%0 Journal Article %A AnnaCarin Horne %A Tatiana von Bahr Greenwood %A Samuel C.C. Chiang %A Marie Meeths %A Caroline Björklund %A Maria Ekelund %A Peter Erensjö %A Stefan Berg %A Stefan Hagelberg %A Yenan T. Bryceson %A Ulf Andersson %A Jan-Inge Henter %T Efficacy of Moderately Dosed Etoposide in Macrophage Activation Syndrome–Hemophagocytic Lymphohistiocytosis %D 2021 %R 10.3899/jrheum.200941 %J The Journal of Rheumatology %P 1596-1602 %V 48 %N 10 %X Objective Macrophage activation syndrome (MAS) constitutes 1 subtype of the hyperinflammatory syndrome hemophagocytic lymphohistiocytosis (HLH), and the term MAS-HLH was recently proposed for HLH with underlying autoimmune/autoinflammatory conditions. The mortality of MAS-HLH has been estimated at 5–10%. Here we report our experiences with moderately dosed etoposide in severe MAS-HLH; the objective was to effectively reduce severe hyperinflammatory activity with limited side effects.Methods In addition to conventional antiinflammatory treatment, moderately dosed etoposide was administered to 7 children affected by rapidly progressing MAS-HLH with central nervous system (n = 5) and/or pulmonary (n = 5) involvement. Three had underlying systemic juvenile idiopathic arthritis (sJIA), 2 had atypical sJIA (no arthritis at diagnosis), and 2 had systemic lupus erythematosus. We performed lymphocyte cytotoxicity analyses in all 7 and genetic analyses in 6.Results All children promptly responded to moderately dosed etoposide (50–100 mg/m2 once weekly), added to conventional MAS-HLH treatment that was considered insufficient. The mean accumulated etoposide dose was 671 mg/m2 (range 300–1050 mg/m2) as compared to 1500 mg/m2 recommended in the first 8 weeks of the HLH-94/HLH-2004 protocols. One child developed neutropenic fever and another neutropenic sepsis (neutrophils 0.3 × 109/L at therapy onset). Five of 7 children had low percentages (< 5%) of circulating natural killer (NK) cells prior to or in association with diagnosis; NK cell activity was pathologically low in 2 of 5 children studied. Disease-causing variants in HLH-associated genes were not found. All children were alive at latest follow-up (2–9 yrs after onset); neurological symptoms had normalized in 4 of 5 affected children.Conclusion Moderately dosed etoposide may be beneficial in severe and/or refractory MAS-HLH. %U https://www.jrheum.org/content/jrheum/48/10/1596.full.pdf