A multicenter study of patients with multisystem Langerhans cell histiocytosis who develop secondary hemophagocytic lymphohistiocytosis

Background Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a‐positive (CD1a+)/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors’ knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS‐LCH (hereafter referred to LCH‐associated HLH). Methods To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS‐LCH between 2000 and 2015. Results Of 384 patients with MS‐LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2‐year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS‐LCH, and nearly one‐third (31%) had evidence of an intercurrent infection. Patient age