancy-associated HLH (median overall survival 1.13 vs. 46.53 months, respectively; P < 0.0001). In a multivariable analysis, malignancy (hazard ratio 5 12.22; 95% CI: 2.53-59.02; P 5 0.002) correlated with poor survival. Ferritin >50,000 mg/L correlated with 30-day mortality. Survival after a diagnosis of HLH is dismal, especially among those with malignancy-associated HLH. The development of a registry for adults with HLH would improve our understanding of this syndrome, validate diagnostic criteria, and help develop effective treatment strategies.

Human Granulocytic Anaplasmosis as a Cause of Febrile Illness in Korea Since at Least 2006

“…31 HLH is a severe and fatal clinical syndrome characterized by uncontrolled inflammatory responses, of which the fatality rate is 52.1-79.6%. 32,33 HLH can occur as primary and secondary forms, and infection is a major cause (∼49%) of secondary HLH. 34 The most common pathogen is Epstein-Barr virus, but zoonotic diseases including many rickettsial diseases and severe fever with thrombocytopenia syndrome, a tick-borne viral disease emerging in East Asia, are important causes of HLH.…”

“…32,33,[37][38][39] The therapeutic agents for HLH are combinations of cytotoxic agents and immunosuppressive drugs, including etoposide, cyclosporine A, and dexamethasone (HLH-2004 protocol). 39 Treatment of secondary HLH depends on its cause, and targeted antimicrobial therapy is the cornerstone.…”

Proliferation through activation: hemophagocytic lymphohistiocytosis in hematologic malignancy

“…78 Levels of ferritin above are known to correlate to increased morbidity and mortality, and in malignancy-induced HLH, a ferritin level .50 000 mg/L correlated to 30-day mortality. 83 On physical examination, edema and splenomegaly were also associated with a poor outcome.…”

“…83 Lymphoma is an adverse risk factor, but within lymphoma B-cell lymphomas were found to have positive outcomes over T-/NK cell-derived lymphomas. 84 This may be due to a superior prognosis of B lymphomas in general, but analysis of cases within the Mitelman database demonstrated that there was no significant difference in survival.…”

Características clínicas y mortalidad de pacientes adultos con síndrome hemafagocítico, estudio de cohorte retrospectiva

“…Identificar la clínica asociada a desarrollo del SHF podría ser de vital importancia para el reconocimiento del mismo de manera precoz [7][8][9][10] . Debido al impacto de este síndrome y al potencialmente frecuente subdiagnóstico, el objetivo de este estudio fue describir las características, presentación clínica, causas y sobrevida asociadas al SHF.…”