To our knowledge, the two cases above are the first reported cases of relapsed, refractory HLH/MAS in patients with trisomy 21 successfully induced with emapalumab, an IFNγ antibody, and transitioned to a steroid sparing regimen with oral baricitinib, a JAK inhibitor, for maintenance interferon suppression. Here, IFNG is linked to hemophagocytic syndrome.