Pediatric hemophagocytic lymphohistiocytosis (pHLH) is a life-threatening condition characterized by aberrant immunopathology and systemic manifestations. The HLH-2004 protocol prioritizes urgent immunosuppressive therapy; however, timely diagnosis can be challenging due to rarity and symptom overlap with other pediatric pathologies. This study examines the outcome of pHLH at a tertiary care children’s hospital in Canada and aims to identify gaps to inform an institutional protocol.
This retrospective cohort study reviewed medical records of pHLH at a Canadian tertiary care children’s hospital between 2014 and 2025. Patients were identified using International Classification of Diseases (ICD) 10 diagnostic codes on discharge diagnosis and cross-referenced with oncology, immunology, and rheumatology clinic lists. Descriptive statistics were collected for the first admission with pHLH.
Nineteen patients met the inclusion criteria. The median age at presentation was 7 years (range: 1–16). Of these patients, 3 cases were primary HLH, and 16 were secondary. Secondary causes included infections (3/19, 16%), inflammatory/rheumatologic conditions (10/19, 53%), and malignancy (3/19, 16%). The mean length of stay was 44 days, and 10 patients required pediatric intensive care unit (PICU) admission (mean: 5 days). Overall mortality was 21% (4/19). Diagnosis and treatment were initiated an average of 7 days after presentation (range: 1–26). Nine patients met 2004 HLH criteria, 7 patients were considered to have macrophage activation syndrome (MAS), and the remaining 3 had an overlap presentation or post-mortem confirmation of diagnosis. Treatments included HLH-2004 protocol (5/19, 26%), high-dose/pulse methylprednisolone (8/19, 42%), solely dexamethasone/prednisone (5/19, 26%), intravenous immunoglobulin (IVIG) (7/19, 37%), and small molecule immunomodulation (anakinra, tocilizumab, alemtuzumab, and rituximab) (7/19, 37%). Three patients received a hematopoietic stem cell transplant (HSCT), 2 of these being primary HLH cases—both died from complications. The final primary HLH case remains awaiting HSCT. Among secondary cases, 1 patient received HSCT and another was scheduled, but died prior to. Seven patients experienced recurrence, with 4 readmitted more than 3 times.
Despite prompt diagnosis among inpatients, HLH is a high-mortality condition. Patients with secondary conditions that were identified and treated showed considerable improvement without the use of the HLH 2004 protocol. These findings will help inform institutional diagnostic and treatment protocols for HLH.
