Advances in the management of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a prototype of the hemophagocyt ic syndrome and occurs most often in children. Progress in cytokine researc h has now made it possible to show that HLH occurs as a consequence of unco ntrolled, dysregulated cellular immune reactivity caused by a number of dif ferent underlying diseases. Three major risk groups of HLH can be identifie d: (1) familial HLH (FHL), (2) Epstein-Barr virus-associated HLH (EBV-HLH), and (3) life-threatening infection-associated or underlying disease-unknow n HLH in infancy. Diagnostic criteria now exist that allow the differential diagnosis of these groups, which is important because distinct therapeutic measures are advised for each group. FHL patients require immediate applic ation of immunochemotherapy with a core combination of corticosteroids and etoposide together with monitoring of central nervous system disease by ear ly and repealed magnetic resonance imaging of the brain, followed by timely stem cell transplantation (SCT). EBV-HLH should also be treated with a com bination of corticosteroids and etoposide. Aggressive or relapsed cases sho uld be treated with cyclosporin A and, if necessary, with more intensive ch emotherapy, such as that used for non-Hodgkin's lymphoma. SCT may also be n eeded in these refractory cases. In cases of herpes simplex virus, adenovir us 7, and other pathogen-undetermined HLH in early infancy, it is of great importance to administer appropriate antiviral or antibacterial agents. The most important point to make regarding HLH treatment is that the underlyin g cause of HLH must be promptly established to enable the rapid application of the appropriate therapy. Currently, 30% to 40% of HLH cases have a poor outcome. It is necessary for hematologists to cooperate with specialists i n other fields so that early diagnosis, which is critical for improvements in outcome, can be made. Int J Hematol. 2000;72:1-11. (C) 2000 The Japanese Society of Hematology.