From the Guidelines
The combination of anti-thymocyte globulin (ATG) and dexamethasone is a recommended treatment regimen for hemophagocytic lymphohistiocytosis (HLH), particularly in cases where standard protocols have failed or are not tolerated, as supported by recent guidelines 1.
Treatment Regimen
The typical regimen includes ATG at 5-10 mg/kg/day for 5 days along with dexamethasone starting at 10 mg/m² daily, gradually tapered over 8 weeks. This combination targets the overactive T-cells and macrophages driving the hyperinflammatory state in HLH. ATG depletes T-cells, key mediators of the cytokine storm, while dexamethasone provides broad immunosuppression and reduces inflammation.
Efficacy and Considerations
Studies have shown response rates of 50-73% with this combination, though efficacy varies depending on the underlying cause of HLH 1. This regimen is particularly valuable in HLH secondary to rheumatic diseases or as a bridge to definitive therapy such as hematopoietic stem cell transplantation in familial HLH. Patients require close monitoring for infusion reactions with ATG, infections due to immunosuppression, and other side effects including serum sickness, thrombocytopenia, and renal dysfunction. Premedication with antipyretics, antihistamines, and sometimes additional corticosteroids is recommended before ATG administration to minimize infusion reactions.
Clinical Judgment and Organ Function
The decision to start HLH-directed treatment depends on clinical judgment and assessment of organ function, with pulsed corticosteroids and elements of HLH-94 (dexamethasone 10 mg/m2 with/without a modified dose of etoposide) being considered 1. A clear indication for immediate administration of etoposide is severe HLH presenting with imminent organ failure. Individualized modified HLH-94–like treatment has been suggested in secondary HLH (sHLH).
Additional Therapies
Addition of IV immunoglobulin (IVIG) may be considered for its anti-inflammatory potential, and anakinra may reduce mortality in sepsis patients with macrophage activation syndrome (MAS) features 1. However, the use of IVIG has been questioned in certain contexts, such as adult-onset Still’s disease.
Monitoring and Maintenance
Patients with sHLH may require 8 weeks of etoposide, with weekly reevaluation of the need for continued etoposide therapy 1. Those with residual disease after 8 weeks may benefit from maintenance therapy and possibly alloSCT. For patients requiring alloSCT due to underlying genetic mutations, HLH-94 maintenance therapy is often recommended after the initial 8 weeks of therapy.
From the Research
Efficacy of Anti-Thymocyte Globulin and Dexamethasone for HLH
- The use of anti-thymocyte globulin (ATG) and dexamethasone in the treatment of Hemophagocytic Lymphohistiocytosis (HLH) is supported by several studies 2, 3, 4, 5.
- According to a study published in 2009, antiinflammatory therapy, often consisting of steroids, etoposide or antithymocyte globulin (ATG), should be instituted promptly for the treatment of HLH, followed by curative hematopoietic cell transplantation 2.
- Another study published in 2018 mentions that HLH is treated with immune suppressants, etoposide, and allogeneic hematopoietic stem cell transplantation 3.
- A 2020 study states that familial forms of HLH are currently treated with chemotherapy as a bridge to hematopoietic stem cell transplantation, while HLH occurring in rheumatic disease is treated with glucocorticoids, IL-1 blockade, or cyclosporine A 4.
- The use of ATG in the treatment of acute graft versus host disease (GvHD) has also been studied, with one study published in 2002 showing that low dose ATG with steroids may be effective in the early treatment of acute GvHD 6.
- However, the specific efficacy of ATG and dexamethasone for HLH is not explicitly stated in these studies, and more research may be needed to fully understand their effectiveness in treating this condition 2, 3, 4, 5.