title: Successful treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with HLH-94 protocol.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a rare, fatal disorder of children, affecting predominantly the mononuclear phagocytic system. Previous reports indicate that Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) can also be fatal in many cases, although the prognosis for EBV-HLH is better than for the familial form of hemophagocytic lymphohistiocytosis. We treated four patients with EBV-HLH using immunochemotherapy including steroid, etoposide (VP-16), and cyclosporin, according to the HLH-94 protocol. All patients experienced persistent fever, cytopenia, and hypertriglyceridemia. Serological testing for EBV showed reactivated EBV infections in all patients. EBV DNA detected by PCR and EBV-encoded small RNA measured by in situ hybridization were confirmed in the patients' bone marrow specimens. Hemophagocytosis was shown in bone marrow aspirates and liver biopsy specimen. Complete remission was achieved in all patients after induction and continuation therapy for 4-10 months (median, 7 months) and was maintained for 15-27 months (median, 19 months) without the need for bone marrow transplantation. These results suggest that EBV-HLH can be effectively controlled by immunochemotherapy using the HLH-94 protocol.
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju 361-711, Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Jin-Han
authors.initials: JH
authors.lastname: Kang
authors.forename: Geon-Kook
authors.initials: GK
authors.lastname: Lee
authors.forename: Hyeon-Jin
authors.initials: HJ
authors.lastname: Park
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000188:drug therapy*; D006801:Humans; D008297:Male
chemical_list: D005047:Etoposide; D003907:Dexamethasone; D016572:Cyclosporine