Immunomodulation treatment for childhood virus-associated haemophagocytic lymphohistiocytosis

Abstract

The Epstein-Barr virus (EBV), or human herpesvirus-6 (HHV-6) associated haemophagocytic lymphohistiocytosis, has been found prevalent in Taiwan; it affects previously healthy children and is always fatal when treated only supportively. Recognition of the underlying pathogenesis for this disease prompted adoption of an immunomodulatory regimen of intravenous immunoglobulin (IVIG) and/or etoposide on 17 such patients treated between 1990 and 1993. Remarkable improvement in patients' prognoses was demonstrated. Eight patients are still alive with a median follow-up of 1 year and 2 months post-treatment. Both IVIG and etoposide had positive immunomodulation effects such as alleviation of fever and normalization of haematological and hepatic parameters. Sustained complete response was obtained in two of nine cases of EBV-associated diseases treated with IVIG only. EBV transcripts become undetectable after etoposide and/or IVIG treatment without antiviral agents. Etoposide given by split-dose schedule appeared to be superior to conventional three-consecutive-days schedule for both remission induction and disease-free survival. Our preliminary trial apparently provides a promising improvement in the treatment of this previously fatal disease. IVIG or etoposide is effective in reversing the process of lymphohistiocytic dysregulation resulting from virus infection of immune cells in this syndrome and probably helps hosts to control active virus replication in certain cases, through immunomodulation.