RT Journal Article
SR Electronic
T1 Efficacy of moderately dosed etoposide in macrophage activation syndrome - hemophagocytic lymphohistiocytosis (MAS-HLH)
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.200941
DO 10.3899/jrheum.200941
A1 AnnaCarin Horne
A1 Tatiana  von Bahr Greenwood
A1 Samuel C.C.  Chiang
A1 Marie Meeths
A1 Caroline Björklund
A1 Maria Ekelund
A1 Peter Erensjö
A1 Stefan Berg
A1 Stefan Hagelberg
A1 Yenan T.  Bryceson
A1 Ulf Andersson
A1 Jan-Inge Henter
YR 2021
UL http://www.jrheum.org/content/early/2021/02/10/jrheum.200941.abstract
AB Objective Macrophage activation syndrome (MAS) constitutes one 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 to 5-10%. Here we report our experiences with moderately dosed etoposide in severe MAS-HLH, administered with the objective to effectively reduce severe hyperinflammatory activity with limited side effects. Methods In addition to conventional anti-inflammatory treatment, moderately dosed etoposide was administered to seven children affected by rapidly progressing MAS-HLH with central nervous system (n=5) and/or pulmonary (n=5) involvement. Three had underlying systemic onset juvenile idiopathic arthritis (sJIA), two atypical sJIA (no arthritis at diagnosis), and two systemic lupus erythematosus. We performed lymphocyte cytotoxicity analyses in all seven and genetic analyses in six. Results All children promptly responded to moderately dosed etoposide (50-100 mg/m2 once weekly), added to conventional MAS-HLH treatment which was considered insufficient. The mean accumulated etoposide dose was 671 mg/m2 (range 300-1,050 mg/m2), as compared to 1,500 mg/m2 recommended the first 8 weeks of the HLH-94/HLH-2004 protocols. One child developed neutropenic fever and another neutropenic sepsis (neutrophils 0.3x109/L at therapy onset). Five/seven children had low percentages (<5%) circulating NK-cells prior to or in association with diagnosis; NK-cell activity was pathologically low in two/five children studied. Disease-causing variants in HLH-associated genes were not found. All children were alive at latest follow-up (2-9 years after onset); neurological symptoms had normalized in four/five affected children. Conclusion Moderately dosed etoposide may be beneficial in severe and/or refractory MAS-HLH.