Etoposide [1111 Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023;82:1271–85., 3232 Ehl S, Astigarraga I, von Bahr Greenwood T, Hines M, Horne A, Ishii E, et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018;6:1508–17., 3535 Bergsten E, Horne A, Arico M, Astigarraga I, Egeler RM, Filipovich AH, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: longterm results of the cooperative HLH-2004 study. Blood. 2017;130:2728–38.] (topoisomerase II inhibitor) |
50–150 mg/m2/ dose/week IV |
T lymphocytes |
Inhibits cell proliferation |
Bone marrow suppression, hepatotoxicity, nephrotoxicity, mucositis, alopecia, secondary malignant hypotension |
Ciclosporin [1111 Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023;82:1271–85., 3333 Halyabar O, Chang MH, Schoettler ML, Schwartz MA, Baris EH. Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Pediatr Rheumatol. 2019;17:7. https://doi.org/10.1186/s12969-019-0309-6. https://doi.org/10.1186/s12969-019-0309-...
, 3535 Bergsten E, Horne A, Arico M, Astigarraga I, Egeler RM, Filipovich AH, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: longterm results of the cooperative HLH-2004 study. Blood. 2017;130:2728–38.] (calcineurin inhibition) |
3–7 mg/kg/day q12 hr PO |
IL-2, IFNγ, others |
Inhibits cell proliferation and effector functions |
Nephrotoxicity, hypertension, hepatotoxicity, neurotoxicity, hirsutism, gingival hypertrophy |
Rituximab [1111 Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023;82:1271–85., 3636 Bakshi J, Hassan S, D'Cruz D, Chan A. Rituximab therapy in refractory macrophage activation syndrome secondary to systemic lupus erythematosus. Lupus. 2013;22(14):1544e6., 3737 Chellapandian D, Das R, Zelley K, Wiener SJ, Zhao H, Teachey DT, et al. Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens. Br J Haematol. 2013;162:376–82.] (anti-CD20 mAb) *EBV-MAS |
375 mg/m2/dose (maximum 1 g) q15 days IV or 375 mg/m2/dose (max 1 g) q7 days up to 4 consecutive weeks IV or 750 mg/m2/dose (max 1 g) q15 days IV |
B lymphocytes |
Depletes B lymphocytes |
Infusion reactions, hepatotoxicity, nephrotoxicity, hypertension, immunosuppression, cytopenia, IgG, progressive multifocal leukoencephalopathy |
Emapalumab [3838 Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med. 2020;382:1811–22.] (anti-IFNγ mAb) *Refractory HLH |
1–10 mg/kg/dose And then 3 mg/kg/ dose Every 3 days IV |
IFNg |
Neutralizes IFNg |
Immunosuppression (mycobacteria, herpesviruses and Histoplasma capsulatum), infusion reactions, hypertension |
Ruxolitinib [3939 Zhang Q, Zhao YZ, Ma HH, Wang D, Cui L, et al. A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis. Blood. 2022;139:3493–504.] (JAK 1/2 inhibition) |
2.5–20 mg/dose or 25 mg/m2/dose q12 hr PO |
IFNγ, IL-6, IL-12 and others |
Inhibits cytokine signaling |
Immunosuppression (herpesviruses), dyslipidemia, hepatotoxicity, cytopenia |
Plasmapheresis [4040 Kinjo N, Hamada K, Hirayama C, Shimizu M. Role of plasma exchange, leukocytapheresis and plasma diafiltration in management of refractory macrophage activation syndrome. J Clin Apheresis. 2018;33(1):117–20. https://doi.org/10.1002/jca.21570. https://doi.org/10.1002/jca.21570...
] |
|
Multiple cytokines |
Removes proinflammatory mediators |
Allergic reactions, fever, infections |