Treatment outcomes and prognostic factors for non- malignancy associated secondary hemophagocytic lymphohistiocytosis in children

Abstract

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome that requires prompt diagnosis and appropriate treatment. A risk-stratification model that could be used to identify high-risk pediatric patients with HLH who should be considered for second-line therapies, including salvage regimens and allogeneic hematopoietic cell transplantation (HCT), was developed.Methods: The medical records of 88 pediatric patients (median age 1.4 years, range 0.2-15 years) with non-malignancy associated secondary HLH were retrospectively reviewed. Treatment strategies included dexamethasone, etoposide, and cyclosporine. Results:Survival analysis showed patients with Epstein-Barr virus(EBV)-HLH experienced better 5-year overall survival (OS) than patients with HLH due to other infections and unknown causes, autoimmune disease, or immunodeficiency (80% vs. 77%, 65%, 11%, p<0.001). On multivariate analysis, among all patients, non-response at 8 weeks was the most powerful predictor of poor OS. When treatment response was excluded, hemoglobin <60g/L and albumin <25g/L at diagnosis were associated with poor OS. In patients with EBV-HLH, hemoglobin <60g/L at diagnosis was associated with poor OS. A prognostic risk score was established and weighted based on hazard ratios calculated for three parameters measured at diagnosis: hemoglobin <60g/L (2 points), platelets <30x109/L (1 point), albumin < 25g/L (2 points). Five-year OS of low-risk (score 0-1), intermediate-risk (score 2), and poor-risk (score ≥3) patients were 88%, 38%, and 22%, respectively (p<0.001).Conclusions: These findings indicate that clinicians should be aware of predictive factors at diagnosis and consider 8-week treatment response to identify patients with high-risk of disease progression and the need for second-line therapy and allogeneic HCT.

The first pediatric case of hemophagocytic lymphohistiocytosis secondary to Crimean‐Congo haemorrhagic fever successfully treated with therapeutic plasma exchange accompanying ribavirin and intravenous immunoglobulin

“…TPE is an extracorporeal blood purification technique that remove antigen‐antibody complexes, autoantibodies, inflammatory cytokines, and other harmful factors endotoxins. Although TPE is not among the indications for secondary HLH in the guideline of American Society for Apheresis (ASFA), there have been few reports with secondary HLH successfully treated with a combination of TPE, IVIG, and MPZ 8‐10 . We considered that cytokine clearance and antibody‐blocking could be achieved via TPE and IVIG, respectively in our patient.…”

“…Etoposide and cyclosporin A can be started as salvage therapy for patients who do not improve with IVIG and MPZ. But this treatment regimen is highly toxic and can result in death 9 …”