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:

Allografting

Matched unrelated bone marrow transplant for T+ combined immunodeficiency

Bone Marrow Transplantation volume 41, pages 947–952 (2008)Cite this article

Abstract

Little information is currently available on the outcome and the long-term restoration of immune function in infants with combined immunodeficiency and residual T cells (T+ CID) treated by BMT. We prospectively followed patients with T+ CID who received matched unrelated donor BMT at our center. Engraftment, immune reconstitution and transplant-related complications were recorded. Humoral and cellular immunity were evaluated. Ten patients with combined immune deficiency who had more than 1000 circulating T cells/μl were designated as having T+ CID. They were diagnosed at a mean age of 9.7 months and received a matched unrelated donor BMT at the mean age of 17.4 months. All 10 patients are alive and well at a mean of 110 months after transplant. All patients have evidence of full hemopoietic engraftment and robust immune function. We have shown here that matched unrelated donor BMT is highly effective in curing patients with T+ CID. This mode of treatment should be preferred for patients with T+ CID when a related identical donor is not available.

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

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  Google Scholar 

  2. Haddad E, Landais P, Friedrich W, Gerritsen B, Cavazzana-Calvo M, Morgan G et al. Long-term immune reconstitution and outcome after HLA-nonidentical T-cell depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients. Blood 1998; 91: 3646–3653.

    CAS  PubMed  Google Scholar 

  3. 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; 33: 1089–1095.

    Google Scholar 

  4. Caillat-Zucman S, Le Deist F, Haddad E, Gannagé M, Dal Cortivo L, Jabado N et al. Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-centre comparative analysis of genoidentical, haploidentical or unrelated donors. Bone Marrow Transplant 2004; 33: 1089–1095.

    Article  CAS  Google Scholar 

  5. Ball LM, Lankester AC, Bredius RG, Fibbe WE, van Tol MJ, Egeler RM . Graft dysfunction and delayed immune reconstitution following haploidentical peripheral blood hematopoietic stem cell transplantation. Bone Marrow Transplant 2005; 35 (Suppl 1): S35–S38.

    Article  Google Scholar 

  6. Patel DD, Gooding ME, Parrott RE, Curtis KM, Haynes BF, Buckley RH . Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 2000; 342: 1325–1332.

    Article  CAS  Google Scholar 

  7. Notarangelo LD, Giliani S, Mazza C, Mella P, Savoldi G, Rodriguez-Pérez C et al. Of genes and phenotypes: the immunological and molecular spectrum of combined immune deficiency: defects of the gamma(c)-JAK3 signaling pathway as a model. Immunol Rev 2000; 178: 39–48.

    Article  CAS  Google Scholar 

  8. Arpaia E, Shahar M, Dadi H, Cohen A, Roifman CM . Defective T cell receptor signaling and CD8+ thymic selection in humans lacking Zap-70 kinase. Cell 1994; 76: 947–958.

    Article  CAS  Google Scholar 

  9. Sharfe N, Dadi HK, Shahar M, Roifman CM . Human immune disorder arising from mutation of the á chain of the interleukin-2 receptor. Proc Natl Acad Sci USA 1997; 94: 3168–3171.

    Article  CAS  Google Scholar 

  10. Alarcon B, Regueiro JR, Arnaiz-Villena A, Terhorst C . Familial defect in the surface of expression of the T-cell receptor CD3 complex. N Engl J Med 1988; 319: 1203–1208.

    Article  CAS  Google Scholar 

  11. Sharfe N, Shahar M, Roifman CM . An interleukin-2 receptor γ chain mutation with normal thymus morphology. J Clin Invest 1997; 100: 3036–3043.

    Article  CAS  Google Scholar 

  12. Somech R, Roifman CM . Mutation analysis should be performed to rule out γc deficiency in children with functional severe combined immune deficiency despite apparently normal immunologic tests. J Pediatr 2005; 147: 555–557.

    Article  CAS  Google Scholar 

  13. Roifman CM . Studies of patients’ thymi aid in the discovery and characterization of immunodeficiency in humans. Immunol Rev 2005; 203: 143–155.

    Article  CAS  Google Scholar 

  14. Zhang J, Quintal L, Atkinson A, Williams B, Grunebaum E, Roifman CM . Novel RAG1 mutation in a case of severe combined immunodeficiency. Pediatrics 2005; 116: e445–e449.

    Article  Google Scholar 

  15. Roifman CM, Gu Y, Cohen A . Mutations in the RNA component of RNase MRP cause Omenn Syndrome. J Allergy Clin Immunol 2006; 117: 897–903.

    Article  CAS  Google Scholar 

  16. Hirschhorn R . Overview of biochemical abnormalities and molecular genetics of adenosine deaminase deficiency. Pediatr Res 1993; 33 (1 Suppl): S35–S41.

    Article  CAS  Google Scholar 

  17. Fischer A, Friedrich W, Fasth A, Blanche S, Le Deist F, Girault D et al. Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis and Fanconi's anemia: a European group for immunodeficiency/European Group for Bone Marrow Transplantation report. Blood 1991; 77: 249–256.

    CAS  PubMed  Google Scholar 

  18. Tsuji Y, Imai K, Kajiwara M, Aoki Y, Isoda T, Tomizawa D et al. Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team. Bone Marrow Transplant 2006; 37: 469–477.

    Article  CAS  Google Scholar 

  19. Dalal I, Reid B, Doyle J, Freedman M, Calderwood S, Saunders F et al. Matched unrelated bone marrow transplantation for combined immunodeficiency. Bone Marrow Transplant 2000; 25: 613–621.

    Article  CAS  Google Scholar 

  20. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  Google Scholar 

  21. Guggenheim R, Somech R, Grunebaum E, Atkinson A, Roifman CM . Bone marrow transplantation for cartilage-hair-hypoplasia. Bone Marrow Transplant 2006; 38: 751–756.

    Article  CAS  Google Scholar 

  22. Notarangelo L, Casanova JL, Conley ME, Chapel H, Fischer A, Puck J et al. International union of immunological societies primary immunodeficiency diseases classification committee: primary immunodeficiency diseases. J Allergy Clin Immunol 2006; 117: 883–896.

    Article  Google Scholar 

  23. Filipovich AH, Shapiro RS, Ramsay NK, Kim T, Blazar B, Kersey J et al. Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies. Blood 1992; 80: 270–276.

    CAS  PubMed  Google Scholar 

  24. Grunebaum E, Mazzolari E, Porta F, Dallera D, Atkinson A, Reid B et al. Bone marrow transplantation for severe combined immune deficiency. JAMA 2006; 295: 508–518.

    Article  CAS  Google Scholar 

  25. 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  Google Scholar 

  26. Barker JN, Krepski TP, DeFor TE, Davies SM, Wagner JE, Weisdorf DJ . Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant 2002; 8: 257–260.

    Article  Google Scholar 

  27. Anasetti C, Petersdorf EW, Martin PJ, Woolfrey A, Hansen JA . Trends in transplantation of hematopoieticstem cells from unrelated donors. Curr Opin Hematol 2001; 8: 337–341.

    Article  CAS  Google Scholar 

  28. Stroncek D, Bartsch G, Perkins HA, Randall BL, Hansen JA, McCullough J . The national marrow donor program. Transfusion 1993; 33: 567–577.

    Article  CAS  Google Scholar 

  29. Tiercy JM, Bujan-Lose M, Chapuis B, Gratwohl A, Gmür J, Seger R et al. Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/CwDRB1/B3/B5/DQB1-matched donor? Bone Marrow Transplant 2000; 26: 437–441.

    Article  CAS  Google Scholar 

  30. Candusso M, Faraguna D, Landini P . Artifical nutrition and bone marrow transplantation. Haematologica 2000; 85: 58–61.

    CAS  PubMed  Google Scholar 

  31. Bertrand Y, Landais P, Friedrich W, Gerritsen B, Morgan G, Fasth A et al. Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European group for bone marrow transplantation and the European society for immunodeficiency. J Pediatr 1999; 134: 740–748.

    Article  CAS  Google Scholar 

  32. Martin P, Bleyzac N, Souillet G, Galambrun C, Bertrand Y, Maire PH et al. Clinical and pharmacological risk factors for acute graft-versus-host disease after paediatric bone marrow transplantation from matched-sibling or unrelated donors. Bone Marrow Transplant 2003; 32: 881–887.

    Article  CAS  Google Scholar 

  33. Yang YL, Lu MY, Jou ST, Lin KH, Lin DT . Matched-unrelated-donor bone marrow transplantation for children with leukemia. J Formos Med Assoc 2005; 104: 448–451.

    PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by The Canadian Centre for Primary Immunodeficiency, The Canadian Immunodeficiency Society and The Jeffrey Modell Foundation. CMR is holder of the Donald and Audrey Campbell Chair in Immunology.

Author information

Authors and Affiliations

  1. Division of Immunology and Allergy, The Hospital for Sick Children and The University of Toronto, Toronto, Ontario, Canada

    C M Roifman, R Somech & E Grunebaum

Authors
  1. C M Roifman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Somech
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Grunebaum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C M Roifman.

Additional information

Conflict of interest

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roifman, C., Somech, R. & Grunebaum, E. Matched unrelated bone marrow transplant for T+ combined immunodeficiency. Bone Marrow Transplant 41, 947–952 (2008). https://doi.org/10.1038/bmt.2008.11

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.11

Keywords

This article is cited by

Search

Advanced search

Quick links