Prognostic Factors of Adult Hemophagocytic Lymphohistiocytosis and Clinical Utility of HLH-2004 Diagnostic Criteria and HScore: A Real-World Multicenter Study from Thailand

Abstract

<b><i>Introduction:</i></b> Adult hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a dismal prognosis. Early diagnosis and prompt management are necessary for improved outcomes. <b><i>Methods:</i></b> This multicenter retrospective study investigated the etiologies, survival, and prognostic factors of HLH, including the utility of HLH-2004 criteria and HScore in real-life clinical practice. <b><i>Results:</i></b> A total of 147 HLH patients were identified by using a combination of hemophagocytosis identification in bone marrow and the HLH-related international classification disease-10. A total of 116 (78.9%) patients fulfilled the HLH diagnosis by HScore, while 91 (61.9%) patients fulfilled 5 of 8 HLH-2004 criteria. In Thailand, the clinical application of HLH-2004 criteria needed to be reduced from 8 to 6 due to a lack of sCD25 and natural killer cell activity tests. Using the adapted HLH-2004 with a cutoff value of 4 resulted in 132 (89.9%) cases meeting the diagnostic criteria. Among these 132 confirmed HLH patients by using adapted HLH-2004, HLH was triggered by infection (29.5%), autoimmune disease (12.9%), malignancy (40.9%), and unknown cause (16.7%). Median overall survival of HLH patients was extremely short (67 days). Ferritin &gt;6,000 μg/L, HLH from infection, malignancy, and unknown etiology were demonstrated as independent prognostic factors for inferior survival (hazard ratio [HR] 2.47; 95% confidence interval [CI] 1.39–4.37, HR 4.69; 95% CI 1.38–15.92, HR 6.09; 95% CI 1.84–20.14, and HR 6.02; 95% CI 1.64–22.05, respectively). <b><i>Conclusion:</i></b> Ferritin is a helpful biomarker for HLH diagnosis and prognostic prediction. Autoimmune disease-triggered HLH has favorable outcomes. Future prospective study is required to verify the use of the adapted HLH-2004 criteria.