Recent advances in the treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome

Abstract

Purpose of reviewThe approach to treating patients with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) has shifted in recent years with the aim to limit exposure to genotoxic agents, such as etoposide, yet dampen hyperinflammation by targeting the activity of specific HLH/MAS-associated cytokines. In this review, we discuss recent efforts to reduce the dose of etoposide and/or incorporate cytokine-targeted therapies for the treatment of HLH/MAS.Recent findingsThere is emerging evidence that reduced-dose etoposide and/or cytokine-targeted therapies, including agents that neutralize or inhibit signaling induced by interferon gamma, interleukin (IL)-1, IL-18, and IL-6, can effectively ameliorate the clinical and laboratory manifestations of HLH/MAS and improve overall outcomes.SummaryThe application of novel regimens containing lower doses of etoposide and/or cytokine-directed agents to treat HLH/MAS holds potential to dampen inflammation while minimizing therapy-associated toxicities. Nevertheless, further research is needed to better understand, which patients represent the most appropriate candidates to receive cytokine-targeted therapies, elucidate the optimal timing and dose of these therapies, and decipher whether they should be administered alone or in combination with conventional HLH-directed therapies, such as dexamethasone and standard-dose or reduced-dose etoposide.

Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis

“…While the treatment of inflammation in fHLH has historically hinged on the use of genotoxic agents, understanding this pathophysiology at the cellular level creates opportunities for further development of rationally designed therapies targeting critical points in this cycle. Many such therapies have already shown promise in patients with fHLH and related immune dysregulation syndromes ( 59 ). Ongoing research into these mechanisms of immune dysfunction will support further clinical trials aimed at improving outcomes for patients with fHLH and related disorders of the immune system.…”

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

“…Hemadsorption can also significantly reduce the high level of cytokines in the patient’s circulation ( 99 ). But unlike PE, hemadsorption does not require plasma separation and allows for simultaneous fluid removal ( 100 )( Figure 3 ). Recently, many reports have found that this treatment can rapidly reduce the level of IL-6 and IL-10, significantly improve hemodynamics, and without relevant associated adverse effects ( 101 , 102 ).…”

Pediatric Histiocytic Disorders: Morphology, Immunophenotype and Genetics

“…22 However, the diagnosis and treatment of familial HLH remain challenging. 24 Herein, we review the pediatric histiocytic disorders encountered in our hematopathology practice, focusing on the pathological features of morphology, immunophenotype, genetics, and clinical presentations (Tables 1 and 2).…”