Effective control of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis with immunochemotherapy

The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal d isorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV- HLH) remains uncertain, numerous reports indicate that it can also be fatal in a substantial proportion of cases. We therefore assessed the potential of immunochemotherapy with a core combination of steroids and etoposide to control EBV-HLH in 17 infants and children who met stringent diagnostic cri teria for this reactive disorder of the mononuclear phagocyte system. Treat ment of life-threatening emergencies was left to the discretion of particip ating investigators and typically included either intravenous Ig or cyclosp orin A (CSA). Five patients (29%) entered complete remission during the ind uction phase (1 to 2 months), whereas 10 others (57%) required additional t reatment to achieve this status. In 2 cases, immunochemotherapy was ineffec tive, prompting allogeneic bone marrow transplantation. Severe but reversib le myelosuppression was a common finding; adverse late sequelae were limite d to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintaine d their complete responses for 4+ to 39+ months (median, 15+ months), sugge sting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH. showing effective control land perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation. using stero ids and etoposide, with or without immunomodulatory agents. (C) 1999 by The American Society of Hematology.