Clinical Characteristics of Hemophagocytic Lymphohistiocytosis in Adults with Central Nervous System Involvement

Purpose: Central nervous system (CNS) involvement in hemophagocytic lymphohistiocytosis (HLH) is characterized by neurological symptoms/signs, CNS imaging changes, and cerebrospinal fluid abnormalities. However, most reports of CNS-HLH focused on pediatric patients, and there were few clinical studies in adult patients. Therefore, we carried out this study to investigate clinical characteristics and prognosis of adult patients with CNS-HLH.

Methods: A retrospective analysis of adult patients with HLH from January 2010 to December 2021 was conducted. Clinical characteristics, assistant examination, treatment, and prognosis were analyzed.

Results: Among 166 HLH patients in our center, 16 patients (9.6%) had neurological symptoms and/or assistant examinations of CNS involvement. 1 was primary HLH; 11 were secondary to malignant tumor; 3 were secondary to infection; 1 was secondary to autoimmune disease. 13 patients (81.3%) showed CNS symptoms, and the most common symptom was dizziness/headache (43.8%). 12 patients underwent cranial CT or MRI, and 9 (75%) showed changes. 7 patients underwent cerebrospinal fluid examination, and 5 (71.4%) showed abnormal results. 5 patients underwent PET-CT, and all were normal. 7 patients underwent HLH genetic testing, 1 showed homozygous mutation of UNC13D C.2588G&GT; 5 showed unknown significance heterozygous mutations of HLH related genes. For patients who received anti-HLH and/or anti-lymphoma chemotherapy, who achieved CR/PR had significantly better OS than those with NR (Not reached V.S. 8 days, P<0.001). However, Patients who received CNS-HLH therapy had no statistically significant long-term survival compared with patients who received general HLH therapy (P=0.290). As for the analyses of effective factors on survival time, rash was the only independent risk factor.

Conclusions: CNS involvement in adult patients with HLH is not rare and the prognosis is poor. The clinical manifestations and etiology of these patients are heterogeneous. Early diagnosis through CNS examinations and treatment in time are essential to improve the prognosis of patients with CNS-HLH.

This work was supported by 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC21007).

Key words: Hemophagocytic Lymphohistiocytosis; Adults; Central Nervous System; Prognosis; Retrospective Study

Li:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.