Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis not associated with malignancy

Abstract

Hemophagocytic lymphohistiocytosis is an overwhelming systemic inflammatory process that is life-threatening if not treated appropriately. We analyzed prognostic factors of secondary hemophagocytic lymphohistiocytosis excluding malignancy. In this retrospective study, we analyzed 126 adult cases between 2001 and 2017. Treatment was based on dexamethasone with or without etoposide and cyclosporine. Patients who achieved complete response at 4 weeks were defined as early-stable responders, those who failed to achieve complete response but showed continuous improvement until 8 weeks as late responders, those whose conditions waxed and waned until 8 weeks as unstable responders. Patients with hemophagocytic lymphohistiocytosis caused by Epstein-Barr virus experienced worse 5-year overall survival compared to autoimmune disease, other infections, and unknown causes (25.1% vs. 82.4%, 78.7%, 55.5%, p<0.001). We observed that overall response rate at 4 weeks was similar, but decreased at 8 weeks in the Epstein-Barr virus subgroup from 75.5% to 51.0%, and finally decreased to 30.6%. Multivariate analysis revealed that 8-week treatment response was the most relevant factor for overall survival. Excluding 8-week response, Epstein-Barr virus, old age, hyperferritinemia, and thrombocytopenia were associated with poor survival. We established a prognostic model with the parameters: low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score≥3). These groups had 5-year overall survival of 92.1%, 36.8%, and 18.0%, respectively (p<0.001). We found that 8-week treatment response was a good predictive factor for overall survival, and that Epstein-Barr virus, old age, thrombocytopenia, and hyperferritinemia were associated with poor survival outcomes. Physicians should take care to identify high-risk patients for appropriate treatment strategies.

Risk factors of early death in adult patients with secondary hemophagocytic lymphohistiocytosis: a single-institution study of 171 Chinese patients

“…Additionally, age is also an independent prognostic factor. Elderly patients had shorter survival time, in consonance with the results of other studies [13,29]. It may be due to senescent organs resulting in more severe organ dysfunction [24] or other comorbid illnesses affecting the outcomes of HLH.…”

“…Thrombocytopenia was considered as a consistent prognostic factor in HLH [13,[21][22][23][24]. Similarly, our results also found that platelet less than 39.5 × 10 9 /L was an independent risk factor of 30-day survival.…”

“…A review showed that a marked hyperferritinemia over 50,000 mg/L was not seen most often in adult HLH patients, but in patients with renal failure, hepatocellular injury, infections and hematological malignancies [34]. Recent data had reported that hyperferritinemia was also an independent prognostic variable of mortality in HLH patients [13,14]. In our study, we found a significant correlation between hyperferritinemia and 30-day OS in univariate, but not multivariate analysis.…”

“…In fatal HLH, death usually occurs during the first 4-8 weeks due to multiple organ failure, bleeding or sepsis [12]. Currently, a series of studies have reported prognostic factors for long-term survival in HLH [13][14][15]. However, the factors influencing its early death are not completely elucidated.…”

Reevaluating the role of ferritin in the diagnosis of adult secondary hemophagocytic lymphohistiocytosis

“…If the scenario in question is indeed suspicious for HLH (eg, unexplained high‐fevers in an immunodeficient host or severe sepsis unresponsive to directed antimicrobial therapy), we may consider further directed testing such as measurement of soluble interleukin‐2 receptor level or bone marrow aspiration and biopsy (among other investigations). Of note, some prior studies have suggested that degree of hyperferritinemia may be predictive of mortality among HLH patients; however, among our cohort this relationship was not statistically significant …”