Chellapandian D, et al. - In order to gain further insights regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop hemophagocytic lymphohistiocytosis (HLH) within the context of multisystem (MS)-Langerhans cell histiocytosis (LCH) (hereafter referred to LCH-associated HLH), the authors conducted a retrospective, multicenter study and collected data regarding 384 patients diagnosed with MS-LCH between 2000 and 2015. Diagnostic criteria for HLH was met in 32 patients as per the primary providers, yielding an estimated 2-year cumulative incidence of 9.3% ± 1.6%. An increased risk of LCH-associated HLH was noted in independent association with patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement. They noted significantly poorer 5-year survival for Patients with MS-LCH who met the criteria for HLH compared with patients with MS-LCH who did not meet the criteria for HLH (69% vs 97%). Findings support making further efforts to improve the recognition and optimize the treatment of patients with LCH-associated HLH.