Adult Secondary Hemophagocytic Lymphohistiocytosis: A Mini-Review on Recent Developments

Review Article

Ann Hematol Onco. 2023; 10(5): 1434.

Adult Secondary Hemophagocytic Lymphohistiocytosis: A Mini-Review on Recent Developments

Thomas David B, MD, MPH¹*; Pacioles Toni, MD²

¹Department of Transplant Infectious Diseases, H. Lee Moffitt Cancer Center & Research Institute, USA

²Edwards Comprehensive Cancer Center, Cabel-Huntington Hospital, 1400 Hal Greer Blvd, Huntington, WV 25701, USA

*Corresponding author: Thomas David B Department of Transplant Infectious Diseases, H. Lee Moffitt Cancer Center & Research Institute, USA. Tel: (615) 330-6065 Email: [email protected]

Received: July 10, 2023 Accepted: August 12, 2023 Published: August 19, 2023


Hemophagocytic Lymphohistiocytosis, also known as HLH, is a group of disorders classified as a type of cytokine release syndrome triggering an abnormal activation of lymphocytes. First described in a pediatric case with viral trigger in 1979, the key features of this syndrome include rapid progression with high mortality and impaired immunity. Many different etiological triggers have been described since the initial case. The syndrome can have profound impacts on all body systems which is explored to some extent within this text. Several agents have been tried in the treatment of this condition, particularly with respect to sustained remission and mortality benefits overall. This review seeks to outline clinical presentation and prognostic factors of HLH as well as recent advances in clinical treatment. Trials are discussed from literature review outlining prognostic markers as well as a discussion of tried therapies, recent advances and emerging agents of interest. Significant progress has been made in recent years although this remains a very complex and challenging disease to treat and mortality also remains high.

Keywords: Hlh; Hemophagocytic; Lymphohistiocytosis; Review; Treatment; Developments


Hemophagocytic Lymphohistiocytosis, also called the Hemophagocytic Syndrome (Here after referred to as HLH) is a cytokine release syndrome with a variety of triggers leading to an abnormal proliferation of activated lymphocytes and histiocytes. This results in uncontrolled inflammation in a variety of organ systems manifesting with various symptoms. This syndrome was first described by Risdall, et al in 1979 in a case with a viral etiology as the suspected trigger [1]. Hallmark clinical features include fever, cytopenias resulting in impaired immunity, with a typically rapid clinical progression tending towards high mortality rates [2]. This article is not meant as a comprehensive review of the topic but will seek to outline the clinical features and general prognostic factors of HLH and to bring a spotlight to recent advances in our understanding of this clinical syndrome and its treatment.


As previously mentioned, this is a typically rapidly progressive syndrome with high mortality and thus earlier diagnosis and effective treatment is crucial towards improving survival. In the original study, 19 patients were reported with similar symptoms and a viral trigger suspected, the most common of which being the herpesviridae. Other studies have also been conducted citing infection as likely the most common trigger [2]. The signs and symptoms reported in this landmark study included fever and other constitutional symptoms, with peripheral cytopenia and other laboratory abnormalities particularly liver function including coagulation. Additionally, hepatosplenomegaly, lymphadenopathy and pulmonary infiltrates can be seen. Another common factor was immune dysfunction, particularly cell-mediated given the underlying process [1]. Many of these features were later factored into the HLH-94 and then the HLH-2004 diagnostic criteria that followed. A summarization of these criteria can be seen in Table 1 [4].

Citation: David BT, Toni P. Adult Secondary Hemophagocytic Lymphohistiocytosis: A Mini-Review on Recent Developments. Ann Hematol Onco. 2023; 10(5): 1434.