From the Guidelines
The treatment for Hemophagocytic Lymphohistiocytosis (HLH) typically involves a combination of immunoglobulins, glucocorticosteroids, cyclosporin A, and etoposide (VP16).
Treatment Options
- The mainstays of treatment for primary and infection-associated secondary HLH are:
- Immunoglobulins
- Glucocorticosteroids
- Cyclosporin A
- Etoposide (VP16) 1
- A combination of the latter three has been used in the HLH-94 and HLH-2004 protocols 1
- Anti-thymocyte globuline (ATG) has shown efficacy in a cohort of mainly primary HLH patients and alemtuzumab (anti-CD52) has been shown beneficial as a salvage agent in a limited number of patients 1
- Anti-interleukin-1 treatment can be used for HLH in auto-inflammatory conditions, in addition to glucocorticosteroids, cyclosporin A, and etoposide 1
Specific Treatment Approaches
- For Malignancy-Associated HLH, the treatment approach is not well established, but etoposide has been shown to be beneficial in some cases 1
- For HLH triggered by a T-cell lymphoma, the prognosis is worse than for HLH occurring in the setting of a B-cell lymphoma 1
- In adults, HLH-associated mortality remains high, especially in patients with underlying malignancies, and novel agents such as ruxolitinib, anakinra, alemtuzumab, and emapalumab are being investigated 1
Important Considerations
- Early recognition and diagnosis of HLH are essential for efficacious management 1
- A personalized and graded treatment approach is advised, taking into account the underlying trigger and the severity of HLH 1
- The treatment of HLH in adults may differ from that in children, and a modified diagnostic approach and individualized tailoring of treatment duration may be necessary 1
From the Research
Treatment Overview
The treatment for Hemophagocytic Lymphohistiocytosis (HLH) aims at suppressing hypercytokinemia and eliminating the activated and infected cells 2. The recommended therapeutic guideline for HLH was published by the Histiocyte Society in 1994 and revised in 2004, which greatly improved the survival in patients with HLH 3.
Treatment Protocols
- The HLH-94 treatment protocol includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by hematopoietic stem cell transplantation (HSCT) in patients with familial, persistent, or recurrent disease 4.
- The HLH-2004 protocol is used in the diagnosis of HLH and still forms the basis of the diagnosis of HLH in adults, although its use in adults has not been formally validated yet 5.
- Treatment modalities include immunosuppressive, immunomodulatory, and cytostatic drugs; T-cell antibodies; and anticytokine agents 2.
Hematopoietic Stem Cell Transplantation (HSCT)
- HSCT is needed for the correction of the immune defect in genetic HLH 2.
- Allogeneic hematopoietic stem cell transplantation after HLH remission represents the final solution for replacing defective cytotoxic T cells and even treating some underlying disease processes to prevent disease recurrence 3.
Individualized Approach
- Treatment of HLH in adults requires a more individualized approach depending on the underlying trigger, disease severity and course, as well as genetic background 6.
- The preferred approach should reflect a disease- and risk-adapted treatment that includes rigorous supportive care with continuous reassessment of sequential therapeutic measures 6.