A comprehensive analysis of adult patients with secondary hemophagocytic lymphohistiocytosis: a prospective cohort study

Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal condition with various underlying disorders in adult patients and is diagnosed based on the HLH-2004 criteria, which were established based on experience in pediatric patients. However, few studies have prospectively evaluated the treatment outcomes and diagnostic performance of HLH criteria in adult patients with secondary HLH. Thus, we performed a single-center, prospective cohort study of adult patients with suspected HLH, and we analyzed treatment outcomes of patients enrolled between 2017 and 2019 as an interim analysis (ClinicalTrials.​gov Identifier: NCT03117010). Of the 73 patients with suspected HLH, 70 patients completed the evaluation for ≥ 7 of the HLH-2004 criteria, and 55 patients were diagnosed with HLH (55/73, 75%). Although serum ferritin and fever had a sensitivity of more than 90%, both had exceptionally low specificity, whereas soluble CD25 had a sensitivity of more than 90% and specificity of 80%. Forty patients with malignancy-associated HLH had B cell (n = 19) or T- or NK-cell (n = 21) lymphoid malignancy, whereas 15 patients had non-malignant disorders. Non-malignancy-associated HLH had greater than 90% 1-year overall survival (OS) after diagnosis of HLH, whereas that for malignancy-associated HLH was less than 40%. In conclusion, our study showed promising treatment outcomes for patients enrolled in our prospective cohort study, and prospectively demonstrated the diagnostic performance of the HLH-2004 criteria in adult patients with suspected HLH. Given that lymphoma was the most common cause of HLH in adults, thorough evaluation for lymphoma should be performed in adults with suspected HLH.