Journal of Clinical Immunology

, Volume 37, Issue 1, pp 85–91 | Cite as

Hematopoietic Stem Cell Transplantation for XIAP Deficiency in Japan

  • Shintaro Ono
  • Tsubasa Okano
  • Akihiro Hoshino
  • Masakatsu Yanagimachi
  • Kazuko Hamamoto
  • Yozo Nakazawa
  • Toshihiko Imamura
  • Masaei Onuma
  • Hidetaka Niizuma
  • Yoji Sasahara
  • Hiroshi Tsujimoto
  • Taizo Wada
  • Reiko Kunisaki
  • Masatoshi Takagi
  • Kohsuke Imai
  • Tomohiro Morio
  • Hirokazu KaneganeEmail author
Original Article



X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare immunodeficiency that is characterized by recurrent hemophagocytic lymphohistiocytosis (HLH) and splenomegaly and sometimes associated with refractory inflammatory bowel disease (IBD). Although hematopoietic stem cell transplantation (HSCT) is the only curative therapy, the outcomes of HSCT for XIAP deficiency remain unsatisfactory compared with those for SLAM-associated protein deficiency and familial HLH.


To investigate the outcomes and adverse events of HSCT for patients with XIAP deficiency, a national survey was conducted.


A spreadsheet questionnaire was sent to physicians who had provided HSCT treatment for patients with XIAP deficiency in Japan.


Up to the end of September 2016, 10 patients with XIAP deficiency had undergone HSCT in Japan, 9 of whom (90%) had survived. All surviving patients had received a fludarabine-based reduced intensity conditioning (RIC) regimen. Although 5 patients developed post-HSCT HLH, 4 of them survived after etoposide administration. In addition, the IBD associated with XIAP deficiency improved remarkably after HSCT in all affected cases.


The RIC regimen and HLH control might be important factors for successful HSCT outcomes, with improved IBD, in patients with XIAP deficiency.


Hematopoietic stem cell transplantation hemophagocytic lymphohistiocytosis inflammatory bowel disease reduced intensity conditioning XIAP deficiency X-linked lymphoproliferative syndrome 



Absolute neutrophil count


Baculoviral IAP repeat-containing protein 4


Bone marrow


Cord blood




Dexamethasone palmitate


Epstein-Barr virus


Graft-versus-host disease


Inflammatory bowel disease


Hemophagocytic lymphohistiocytosis


Hematopoietic stem cell transplantation


Myeloablative conditioning


Nucleotide-binding oligomerization domain-containing protein 2


Reduced intensity conditioning


SLAM-associated protein


Total body irradiation


Total lymphoid irradiation


X-linked inhibitor of apoptosis protein


X-linked lymphoproliferative syndrome



This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to H.K.) and the Ministry of Health, Labour, and Welfare of Japan (to T.M).

Authorship Contribution

S.O. and H.K. wrote the manuscript. T.O., A.H., and T.W. performed the immunological and genetic studies. S.O., M.Y., K.H., Y.N., T.I., M.O., H.N., Y.S., and H.T. collected the data. R.K. performed the colonoscopies. M.T., K.I., and T.M. contributed critical discussion. H.K. designed the study.

Compliance with Ethical Standards

Conflicts of Interest

The authors have no conflicts of interest to disclose.

Supplementary material

10875_2016_348_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 21 kb)
10875_2016_348_MOESM2_ESM.docx (77 kb)
ESM 2 (DOCX 76 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shintaro Ono
    • 1
  • Tsubasa Okano
    • 1
  • Akihiro Hoshino
    • 1
  • Masakatsu Yanagimachi
    • 1
    • 2
  • Kazuko Hamamoto
    • 3
  • Yozo Nakazawa
    • 4
  • Toshihiko Imamura
    • 5
  • Masaei Onuma
    • 6
  • Hidetaka Niizuma
    • 7
  • Yoji Sasahara
    • 7
  • Hiroshi Tsujimoto
    • 8
  • Taizo Wada
    • 9
  • Reiko Kunisaki
    • 10
  • Masatoshi Takagi
    • 11
  • Kohsuke Imai
    • 11
  • Tomohiro Morio
    • 1
  • Hirokazu Kanegane
    • 1
    Email author
  1. 1.Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Department of PediatricsYokohama City University Graduate School of MedicineYokohamaJapan
  3. 3.Department of PediatricsHiroshima Red Cross HospitalHiroshimaJapan
  4. 4.Department of PediatricsShinshu University School of MedicineMatsumotoJapan
  5. 5.Department of PediatricsKyoto Prefectural University of Medicine, Graduate School of Medical ScienceKyotoJapan
  6. 6.Department of Hematology and OncologyMiyagi Children’s HospitalSendaiJapan
  7. 7.Department of PediatricsTohoku University School of MedicineSendaiJapan
  8. 8.Department of PediatricsWakayama Medical UniversityWakayamaJapan
  9. 9.Department of Pediatrics, Institute of Medical, Pharmaceutical and Health Sciences, School of MedicineKanazawa UniversityKanazawaJapan
  10. 10.Inflammatory Bowel Disease CentreYokohama City University Medical CentreYokohamaJapan
  11. 11.Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan

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