Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study
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 ca...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2024-02-01
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| Series: | Critical Care Explorations |
| Online Access: | http://journals.lww.com/10.1097/CCE.0000000000001046 |
| _version_ | 1827307999042994176 |
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| author | Laura Scholz, MD Florian Posch, MD, PhD Eduard Schulz, MD, PhD Max Gornicec, MD Albert Wölfler, MD Alexander C. Reisinger, MD, PhD Andreas Reinisch, MD, PhD Philipp Eller, MD Florian Eisner, MD Philipp Kreuzer, MD Martin Stradner, MD Alexander R. Rosenkranz, MD Florian Krammer, PhD Gernot Schilcher, MD Robert Krause, MD Stefan Hatzl, MD, PhD |
| author_facet | Laura Scholz, MD Florian Posch, MD, PhD Eduard Schulz, MD, PhD Max Gornicec, MD Albert Wölfler, MD Alexander C. Reisinger, MD, PhD Andreas Reinisch, MD, PhD Philipp Eller, MD Florian Eisner, MD Philipp Kreuzer, MD Martin Stradner, MD Alexander R. Rosenkranz, MD Florian Krammer, PhD Gernot Schilcher, MD Robert Krause, MD Stefan Hatzl, MD, PhD |
| author_sort | Laura Scholz, MD |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T18:49:49Z |
| format | Article |
| id | doaj.art-9d4850746bd04822b4d328e0793b3d35 |
| institution | Directory Open Access Journal |
| issn | 2639-8028 |
| language | English |
| last_indexed | 2024-04-24T18:49:49Z |
| publishDate | 2024-02-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Critical Care Explorations |
| spelling | doaj.art-9d4850746bd04822b4d328e0793b3d352024-03-27T03:41:02ZengWolters KluwerCritical Care Explorations2639-80282024-02-0162e104610.1097/CCE.0000000000001046202402000-00002Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot StudyLaura Scholz, MD0Florian Posch, MD, PhD1Eduard Schulz, MD, PhD2Max Gornicec, MD3Albert Wölfler, MD4Alexander C. Reisinger, MD, PhD5Andreas Reinisch, MD, PhD6Philipp Eller, MD7Florian Eisner, MD8Philipp Kreuzer, MD9Martin Stradner, MD10Alexander R. Rosenkranz, MD11Florian Krammer, PhD12Gernot Schilcher, MD13Robert Krause, MD14Stefan Hatzl, MD, PhD151 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.2 Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.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.1 Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.1 Intensive Care Unit, 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.1 Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.4 Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria.1 Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.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.http://journals.lww.com/10.1097/CCE.0000000000001046 |
| spellingShingle | Laura Scholz, MD Florian Posch, MD, PhD Eduard Schulz, MD, PhD Max Gornicec, MD Albert Wölfler, MD Alexander C. Reisinger, MD, PhD Andreas Reinisch, MD, PhD Philipp Eller, MD Florian Eisner, MD Philipp Kreuzer, MD Martin Stradner, MD Alexander R. Rosenkranz, MD Florian Krammer, PhD Gernot Schilcher, MD Robert Krause, MD Stefan Hatzl, MD, PhD Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study Critical Care Explorations |
| title | Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study |
| title_full | Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study |
| title_fullStr | Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study |
| title_full_unstemmed | Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study |
| title_short | Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study |
| title_sort | ruxolitinib iv immunoglobulin and high dose glucocorticoids for critically ill adults with secondary hemophagocytic lymphohistiocytosis a single center observational pilot study |
| url | http://journals.lww.com/10.1097/CCE.0000000000001046 |
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