Etiologies and management of haemophagocytic lymphohistiocytosis: is it time for an updated protocol and targeted treatments?

Abstract

Objective: The objective of this study was to analyse the features, therapeutic approaches, and outcomes for adult patients with haemophagocytic lymphohistiocytosis (HLH) at a single centre.

Methods: This study was a retrospective chart review of all patients >18 years of age diagnosed with HLH according to HLH-2004 or H-score criteria at Ochsner Medical Center-New Orleans between 2013 and 2019.

Results: A total of 29 patients with HLH met inclusion criteria. A total of 7 patients had an underlying malignancy, 12 had an autoimmune disease, 2 were transplant patients, and 2 had a combination of malignancy, autoimmune disease, or immunodeficiency. A total of 6 patients developed HLH precipitated by infection alone. All 29 patients presented with fever. A total of 28 (97%) patients met H-score criteria, and only 20 (67%) met HLH-2004 criteria. Fifteen patients were treated with the HLH-2004 protocol. Of those treated with the HLH-2004 protocol, 73% (11/15) died, 8% (1/15) had recurrence of HLH, and 20% (3/15) had resolution of HLH. A total of 14 patients were treated with targeted therapy. Of those treated with targeted therapy, 93% (13/14) had resolution of HLH and 1 died. Targeted therapy included pulse steroids, tocilizumab, anakinra, IVIG, CSA, rituximab, and/or CYC in addition to antiviral or antibiotic therapy.

Conclusion: Our findings suggested that the rheumatologic patient population responded well to a targeted therapeutic approach and poorly to the HLH-2004 protocol. Whether the poor outcomes found with the use of the HLH-2004 protocol are secondary to the protocol itself or the aggressive nature of malignancy-associated HLH is unclear. Further studies are needed to develop tailored therapeutic regimens.

Keywords: JIA; SLE; adult-onset Still disease anti-cytokine therapy; haemophagocytic lymphohistiocytosis; macrophage activation syndrome.