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Allogeneic Hematopoietic Cell Transplantation in Patients with Primary Immunodeficiencies in Korea: Eleven-Year Experience in a Single Center

Journal of Clinical Immunology volume 38, pages 757–766 (2018)Cite this article

A Correction to this article was published on 10 October 2018

This article has been updated

Abstract

Purpose

We aimed to report our single-center experience of allogeneic hematopoietic cell transplantation (HCT), which has been the only curative option for certain patients with lethal primary immunodeficiencies (PIDs).

Methods

We summarized the results of HCT performed for patients with PIDs for 11 consecutive years from 2006 to 2016 at Samsung Medical Center, Seoul, Korea. Twenty-six patients with PIDs received HCT. Most had chronic granulomatous disease (42.3%), Wiskott Aldrich syndrome (15.4%), or severe combined immunodeficiency (11.5%).

Results

Nine patients (34.6%) received HCT during the former half period and 17 patients (65.4%) during the latter half period. Donor types were categorized as: matched sibling donor (n = 5), unrelated donor (n = 17), and familial mismatched donor (FMMD) (n = 4). Unrelated HCT and FMMD transplantation were increasingly performed in the latter half period compared to the first (5 vs. 16, P = 0.034). Five patients experienced initial engraftment failure, but all of them were eventually engrafted after additional HCTs. The 3-year probability of overall survival was 72.0%. Seven patients (26.9%) died, and the causes of death were bacterial sepsis (n = 4), pneumonia (n = 1), chronic graft-versus-host disease (GVHD) (n = 1), and diffuse alveolar hemorrhage (n = 1). Two patients with bacterial sepsis and a patient with pneumonia also had chronic GVHD. Unrelated HCT and use of methotrexate were associated with poor outcome. Complete chimerism was attained in 85.0% at 1 year after HCT.

Conclusion

PID candidates have been increasingly identified for allogeneic HCT in Korea, and the majority of them could be cured by HCT. Establishment of a systematic registry of PID patients for HCT is needed.

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Change history

  • 10 October 2018

    The original version of this article unfortunately contained a mistake in the 7th author’s given name. The correct version is presented above.

Reference

  1. Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee report on inborn errors of immunity. J Clin Immunol. 2018;38:96–128.

    Article  Google Scholar 

  2. Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696–726.

    CAS  Article  Google Scholar 

  3. Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, et al. Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol. 2016;138:375–85.

    Article  Google Scholar 

  4. Son S, Kang J, Kim JM, Sung S, Kim Y, Lee H, et al. The first newborn screening study of T-cell receptor excision circle and к-deleting recombination excision circle for severe combined immunodeficiency in Korea: a pilot study. Pediatr Infect Vaccine. 2017;24:134–40.

    Article  Google Scholar 

  5. Gatti RA, Meuwissen HJ, Allen HD, Hong R, Good RA. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet. 1968;2:1366–9.

    CAS  Article  Google Scholar 

  6. Bach FH, Albertini RJ, Joo P, Anderson JL, Bortin MM. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Lancet. 1968;2:1364–6.

    CAS  Article  Google Scholar 

  7. Antoine C, Muller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. Lancet. 2003;361:553–60.

    Article  Google Scholar 

  8. Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126:602–10.e1–11.

    Article  Google Scholar 

  9. Pai SY, Cowan MJ. Stem cell transplantation for primary immunodeficiency diseases: the North American experience. Curr Opin Allergy Clin Immunol. 2014;14:521–6.

    CAS  Article  Google Scholar 

  10. Connelly JA. Hematopoietic stem cell transplant for a new primary immunodeficiency disorder: a voyage where no transplant physician has gone before. Biol Blood Marrow Transplant. 2017;23:863–4.

    Article  Google Scholar 

  11. 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.

    CAS  Google Scholar 

  12. Horwitz ME, Sullivan KM. Chronic graft-versus-host disease. Blood Rev. 2006;20:15–27.

    Article  Google Scholar 

  13. Baron F, Sandmaier BM. Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Leukemia. 2006;20:1690–700.

    CAS  Article  Google Scholar 

  14. Rousso SZ, Shamriz O, Zilkha A, Braun J, Averbuch D, Or R, et al. Hematopoietic stem cell transplantations for primary immune deficiencies: 3 decades of experience from a tertiary medical center. J Pediatr Hematol Oncol. 2015;37:e295–300.

    CAS  Article  Google Scholar 

  15. Morio T, Atsuta Y, Tomizawa D, Nagamura-Inoue T, Kato K, Ariga T, et al. Outcome of unrelated umbilical cord blood transplantation in 88 patients with primary immunodeficiency in Japan. Br J Haematol. 2011;154:363–72.

    Article  Google Scholar 

  16. Filipovich AH, Stone JV, Tomany SC, Ireland M, Kollman C, Pelz CJ, et al. Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Blood. 2001;97:1598–603.

    CAS  Article  Google Scholar 

  17. Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371:434–46.

    CAS  Article  Google Scholar 

  18. Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs HD, et al. Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980–2009: an international collaborative study. Blood. 2011;118:1675–84.

    CAS  Article  Google Scholar 

  19. Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986;314:729–35.

    CAS  Article  Google Scholar 

  20. Kharfan-Dabaja M, Mhaskar R, Reljic T, Pidala J, Perkins JB, Djulbegovic B, Kumar A. Mycophenolate mofetil versus methotrexate for prevention of graft-versus-host disease in people receiving allogeneic hematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2014;Cd010280.

  21. Fernandes JF, Rocha V, Labopin M, Neven B, Moshous D, Gennery AR, et al. Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? Blood. 2012;119:2949–55.

    CAS  Article  Google Scholar 

  22. Chang TY, Jaing TH, Lee WI, Chen SH, Yang CP, Hung IJ. Single-institution experience of unrelated cord blood transplantation for primary immunodeficiency. J Pediatr Hematol Oncol. 2015;37:e191–3.

    Article  Google Scholar 

  23. Frangoul H, Wang L, Harrell FE Jr, Manes B, Calder C, Domm J. Unrelated umbilical cord blood transplantation in children with immune deficiency: results of a multicenter study. Bone Marrow Transplant. 2010;45:283–8.

    CAS  Article  Google Scholar 

  24. Park M, Lee YH, Kang HR, Lee JW, Kang HJ, Park KD, et al. Unrelated donor cord blood transplantation for non-malignant disorders in children and adolescents. Pediatr Transplant. 2014;18:221–9.

    Article  Google Scholar 

  25. Farhadfar N, Hogan WJ. Overview of the progress on haploidentical hematopoietic transplantation. World J Transplant. 2016;6:665–74.

    Article  Google Scholar 

  26. Dvorak CC, Hassan A, Slatter MA, Honig M, Lankester AC, Buckley RH, et al. Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. J Allergy Clin Immunol. 2014;134:935–43 e15.

    Article  Google Scholar 

  27. Slatter MA, Gennery AR. Approaches to the removal of T-lymphocytes to minimize graft-versus-host disease in patients with primary immunodeficiencies who do not have a matched sibling donor. Curr Opin Allergy Clin Immunol. 2017;17:414–20.

    Article  Google Scholar 

  28. Rao K, Amrolia PJ, Jones A, Cale CM, Naik P, King D, et al. Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen. Blood. 2005;105:879–85.

    CAS  Article  Google Scholar 

  29. Gungor T, Teira P, Slatter M, Stussi G, Stepensky P, Moshous D, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383:436–48.

    CAS  Article  Google Scholar 

  30. Ouachee-Chardin M, Elie C, de Saint Basile G, Le Deist F, Mahlaoui N, Picard C, et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics. 2006;117:e743–50.

    Article  Google Scholar 

  31. Slatter MA, Rao K, Abd Hamid IJ, Nademi Z, Chiesa R, Elfeky R, et al. Treosulfan and fludarabine conditioning for hematopoietic stem cell transplantation in children with primary immunodeficiency: UK experience. Biol Blood Marrow Transplant. 2018;24:529–36.

    CAS  Article  Google Scholar 

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Author information

Affiliations

  1. Division of Hematology and Oncology, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Eun Sang Yi, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo & Keon Hee Yoo

  2. Department of Pediatrics, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea

    Eun Sang Yi

  3. Department of Pediatrics, Chungbuk National University Hospital, Cheongju, South Korea

    Young Bae Choi

  4. Department of Pediatrics, Cha Bundang Medical Centre, Cha University, Seongnam, South Korea

    Na Hee Lee

  5. Departments of laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Eun-Sook Kang

  6. Division of Pediatric Infectious Diseases and Immunodeficiency, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Yae-Jean Kim

  7. Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea

    Keon Hee Yoo

  8. Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea

    Keon Hee Yoo

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  1. Eun Sang Yi
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  2. Young Bae Choi
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Correspondence to Keon Hee Yoo.

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The authors declare that there are no conflicts of interest.

Ethical Standards

The study was approved by the Institutional Review Board of Samsung Medical Center and performed in accordance with the principles of the Declaration of Helsinki. The informed consent was waived.

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Yi, E.S., Choi, Y.B., Lee, N.H. et al. Allogeneic Hematopoietic Cell Transplantation in Patients with Primary Immunodeficiencies in Korea: Eleven-Year Experience in a Single Center. J Clin Immunol 38, 757–766 (2018). https://doi.org/10.1007/s10875-018-0542-7

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Keywords

  • Hematopoietic cell transplantation
  • bone marrow transplantation
  • primary immunodeficiency
  • child