Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by excessive lymphocyte and macrophage activation, leading to immune dysregulation and a cytokine storm. Early identification of factors associated with poor prognosis is essential to improving patient outcomes.
To identify predictors of mortality and recurrence of HLH in the context of inborn errors of immunity (IEI).
This retrospective longitudinal cohort study was conducted in the Pediatric Immuno-Haematology and Haematopoietic Stem Cell Transplant Department of the National Bone Marrow Transplant Centre in Tunis over 18 years (2005–2022). It included patients with IEI who developed HLH. Univariate analysis was performed to assess various clinical factors associated with mortality, followed by multivariate analysis using Cox regression to identify independent predictors.
Forty patients were included, 28 with primary HLH (70%) and 12 with secondary HLH (30%). The median age at symptom onset was 4 months (Q1 = 1.2, Q3 = 14.75). Univariate analysis identified several significant predictors of mortality, including age at first symptom ≤10 months (p = 0.01), age at activation diagnosis ≤6 months (p = 0.004), consultation delay >2 months (p = 0.03), clinical anemia with hemoglobin <7 g/dL (p = 0.03), neurological (p = 0.001), hepatic (p = 0.005), or renal (p = 0.02) failure during the first episode of HLH, absence of remission at day 15 (p = 0.01), and familial hemophagocytic lymphohistiocytosis (FHL) (p = 0.001). Multivariate Cox regression analysis identified two independent predictors of mortality: neurological failure (HR = 9.033, p = 0.021, CI [1.388–58.774]) and FHL (HR = 28.064, p = 0.002, CI [3.507–224.542]). HLH recurrence was independently associated with absence of remission within the first 15 days (HR = 4.211, p = 0.004, CI [1.075–23.577]), persistent elevated ferritinemia (HR = 3.848, p = 0.05, CI [1.001–15.218]), and persistent splenomegaly at day 30 (HR = 7.498, p = 0.017, CI [1.431–39.276]).
Neurological failure and FHL are independent risk factors for mortality in patients with IEI and HLH. Early identification and management of these factors are crucial to improving patient outcomes.
