Hematopoietic Stem Cell Transplantation for XIAP Deficiency in Japan
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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.
KeywordsHematopoietic 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
Inflammatory bowel disease
Hematopoietic stem cell transplantation
Nucleotide-binding oligomerization domain-containing protein 2
Reduced intensity conditioning
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).
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.
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