Hemophagocytic lymphohistiocytosis (HLH) comes in two forms, a primary, genetic form and a secondary form. The primary form is caused by mutations in genes encoding proteins required for lymphocyte cytotoxicity and has a median survival of 1-2 months without adequate therapy. The secondary forms of HLH are often associated with infections, malignancies or systemic autoimmune diseases. In primary HLH, also called familial hemophagocytic lymphohistiocytosis (FHL), survival has increased from around 0% to around 55% in the international HLH studies run by the HLH Study Group of the Histiocyte Society. These treatments include chemo-immunotherapy with etoposide, corticosteroids, and cyclosporine A (CSA), and in primary HLH also hematopoietic stem cell transplant (HSCT). While milder forms of secondary HLH may respond to corticosteroids, CSA, and/or intravenous immunoglobulins (IVIG), severe secondary HLH will often require the addition of etoposide.
Macrophage activation syndrome (MAS), also called rheuma-associated hemophagocytic lymphohistiocytosis (Rh-HLH), is a severe complication of systemic autoimmune disorders. MAS/Rh-HLH has several clinical and laboratory similarities to other forms of HLH, and is potentially life threatening. They may also be associated with potentially severe CNS affection. However, despite the success of using etoposide in other forms of HLH, the experience on the use etoposide in MAS/Rh-HLH is limited.
We will report our experience at the Karolinska Children’s Hospital on the care of patients with severe MAS/Rh-HLH, some of whom had severe CNS-involvement, where the clinical development prompted us to initiate chemo-immunotherapy including etoposide. All patients responded well and without severe side effects to weekly etoposide (75-100 mg/m2), as a complement to pulses with high-dose methylprednisolone.
We conclude that chemo-immunotherapy including etoposide is worth considering in severe MAS/Rh-HLH and that initiation of this therapy should not be delayed in severely sick patients.
Disclosure of Interest J.-I. Henter Consultant for: NovImmune SA
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