J Korean Med Sci.  2005 Apr;20(2):209-214. 10.3346/jkms.2005.20.2.209.

Successful Treatment of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis with HLH-94 Protocol

• Lee JS
• Kang JH
• Lee GK
• Park HJ

• KMID: 1095191
• DOI: http://doi.org/10.3346/jkms.2005.20.2.209

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.

Keyword

Epstein-Barr Virus Infections; Hemophagocytic Lymphohistiocytosis; Histiocytosis, Non-Langer-hans-Cell; Etoposide; Cyclosporine; HLH-94; Child

MeSH Terms

Adolescent
Bone Marrow Transplantation
Child, Preschool
Cyclosporine/administration & dosage
Dexamethasone/administration & dosage
Drug Therapy, Combination
Epstein-Barr Virus Infections/*drug therapy
Etoposide/administration & dosage
Female
Histiocytosis, Non-Langerhans-Cell/*drug therapy
Humans
Male
Research Support, Non-U.S. Gov't

Figure

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  Fig. 1 Detection of EBV genomic DNA from bone marrow cells of patients with EBV-HLH by PCR (size of PCR product; 139 bp).

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  Fig. 2 EBER expression was identified in nuclei of bone marrow cells by mRNA in situ hybridization using specific EBERs cDNA oligonucleotide probe (A, ×200; B, ×400).

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  Fig. 3 The smear of bone marrow aspirate showed histiocyte (H) with phagocytosis of RBC (R), platelet (PL) and neutrophil (N) (Wright stain, ×1,000)

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