How i treat primary haemophagocytic lymphohistiocytosis

Abstract

Primary haemophagocytic lymphohistiocytosis (HLH) diseases are a collection of inherited genetic disorders that cause the syndrome of HLH. Great advances have been made in the last 20 years with regard to the discovery of many of the genetic aetiologies of disease. Several advances have also been made on the clinical stage. Accurate screening diagnostics for primary HLH diseases that are superior to traditional Natural Killer cell function testing have been developed and are now available in many countries. There is now grounded clinical experience on which to base routine treatment decisions for patients with HLH. Newer approaches to allogeneic haematopoietic cell transplantation have increased overall patient survival. Despite these advances, however, there is still much work to be done to further improve patient care. This 'How I Treat' article will focus on summarizing current diagnostic, treatment and transplant strategies for patients with primary HLH diseases.

STXBP2-R190C Variant in a Patient With Neonatal Hemophagocytic Lymphohistiocytosis (HLH) and G6PD Deficiency Reveals a Critical Role of STXBP2 Domain 2 on Granule Exocytosis

“…In addition to the STXBP2 (c.568C>T; Arg190Cys) mutation, the patient also carries a mutation associated with G6PD deficiency. He met 6 of the 8 clinical criteria for HLH: splenomegaly, fever, hypertriglyceridemia, hemophagocytosis, extremely elevated ferritin, and elevated soluble IL-2 receptor ( 1 ). Liver dysfunction findings and the abnormal CD107a degranulation assay further supported the neonatal HLH diagnosis.…”

“…Neonatal hemophagocytic lymphohistiocytosis (HLH) is a medical emergency that can be associated with significant morbidity and mortality. Patients can present a diagnostic dilemma, especially when the presentation is deemed atypical ( 1 , 2 ). Newborns and infants manifesting with HLH often have a genetic determined HLH, also known as familial HLH (f-HLH) ( 3 – 5 ).…”

Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis

“…No standardized treatment exists for relapsed or refractory hemophagocytic lymphohistiocytosis; however, individual case reports involving patients who have received biologics and small case series involving patients who have received alemtuzumab (an anti-CD52 monoclonal antibody) and antithymocyte globulin have shown efficacy in some patients. [9][10][11][12] Mounting evidence provides support for the pivotal pathogenic role of interferon-γ in hemophagocytic lymphohistiocytosis. Elevated interferon-γ levels in patients with hemophagocytic lymphohistiocytosis correlate with active disease, 4,[13][14][15][16] and neutralization of interferon-γ in models of hemophagocytic lymphohistiocytosis in mice allowed most of the mice to survive, reduced signs and symptoms, or both.…”

Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders

“…Some additional primary immune deficiencies have been reported to present with HLH, for example severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome, chronic granulomatous disease, and STAT1 gain of function, among others. 18,[38][39][40] Several metabolic diseases also predispose to the development of HLH. [41][42][43][44] With sequencing costs and analysis times going down, whole exome sequencing and even whole genome sequencing will provide more comprehensive solutions for detecting underlying genetic causes of HLH.…”