Skip to main content

Advertisement

SpringerLink
Log in

Haploidentical Hematopoietic Stem Cell Transplantation for XIAP Deficiency: a Single-Center Report

  • Original Article
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Purpose

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in the XIAP/BIRC4 gene is a rare inherited primary immunodeficiency also known as X-linked lymphoproliferative syndrome type 2 (XLP2). Hematopoietic stem cell transplantation (HSCT) is currently the only curative strategy available. However, few studies of haploidentical HSCT have been published regarding the outcomes in patients with this syndrome.

Methods

We evaluated the XIAP gene analysis and clinical characteristics of four Chinese patients with XIAP who underwent haploidentical HSCT.

Results

The mutations in the two of four patients had not yet been reported in the literature. All of the patients had recurrent hemophagocytic lymphohistiocytosis but did not have a good matched donor and underwent haploidentical HSCT at BCH in China between September 2016 and December 2018. All four patients received antithymocyte globulin with fludarabine-based regimens. Two patients underwent reduced intensity conditioning (RIC), and the other two received modified myeloablative conditioning (MAC) regimens. Three of the four patients survived. Three patients experienced complications with mixed chimerism. One of the four patients who underwent RIC had early graft loss and then developed grade IV acute graft-versus-host disease (GVHD) after donor lymphocyte infusion with bone marrow. The two patients who received MAC survived with no or mild GVHD, even though one of them developed hepatic veno-occlusive disease in the early stage of transplantation.

Conclusions

Haploidentical HSCT may be a treatment option for patients with XIAP deficiency who lack a good matched donor. More studies are needed to determine whether modified MAC with reduced toxicity is more suitable for haploidentical transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Purtilo DT, Grierson HL. Methods of detection of new families with X-linked lymphoproliferative disease. Cancer Genet Cytogenet. 1991;51(2):143–53.

    Article  CAS  Google Scholar 

  2. Sumegi J, Huang D, Lanyi A, Davis JD, Seemayer TA, Maeda A, et al. Correlation of mutations of the SH2D1A gene and Epstein–Barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease. Blood. 2000;96:3118–25.

    PubMed  CAS  Google Scholar 

  3. Xi Y, Hirokazu K, Naonori N, Toshihiko I, Kazuko H, Ritsuko M, et al. Clinical and genetic characteristics of XIAP deficiency in Japan. J Clin Immunol. 2012;32:411–20.

    Article  CAS  Google Scholar 

  4. Eckelman BP, Salvesen GS, Scott FL. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep. 2006;7:988–94.

    Article  CAS  Google Scholar 

  5. Rezaei N, Mahmoudi E, Aghamohammadi A, Das R, Nichols KE. X-linked lymph.oproliferative syndrome: a genetic condition typified by the triad of infection, immunodeficiency and lymphoma. Br J Haematol. 2011;152:13–30.

    Article  CAS  Google Scholar 

  6. Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, et al. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011;13:255–62.

    Article  Google Scholar 

  7. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491:119–24.

    Article  CAS  Google Scholar 

  8. Marsh RA, Rao K, Satwani P, Lehmberg K, Müller I, Li D, et al. Allogeneic hematopoietic cell transplantation for XIAP deficiency:an international survey reveals poor outcomes. Blood. 2013;121:877–83.

    Article  CAS  Google Scholar 

  9. Ono S, Okano T, Hoshino A, Yanagimachi M, Hamamoto K, Nakazawa Y, et al. Hematopoietic stem cell transplantation for XIAP deficiency in Japan. J Clin Immunol. 2017;37(1):85–91.

    Article  CAS  Google Scholar 

  10. O'Rafferty C, Velangi M, Lawson S, Hiwarkar P, Motwani J. IFNɣ block, treosulfan conditioning and αβ T cell deplete PBSCT for XIAP-deficient HLH. J Clin Immunol. 2017;37(6):511–3.

    Article  Google Scholar 

  11. Jiang MY, Guo X, Sun SW, Li Q, Zhu YP. Successful allogeneic hematopoietic stem cell transplantation in a boy with X-linked inhibitor of apoptosis deficiency presenting with hemophagocytic lymphohistiocytosis: a case report. Exp Ther Med. 2016;12(3):1341–4.

    Article  Google Scholar 

  12. Chenguang J, Bin W, Guanghua Z, Rui Z, Kai W, Yan Y, et al. Haploidentical hematopoietic stem cell transplantation using reduced-intensity conditioning for pediatric patients with familial hemophagocytic lymphohistiocytosis. Pediatr Invest. 2018;2(4):216–21.

    Article  Google Scholar 

  13. Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohis -tiocytosis. Pediatr Blood Cancer. 2007;48:124–31.

    Article  Google Scholar 

  14. Bergsten E, Horne A, Aricó M, Astigarraga I, Egeler RM, Filipovich AH, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728–38.

    Article  CAS  Google Scholar 

  15. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15(3):367–9.

    Article  Google Scholar 

  16. Hamidieh AA, Pourpak Z, Hosseinzadeh M, Fazlollahi MR, Alimoghaddam K, Movahedi M, et al. Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism. Bone Marrow Transplant. 2012;47:646–50.

    Article  CAS  Google Scholar 

  17. Olsson RF, Logan BR, Chaudhury S, Zhu X, Akpek G, Bolwell BJ, et al. Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia. 2015;29(8):1754–62.

    Article  CAS  Google Scholar 

  18. Leischhauer K, Locatelli F, Zecca M, Orofino MG, Giardini C, De Stefano P, et al. Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus graft direction. Blood. 2006;107:2984–92.

    Article  CAS  Google Scholar 

  19. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

    PubMed  CAS  Google Scholar 

  20. Martin PJ, Lee SJ, Przepiorka D, Horowitz MM, Koreth J, Vogelsang GB, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: VI. The 2014 Clinical Trial Design Working Group Report. Biol Blood Marrow Transplant. 2015;21(8):1343–59.

    Article  Google Scholar 

  21. Horn PC, Belohradsky BH, Urban C, Weber-Mzell D, Meindl A, Schuster V. Two new families with Xlinked inhibitor of apoptosis deficiency and a review of all 26 published cases. J Allergy Clin Immunol. 2011;127:544–6.

    Article  Google Scholar 

  22. LaCasse EC, Baird S, Korneluk RG, MacKenzie AE. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene. 1998;17:3247–59.

    Article  Google Scholar 

  23. Beug ST, Cheung HH, LaCasse EC, Korneluk RG. Modulation of immune signalling by inhibitors of apoptosis. Trends Immunol. 2012;33:535–45.

    Article  CAS  Google Scholar 

  24. Pedersen J, LaCasse EC, Seidelin JB, Coskun M, Nielsen OH. Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation. Trends Mol Med. 2014;20:652–65.

    Article  CAS  Google Scholar 

  25. Janin K, Lisanne MS, Stefanie R, Ramona R, Lazaros V, Monica Y, et al. TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP. Cell Death Dis. 2019;10(10):700.

    Article  CAS  Google Scholar 

  26. LaCasse EC. Pulling the plug on a cancer cell by eliminating XIAP with AEG35156. Cancer Lett. 2013;332:215–24.

    Article  CAS  Google Scholar 

  27. Ammann S, Elling R, Gyrd-Hansen M, Dückers G, Bredius R, Burns SO, et al. A new functional assay for the diagnosis of X-linked inhibitor of apoptosis (XIAP) deficiency. Clin Exp Immunol. 2014;176(3):394–400.

    Article  CAS  Google Scholar 

  28. Aguilar C, Lenoir C, Lambert N, Bègue B, Brousse N, Canioni D, et al. Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient male patients and female symptomatic carriers. J Allergy Clin Immunol. 2014;134:1131–41.

    Article  CAS  Google Scholar 

  29. Dziadzio M, Ammann S, Canning C, Boyle F, Hassan A, Cale C, et al. Symptomatic males and female carriers in a large Caucasian kindred with XIAP deficiency. J Clin Immunol. 2015;35(5):439–44.

    Article  CAS  Google Scholar 

  30. Aguilar C, Latour S. X-linked inhibitor of apoptosis protein deficiency: more than an X-linked lymphoproliferative syndrome. J Clin Immunol. 2015;35:331–8.

    Article  CAS  Google Scholar 

  31. Eucario LR, Monica MRF, Sandra IPA. Reduced BUCY 2 and G-CSF-primed bone marrow associateswith low graft-versus-host-disease and transplant-relatedmortality in allogeneic HSCT. Ann Hematol. 2017;96(9):1525–31.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Grant (No. ZY201404), and Beijing Municipal Administration of Hospitals DengFeng Program (No. DFL20151101), and National Science and Technology Key Projects (No. 2017ZX09304029004).

Author information

Authors and Affiliations

  1. Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, P.R., China

    Jun Yang, Guang-Hua Zhu, Bin Wang, Rui Zhang, Chen-Guang Jia, Yan Yan, Hong-Hao Ma & Mao-Quan Qin

  2. National Key Discipline of Pediatrics, Capital Medical University, Beijing, China

    Jun Yang, Guang-Hua Zhu, Bin Wang, Rui Zhang, Chen-Guang Jia, Yan Yan, Hong-Hao Ma & Mao-Quan Qin

  3. Key Laboratory of Major Diseases in Children, Ministry of Education, Capital Medical University, 56 Nanlishi Road, Beijing, China

    Jun Yang, Guang-Hua Zhu, Bin Wang, Rui Zhang, Chen-Guang Jia, Yan Yan, Hong-Hao Ma & Mao-Quan Qin

  4. Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 56 Nanlishi Road, Beijing, China

    Jun Yang, Guang-Hua Zhu, Bin Wang, Rui Zhang, Chen-Guang Jia, Yan Yan, Hong-Hao Ma & Mao-Quan Qin

Authors
  1. Jun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guang-Hua Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chen-Guang Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hong-Hao Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mao-Quan Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mao-Quan Qin.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, J., Zhu, GH., Wang, B. et al. Haploidentical Hematopoietic Stem Cell Transplantation for XIAP Deficiency: a Single-Center Report. J Clin Immunol 40, 893–900 (2020). https://doi.org/10.1007/s10875-020-00795-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-020-00795-6

Keywords

Search

Navigation