What is the initial treatment for Hemophagocytic Lymphohistiocytosis (HLH)?

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Last updated: June 5, 2025View editorial policy

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From the Guidelines

The initial treatment for Hemophagocytic Lymphohistiocytosis (HLH) should involve pulsed corticosteroids and elements of HLH-94, including dexamethasone 10 mg/m2 with or without a modified dose of etoposide, as recommended in the 2019 Blood journal study 1. The decision to start HLH-directed treatment depends on clinical judgment and assessment of organ function.

  • Key considerations include:
    • The use of pulsed corticosteroids, such as dexamethasone, to reduce inflammation
    • The administration of etoposide, which may be necessary in cases of severe HLH with imminent organ failure
    • The potential addition of IV immunoglobulin (IVIG) to inhibit complement activation and block antibody Fc fragments and macrophage Fc receptors
  • The treatment regimen should be individualized, taking into account the patient's renal function and other factors, such as age-specific norms, to determine the optimal dose of etoposide 1.
  • The duration of treatment is typically 8 weeks, after which patients should be evaluated for response and considered for maintenance therapy or allogeneic hematopoietic stem cell transplantation (alloSCT) if necessary 1.

From the Research

Initial Treatment for Hemophagocytic Lymphohistiocytosis (HLH)

The initial treatment for HLH varies depending on the underlying cause and the patient's condition.

  • For familial forms of HLH, chemotherapy is used as a bridge to hematopoietic stem cell transplantation 2.
  • In cases of HLH occurring in rheumatic disease (macrophage activation syndrome), treatment options include glucocorticoids, IL-1 blockade, or cyclosporine A 2.
  • For other forms of HLH, addressing the underlying trigger is essential 2.
  • Immunosuppressive treatment protocols have been refined, and experience is gaining with alternative and salvage approaches 3.
  • Treatment of pediatric HLH using HLH-2004 or multi-agent chemotherapy can be applied in adult patients, although the dose and type of drug need to be adjusted 4.
  • Allogenic hematopoietic stem cell transplantation is highly recommended for patients who become reactivated or are refractory to the initial treatment as soon as possible to improve survival 4.

Key Considerations

  • Prompt diagnosis and treatment are essential due to the high mortality rate of HLH, especially in adults 2, 3.
  • The clinical spectrum of HLH in adults ranges from mild and self-limited to rapidly fatal multiorgan failure 5.
  • Many questions remain unresolved regarding the diagnosis and treatment of HLH in adults, highlighting the need for ongoing education and research 3, 5, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy.

Best practice & research. Clinical rheumatology, 2020

Research

Hemophagocytic Lymphohistiocytosis: Clinical Presentations and Diagnosis.

The journal of allergy and clinical immunology. In practice, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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