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

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A Correction to this article was published on 11 April 2019

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Abstract

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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Change history

  • 11 April 2019

    The correct name of the first author should be ‘‘Ryu Yanagisawa’’, and not ‘‘Ryu Yanagaisawa’’ as given in the original publication of the article.

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Acknowledgements

This work was supported by a Grant-in-Aid for Clinical Cancer Research from the Ministry of Health, Labour and Welfare of Japan (H20-GanRinsho-Ippan-017), by the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED_16ek0109055h0003 and AMED_18ck0106462h0001), and by the Japan Leukemia Research Fund. The authors would like to thank Yūka Miyajima for assistance with preparation of the manuscript as well as secretarial assistance. The authors also thank Enago (http://www.enago.jp) for the English language review.

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Author notes

  1. Ryu Yanagaisawa and Kazuyuki Matsuda contributed equally to this work.

Authors and Affiliations

  1. Division of Blood Transfusion, Shinshu University Hospital, Matsumoto, Japan

    Ryu Yanagaisawa

  2. Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan

    Ryu Yanagaisawa & Yozo Nakazawa

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

    Ryu Yanagaisawa, Akiko M. Saito & Keizo Horibe

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

    Kazuyuki Matsuda

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

    Shouichi Ohga

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

    Hirokazu Kanegane

  7. Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan

    Akira Morimoto

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

    Yasuhiro Okamoto

  9. Department of Pediatrics, Toho University, Tokyo, Japan

    Akira Ohara

  10. Department of Pediatrics, Dokkyo Medical University, Shimotsuga, Mibu, Japan

    Keitaro Fukushima

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

    Manabu Sotomatsu

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

    Keiko Nomura

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

    Eiichi Ishii

Authors
  1. Ryu Yanagaisawa
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  2. Kazuyuki Matsuda
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  6. Yasuhiro Okamoto
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  7. Akira Ohara
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  8. Keitaro Fukushima
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  10. Keiko Nomura
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  11. Akiko M. Saito
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  12. Keizo Horibe
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  13. Eiichi Ishii
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  14. Yozo Nakazawa
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Corresponding author

Correspondence to Yozo Nakazawa.

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Yanagaisawa, R., Matsuda, K., Ohga, S. et al. Factors predicting the recurrence of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children after treatment using the HLH-2004 protocol. Int J Hematol 109, 612–617 (2019). https://doi.org/10.1007/s12185-019-02612-2

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  • DOI: https://doi.org/10.1007/s12185-019-02612-2

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