Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hematol. Nov 6, 2015; 4(4): 69-75
Published online Nov 6, 2015. doi: 10.5315/wjh.v4.i4.69
Treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis: Study protocol of a prospective pilot study
Shinsaku Imashuku
Shinsaku Imashuku, Department of Laboratory Medicine, Uji-Tokushukai Medical Center, Uji 611-0042, Japan
Author contributions: Imashuku S wrote a paper and designed a pilot study protocol.
Conflict-of-interest statement: The author states no conflict of interest and has received no payment in preparation of this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Shinsaku Imashuku, MD, PhD, Department of Laboratory Medicine, Uji-Tokushukai Medical Center, 145 Ishibashi, Makishima-cho, Uji 611-0042, Japan.
Telephone: +81-774-201111 Fax: +81-774-202336
Received: May 31, 2015
Peer-review started: June 4, 2015
First decision: August 14, 2015
Revised: September 6, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: November 6, 2015

In this manuscript, a number of debatable issues related to the diagnosis and treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH) will be addressed. Considering the heterogeneous nature of EBV-HLH, diagnostic efforts are required to clarify the precise nature of the disease at diagnosis, the number of EBV genome copies in peripheral blood, and localization of the EBV genome in lymphoid cells (B, T, or natural killer cells). Although the majority of cases of EBV-HLH develop without evidence of immunodeficiency, some cases have been found to be associated with chronic active EBV infection, genetic diseases such as X-linked lymphoproliferative disease (XLP, type 1, or type 2), or familial HLH (FHL, types 2-5). Due to such background heterogeneity, the therapeutic results of EBV-HLH have also been found to vary. Patients have been found to respond to corticosteroids alone or an etoposide-containing regimen, whereas other patients require hematopoietic stem cell transplantation. Thus, decision-making for optimal treatment of EBV-HLH and its eventual outcome requires evaluation in consideration of the precise nature of the disease. A protocol for a pilot study on the treatment of patients with EBV-HLH is presented here.

Keywords: Hemophagocytic lymphohistiocytosis, Epstein-Barr virus, Immune-chemotherapy, Rituximab, Hematopoietic stem cell transplantation

Core tip: Diagnosis of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH) must fulfill both the evidence of EBV infection and the diagnostic criteria for HLH. EBV-HLH is heterogeneous. The majority of EBV-HLH occurs in apparently immunocompetent subjects, but some are associated with chronic active EBV infection status, X-linked lymphoproliferative disease or with familial HLH. Thus, treatment and outcome differ significantly depending on the underlying disease. To find out a most appropriate treatment, various laboratory tests are required to clarify the underlying diseases.