Effective Control of Epstein-Barr Virus–Related Hemophagocytic Lymphohistiocytosis With Immunochemotherapy

• Published in: Blood 1999-03, Vol.93 (6), p.1869-1874
• Main Authors: Imashuku, Shinsaku, Hibi, Shigeyoshi, Ohara, Toshio, Iwai, Asayuki, Sako, Masahiro, Kato, Masahiko, Arakawa, Hirokazu, Sotomatsu, Manabu, Kataoka, Satoshi, Asami, Keiko, Hasegawa, Daijiro, Kosaka, Yoshiyuki, Sano, Kimihiko, Igarashi, Noboru, Maruhashi, Keiko, Ichimi, Ryouji, Kawasaki, Hajime, Maeda, Naoko, Tanizawa, Akihiko, Arai, Koji, Abe, Takanori, Hisakawa, Hiroaki, Miyashita, Hidemasa, Henter, Jan-Inge
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V93.6.1869.406a31_1869_1874

The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder. 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 criteria for this reactive disorder of the mononuclear phagocyte system. Treatment of life-threatening emergencies was left to the discretion of participating investigators and typically included either intravenous Ig or cyclosporin A (CSA). Five patients (29%) entered complete remission during the induction phase (1 to 2 months), whereas 10 others (57%) required additional treatment to achieve this status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone marrow transplantation. Severe but reversible myelosuppression was a common finding; adverse late sequelae were limited to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintained their complete responses for 4+ to 39+ months (median, 15+ months), suggesting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH, showing effective control (and perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation, using steroids and etoposide, with or without immunomodulatory agents.