Hemophagocytic lymphohistiocytosis and macrophage activation syndrome: two rare sides of the same devastating coin

Table 4 Other therapies for HLH/MAS [11, 29, 31,32,33, 35,36,37,38,39,40,41,42]

Therapeutic agent	Dosing	Target	Action	Adverse events
Etoposide [11, 32, 35] (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 [11, 33, 35] (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 [11, 36, 37] (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 [38] (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 [39] (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 [40]		Multiple cytokines	Removes proinflammatory mediators	Allergic reactions, fever, infections

Salvage therapies: Anti-thymocyte globulin (ATG) [41] and alemtuzumab (anti-CD52 mAb) [42]
IV Intravenous, mg Miligrams, PO Oral use, SC Subcutaneous, IL Interleucin, IFN Interferon, mAb Monoclonal antibody

ISSN: 2523-3106