Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Pediatric Transplants

Long-term outcome of non-ablative booster BMT in patients with SCID

Bone Marrow Transplantation volume 48, pages 1050–1055 (2013)Cite this article

Subjects

Abstract

SCID is a fatal syndrome caused by mutations in at least 13 different genes. It is characterized by the absence of T cells. Immune reconstitution can be achieved through nonablative related donor BMT. However, the first transplant may not provide sufficient immunity. In these cases, booster transplants may be helpful. A prospective/retrospective study was conducted of 49 SCID patients (28.7% of 171 SCIDs transplanted over 30 years) who had received booster transplants to define the long-term outcome, factors contributing to a need for a booster and factors that predicted success. Of the 49 patients, 31 (63%) are alive for up to 28 years. Age at initial transplantation was found to have a significant effect on outcome (mean of 194 days old for patients currently alive, versus a mean of 273 days old for those now deceased, P=0.0401). Persistent viral infection was present in most deceased booster patients. In several patients, the use of two parents as sequential donors resulted in striking T-and B-cell immune reconstitution. A majority of the patients alive today have normal or adequate T-cell function and are healthy. Nonablative booster BMT can be lifesaving for SCID.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Buckley RH . Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol 2004; 22: 625–655.

    Article  CAS  PubMed  Google Scholar 

  2. Buckley RH . Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Immunol Res 2011; 49: 25–43.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL et al. Hematopoietic stem cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 1999; 340: 508–516.

    Article  CAS  PubMed  Google Scholar 

  4. Myers LA, Patel DD, Puck JM, Buckley RH . Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood 2002; 99: 872–878.

    Article  CAS  PubMed  Google Scholar 

  5. Kline RM, Stiehm ER, Cowan MJ . Bone marrow ‘boosts’ following T cell depleted haploidentical bone marrow transplantation. Bone Marrow Transplant 1996; 17: 543–548.

    CAS  PubMed  Google Scholar 

  6. Remberger M, Ringden O, Ljungman P, Hagglund H, Winiarski J, Lonnqvist B et al. Booster marrow or blood cells for graft failure after allogeneic bone marrow transplantation. Bone Marrow Transplant 1998; 22: 73–78.

    Article  CAS  PubMed  Google Scholar 

  7. Min CK, Kim DW, Lee JW, Min WS, Kim CC . Additional stem cell therapy for graft failure after allogeneic bone marrow transplantation. Acta Haematol 2000; 104: 185–192.

    Article  CAS  PubMed  Google Scholar 

  8. Wolff SN . Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation. Bone Marrow Transplant 2002; 29: 545–552.

    Article  CAS  PubMed  Google Scholar 

  9. Slatter MA, Bhattacharya A, Abinun M, Flood TJ, Cant AJ, Gennery AR . Outcome of boost haemopoietic stem cell transplant for decreased donor chimerism or graft dysfunction in primary immunodeficiency. Bone Marrow Transplant 2005; 35: 683–689.

    Article  CAS  PubMed  Google Scholar 

  10. Booth C, Ribeil JA, Audat F, Dal Cortivo L, Veys PA, Thrasher AJ et al. CD34 stem cell top-ups without conditioning after initial haematopoietic stem cell transplantation for correction of incomplete haematopoietic and immunological recovery in severe congenital immunodeficiencies. Br J Haematol 2006; 135: 533–537.

    Article  PubMed  Google Scholar 

  11. Al-Herz W, Bousfiha A, Casanova J-L, Chapel H, Conley ME, Cunningham-Rundles C et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Frontiers in Immunology 2011; 2: 54.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Chinen J, Davis J, De Ravin SS, Hay BN, Hsu AP, Linton GF et al. Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency. Blood 2007; 110: 67–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Buckley RH, Dees SC, O'Fallon WM . Serum immunoglobulins I. levels in normal children and in uncomplicated childhood allergy. Pediatr 1968; 41: 600–611.

    CAS  Google Scholar 

  14. Buckley RH, Dees SC . Serum immunoglobulins. III. Abnormalities associated with chronic urticaria in children. J. Allergy 1967; 40: 294–303.

    Article  CAS  PubMed  Google Scholar 

  15. Buckley RH, Schiff SE, Sampson HA, Schiff RI, Markert ML, Knutsen AP et al. Development of immunity in human severe primary T cell deficiency following haploidentical bone marrow stem cell transplantation. J Immunol 1986; 136: 2398–2407.

    CAS  PubMed  Google Scholar 

  16. Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Cunningham-Rundles S, Dupont B et al. Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 1983; 61: 341–348.

    CAS  PubMed  Google Scholar 

  17. Schiff SE, Kurtzberg J, Buckley RH . Studies of human bone marrow treated with soybean lectin and sheep erythrocytes: stepwise analysis of cell morphology, phenotype and function. Clin Exp Immunol 1987; 68: 685–693.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Railey MD, LoKhnygina Y, Buckley RH . Long term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pre-transplant chemotherapy or post-transplant GVHD prophylaxis. J Pediatr 2009; 155: 834–840.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Haddad E, Deist FL, Aucouturier P, Cavazzana-Calvo M, Blanche S, Basile GD et al. Long-term chimerism and B-cell function after bone marrow transplantation in patients with severe combined immunodeficiency with B cells: a single-center study of 22 patients. Blood 1999; 94: 2923–2930.

    CAS  PubMed  Google Scholar 

  20. Buckley RH . B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review. J Allergy Clin Immunol 2010; 125: 790–797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Buckley RH, Win CM, Moser BK, Parrott RE, Sajaroff E, Sarzotti-Kelsoe M . Post-transplantation B cell function in different molecular types of SCID. J Clin Immunol 2013; 33: 96–110.

    Article  CAS  PubMed  Google Scholar 

  22. Palmer K, Green TD, Roberts JL, Sajaroff E, Cooney M, Parrott R et al. Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency. J Allergy Clin Immunol 2007; 120: 423–428.

    Article  CAS  PubMed  Google Scholar 

  23. Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB . Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol 2012; 30: 1080–1086.

    Article  PubMed  Google Scholar 

  24. Titman P, Pink E, Skucek E, O'Hanlon K, Cole TJ, Gaspar J et al. Cognitive and behavioural abnormalities in children following haematopoietic stem cell transplantation for severe congenital immunodeficiencies. Blood 2008; 112: 3907–3913.

    Article  CAS  PubMed  Google Scholar 

  25. Sanders JE, the Seattle Marrow Transplant Group. Effects of bone marrow transplantation on reproductive function. Late Effects of Treatment for Childhood Cancer. Wiley-Liss Publishing Ltd: New York, NY, 1992 pp 95–101.

    Google Scholar 

  26. Buckley RH . The long quest for neonatal screening for severe combined immunodeficiency. J Allergy Clin Immunol 2012; 129: 597–604.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hassan A, Booth C, Brightwell A, Allwood Z, Veys P, Rao K et al. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency. Blood 2012; 120: 3615–3624.

    Article  CAS  PubMed  Google Scholar 

  28. Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med 2009; 360: 447–458.

    Article  CAS  PubMed  Google Scholar 

  29. Sideri A, Neokleous N, De La Grange PB, Guerton B, Le Bousse Kerdilles MC, Uzan G et al. An overview of the progress on double umbilical cord blood transplantation. Haematologica 2011; 96: 1213–1220.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH Grants AI047605 and AI042951 and by a Dean’s Research Fellowship to CLT from Duke University.

Author information

Authors and Affiliations

  1. Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC, USA

    C L Teigland, R E Parrott & R H Buckley

Authors
  1. C L Teigland
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R E Parrott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R H Buckley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R H Buckley.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Teigland, C., Parrott, R. & Buckley, R. Long-term outcome of non-ablative booster BMT in patients with SCID. Bone Marrow Transplant 48, 1050–1055 (2013). https://doi.org/10.1038/bmt.2013.6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2013.6

Keywords

This article is cited by

Search

Advanced search

Quick links