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Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu–Yamaguchi Children’s Cancer Study Group

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Abstract

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu–Yamaguchi Children’s Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.

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Acknowledgments

We are grateful to Dr. Hiroyuki Komatsu for his help with the statistical analysis and Ms. Megumi Obara for her technical assistance. We also thank Mr. Youichi Ogata and Drs. Kaede Yanagita, Akinobu Matsuzaki, So-ichi Suenobu, Kozo Nagai and Shuichi Ozono for their useful comments on the manuscript.

Conflicts of interest

The authors declare that they have no conflicts of interest in association with this study.

Author information

Authors and Affiliations

  1. The Kyushu–Yamaguchi Children’s Cancer Study Group (KYCCSG), Kyushu, Japan

    Hiroshi Moritake, Sachiyo Kamimura, Hiroyuki Nunoi, Hideki Nakayama, Aiko Suminoe, Hiroko Inada, Jiro Inagaki, Fumio Yanai, Yasuhiro Okamoto, Yuichi Shinkoda, Maiko Shimomura, Nobuyoshi Itonaga, Noriko Hotta, Yasufumi Hidaka, Jun Okamura & Yoshifumi Kawano

  2. Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan

    Hiroshi Moritake, Sachiyo Kamimura & Hiroyuki Nunoi

  3. Department of Pediatrics, National Hospital Organization, Fukuoka-Higashi Medical Center, Fukuoka, Japan

    Hideki Nakayama

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

    Aiko Suminoe

  5. Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan

    Hiroko Inada

  6. Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    Jiro Inagaki & Jun Okamura

  7. Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka, Japan

    Fumio Yanai

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

    Yasuhiro Okamoto & Yoshifumi Kawano

  9. Department of Pediatrics, Kagoshima City Hospital, Kagoshima, Japan

    Yuichi Shinkoda

  10. Department of Pediatrics, Yamaguchi University, Yamaguchi, Japan

    Maiko Shimomura

  11. Department of Pediatrics, Oita Prefectural Hospital, Oita, Japan

    Nobuyoshi Itonaga

  12. Department of Pediatrics, Tokuyama Central Hospital, Tokuyama, Japan

    Noriko Hotta

  13. Department of Pediatrics, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

    Yasufumi Hidaka

  14. Department of Human Genome Research, Kazusa DNA Research Institute, Kisarazu, Japan

    Osamu Ohara

  15. Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Japan

    Masakatsu Yanagimachi

  16. Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan

    Noriko Nakajima

Authors
  1. Hiroshi Moritake
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  2. Sachiyo Kamimura
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  13. Noriko Hotta
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  14. Yasufumi Hidaka
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  15. Osamu Ohara
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  16. Masakatsu Yanagimachi
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  17. Noriko Nakajima
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  18. Jun Okamura
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  19. Yoshifumi Kawano
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Corresponding author

Correspondence to Hiroshi Moritake.

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Moritake, H., Kamimura, S., Nunoi, H. et al. Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu–Yamaguchi Children’s Cancer Study Group. Int J Hematol 100, 70–78 (2014). https://doi.org/10.1007/s12185-014-1591-1

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  • DOI: https://doi.org/10.1007/s12185-014-1591-1

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