Abstract 5856: Secondary hemophagocytic lymphohistiocytosis: A systematic review of incidence and prognostic outcomes
Authors: Maha Hameed, Gustavo Garcia, Kevin C. Zhen, Brooke A. Hartenstein, Laura D. Herrera, Utkarsh Acharya, Kai He, Karen Hamad, Wilhelmine Wiese-Rometsch
Journal: Cancer Research (2025)

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by immune system dysregulation of natural killer cells, cytotoxic CD8+ T-cells, and macrophages, resulting in malignant inflammation and multi-organ failure. Secondary HLH, often triggered by malignancies, infections, and/or autoimmune disease, typically affects adults. This systematic review investigated the characteristics and prognostic factors associated with secondary HLH. Methods: A systematic review was conducted in adherence to the PRISMA guidelines. A literature search was performed utilizing Medline, Embase, Scopus, Cochrane, and Clinicaltrials.gov databases without restricting to a starting date. Inclusion criteria encompassed retrospective or prospective, randomized, or non-randomized controlled studies published in English, focusing on adult patients over the age of 18 with secondary/acquired HLH. The primary outcomes of interest were overall survival (OS) and HLH-free/relapsed-free survival. Results: The systematic review yielded 23 eligible studies, including 2833 patients with a median age of 48.3 years and 1482 (52%) males. Most studies originated from China (48%), followed by Korea (13%) and the USA (13%). Malignancies, particularly lymphomas, and infections, notably Epstein-Barr virus (EBV), were identified as the most common underlying causes of secondary HLH. Two studies involved ICU-related secondary HLH diagnoses, whereby sepsis-associated HLH with gram-negative bacteremia, particularly E. coli (30%), was most implicated. OS was a ubiquitously reported outcome, with only two studies (9%) including HLH-free survival/HLH-relapse-free survival. Most frequently reported statistically significant worse prognostic factors in terms of OS included older age in 8 (35%), low platelets &amp;lt;100 in 7 (30%), and malignancy-associated HLH in 7 (30%) studies. Two studies demonstrated worse prognosis in terms of HLH-free survival. Other poor OS prognostic factors included EBV-associated HLH in 6 (26%), low fibrinogen in 5 (22%), elevated AST in 5 (22%), elevated LDH &amp;gt;400 in 4 (17%), high bilirubin in 4 (17%), albumin &amp;lt;2.8 g/dL in 4 (17%), male sex in 3 (13%), ferritin &amp;gt;2000 in 3 (13%), low hemoglobin in 3 (13%), prolonged APTT in 3 (13%), prolonged PT in 3 (13%), elevated creatinine in 2 (9%), elevated sCD25 in 2 (9%) and elevated IL-10 in 2 (9%). Least frequently reported were prolonged INR, fever, low total T3, and elevated beta-2-microglobulin. One study demonstrated that germline HAVCR2 mutation had a better prognosis. Conclusion: Older age, thrombocytopenia, and malignancy were the most common poor prognostic indicators for secondary HLH when indexed to outcomes of OS. This review also highlights a potential gap in the global understanding and documentation of secondary HLH, given the notable scarcity of studies from countries outside of China. Citation Format: Maha Hameed, Gustavo Garcia, Kevin C. Zhen, Brooke A. Hartenstein, Laura D. Herrera, Utkarsh Acharya, Kai He, Karen Hamad, Wilhelmine Wiese-Rometsch. Secondary hemophagocytic lymphohistiocytosis: A systematic review of incidence and prognostic outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5856.