Clinical outcomes of adults with hemophagocytic lymphohistiocytosis treated with the HLH-04 protocol: a retrospective analysis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation in children that is increasingly being recognized in adults. Efficacy data for the HLH-04 protocol in adults is lacking. This study retrospectively analyzed 31 adult patients, median age 46 years, who received HLH-04 from 1/1/2004 to 5/1/2018. HLH etiology included malignancy (n = 9), autoimmune (n = 8), infection (n = 8), and idiopathic (n = 6). Eighteen patients were evaluable for response at week 4 with 7 having no response, 11 reaching partial response, and 0 reaching complete response (CR). Six patients eventually achieved CR at a median 195 days. The 1-year overall survival (OS) was 35% and median OS was 3.2 months. Univariate analysis showed shorter survival for hemoglobin <9 g/dL (HR 4.29, p = 0.003), platelets <100 × 10⁹/L (HR 4.06, p = 0.027), ANC <1 × 10⁹/L (HR 5.24, p = 0.001), and total bilirubin >1.2 mg/dL (HR 3.30, p = 0.022). Outcomes of adults treated with HLH-04 remain dismal and newer treatment modalities are needed.

Keywords:

• Hemophagocytic lymphohistiocytosis (HLH)
• immune activation
• etoposide
• corticosteroids

Acknowledgements

The study team would like to thank Hannah Sauer, PharmD for assistance in the development of the initial methodology for this project. These data were presented at the 35th Annual Meeting of the Histiocyte Society, Memphis, TN in November 2019.

Disclosure statement

Dr. Mrinal S. Patnaik is part of the advisory board for Stem Line Pharmaceuticals. Dr. Sameer A. Parikh received honoraria from Pharmacyclics, AstraZeneca, Genentech, Gilead, AbbVie (all money given to Mayo Clinic), and research funding from Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, and Ascentage Pharma. All other authors report no conflicts of interest.