Prognostic Features of Pediatric Primary Hemophagocytic Lymphohistiocytosis With CNS Involvement

In this study, we analyzed genetic variation and prognostic factors in pediatric primary hemophagocytic lymphohistiocytosis (pHLH) with central nervous system (CNS) involvement, based on data from patients treated at Beijing Children's Hospital between September 2017 and September 2022. A total of 67 pHLH patients were included, with a median age of 4.3 years. Our findings revealed distinct genetic mutation distributions between CNS-pHLH and pHLH without CNS involvement; specifically, CNS-pHLH patients had significantly fewer XIAP mutations but more PRF1 mutations ( P =0.006 and 0.002, respectively). In addition, the 3-year overall survival (OS) rate for CNS-pHLH patients was markedly lower compared with those without CNS involvement (50.2%±18.42% vs. 93.3%±9.02%, P <0.001). Hematopoietic stem cell transplantation (HSCT) was strongly associated with better prognosis in CNS-pHLH patients, yielding a 3-year OS of 82.0%±23.91% in transplanted patients, significantly higher than the 28.6%±19.40% in nontransplanted patients ( P <0.001). Furthermore, a Cox regression analysis identified PRF1 mutation, cerebrospinal fluid (CSF) soluble CD25 levels above 280 pg/mL, and elevated ferritin levels as independent risk factors for poor 3-year event-free survival (EFS) in CNS-pHLH ( P <0.05). These findings suggest that pHLH patients with PRF1 mutations should undergo regular CNS monitoring to prevent disease progression, and that HSCT may improve long-term prognosis in CNS-pHLH cases.