International Journal of Hematology

DOI: 10.1007/s12185-019-02612-2 Pages: 612-617

Factors predicting the recurrence of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children after treatment using the HLH-2004 protocol

1. Shinshu University Hospital, Division of Blood Transfusion

2. Shinshu University School of Medicine, Department of Pediatrics

3. National Hospital Organization Nagoya Medical Center, Clinical Research Center

4. Shinshu University, Department of Clinical Laboratory Sciences, School of Health Sciences

5. Kyushu University, Department of Pediatrics, Graduate School of Medical Sciences

6. Tokyo Medical and Dental University, Department of Child Health and Development, Graduate School of Medical and Dental Sciences

7. Jichi Medical University School of Medicine, Department of Pediatrics

8. Kagoshima University Graduate School of Medical and Dental Sciences, Department of Pediatrics

9. Toho University, Department of Pediatrics

10. Dokkyo Medical University, Department of Pediatrics

11. Gunma Children’s Medical Center, Department of Pediatrics

12. University of Toyama, Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences

13. Ehime University Graduate School of Medicine, Department of Pediatrics

Correspondence to:
Yozo Nakazawa
Tel: +81-263-37-2642



Epstein–Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is highly prevalent in Japan. To date, no standard treatment for EBV–HLH has been established owing to the diversity in treatment response and the difficulty in assessing prognostic factors. The present prospective study recruited 27 children with EBV–HLH who were also part of the HLH-2004 study. EBV load in the peripheral blood was monitored at diagnosis and 2, 4, and 8 weeks after treatment initiation. Additionally, T-cell receptor (TCR) clonality and other laboratory data were evaluated. TCR clonality was positive in 14 patients at diagnosis. Seven of 27 patients experienced recurrences after treatment. No correlation was noted among any clinical data at diagnosis of patients with and without recurrence. However, the recurrence rate was significantly higher in patients aged < 2 years and/or those with a high plasma EBV load of > 103 copies/mL 2 weeks after treatment than that in patients without these factors. These findings suggest that a younger age or a high EBV load in plasma at the early phase of treatment is a factor predicting a recurrence and helps guide the intensity of subsequent treatment phases for children with EBV–HLH.

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