Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study

Laura Scholz; Florian Posch; Eduard Schulz; Max Gornicec; Albert Wölfler; Alexander C Reisinger; Andreas Reinisch; Philipp Eller; Florian Eisner; Philipp Kreuzer; Martin Stradner; Alexander R Rosenkranz; Florian Krammer; Gernot Schilcher; Robert Krause; Stefan Hatzl

doi:10.1097/CCE.0000000000001046

Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study

Crit Care Explor. 2024 Feb 2;6(2):e1046. doi: 10.1097/CCE.0000000000001046. eCollection 2024 Feb.

Authors

Laura Scholz¹, Florian Posch², Eduard Schulz³, Max Gornicec⁴, Albert Wölfler², Alexander C Reisinger¹, Andreas Reinisch², Philipp Eller¹, Florian Eisner¹, Philipp Kreuzer⁵, Martin Stradner⁶, Alexander R Rosenkranz⁷, Florian Krammer^{8

9

10}, Gernot Schilcher¹, Robert Krause⁴, Stefan Hatzl^{1

8

9}

Affiliations

¹ Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
³ Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
⁴ Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁵ Emergency Department, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁶ Division of Rheumatology and Immunology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁷ Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁸ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.
⁹ Center for Vaccine Research and Pandemic Preparedness (C-VARPP), Icahn School of Medicine at Mount Sinai, New York, NY.
¹⁰ Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Abstract

Objectives: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality and frequently leads to ICU admission. Overall survival in adults with sHLH remains poor, especially in those requiring intensive care. Classical chemotherapeutic treatment exhibits myelosuppression and toxicity. Recently, inhibition of Janus kinase signaling by ruxolitinib has shown efficacy in pediatric HLH. We therefore aimed to determine the activity and safety of a ruxolitinib-based regimen, in critically ill adults with sHLH.

Design: Observational pilot study.

Setting: Single-center tertiary academic ICU.

Patients: Nine adults (≥ 18 yr) who fulfilled at least five of the eight HLH-2004 criteria.

Intervention: Triplet regimen combining: 1) ruxolitinib, 2) polyvalent human IV immunoglobulins (IVIG) at a dose of 1 g/kg bodyweight for 5 days, and 3) high-dose corticosteroids (CSs, dexamethasone 10 mg/m² body surface area, or methylprednisolone equivalent) with subsequent tapering according to the HLH-2004 protocol.

Measurement and main results: Nine patients (median age: 42 yr [25th-75th percentile: 32-54]; male: n = 6 males, median H-score: 299 [255-304]) were treated with the triplet regimen. The median Sequential Organ Failure Assessment score at HLH diagnosis was 9 (median; 25th-75th percentile: 7-12), indicating multiple-organ dysfunction in all patients. Within 10 days a significant decrease of the inflammatory parameters soluble interleukin-2 receptor and ferritin as well as a stabilization of the blood count could be shown. All patients were alive at ICU discharge (100% ICU survival), 1 patient died after ICU discharge because of traumatic intracerebral hemorrhage that might be related to HLH or treatment, corresponding to an overall survival of 86% in a 6 months follow-up period.

Conclusion: In this small case series, a triplet regimen of ruxolitinib in combination with IVIG and CS was highly effective and save for treating critically ill adults with sHLH.

Keywords: ICU; critical illness; hyperinflammation; ruxolitinib; tophemophagocytic lymphohistiocytosis.