Immunologic Research

, Volume 38, Issue 1–3, pp 165–173

Long-term follow-up in patients with severe combined immunodeficiency treated by bone marrow transplantation

  • Wilhelm Friedrich
  • Manfred Hönig
  • Susanna M. Müller


Immune reconstitution was studied in 31 long-term surviving patients after bone marrow transplantation for severe combined immunodeficiency. Donors in 7 cases were HLA-identical and in 25 cases HLA-haploidentical family members, and in 13 of these latter cases cytoreductive conditioning had been used prior to transplantation. At a mean follow-up of 15 years after transplantation (range 10 to 22 years), T cell numbers and functions had remained stable and within normal limits in the majority of patients. Marked variability however was observed with regard to reconstitution of B cell immunity. Furthermore numbers of circulating naïve CD4+ T cells were variable and markedly diminished in a substantial proportion of patients at recent evaluations. Normal B cell immunity and persistently normal naïve T cell numbers were strongly correlated with the continued detection of donor type CD34+ precursor cells in the patients marrow, which were absent in non conditioned patients. These findings indicate that stable donor precursor cell engraftment in the marrow may be of relevance for complete and stable long-term immune reconstitution in transplanted SCID patients.


Severe combined immunodeficiency SCID Bone marrow transplantation Immune reconstitution 


  1. 1.
    Gatti RA, Meeuwissen HJ, et al. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 1968;2:1366–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Reisner Y, Kapoor N, Kirkpatrick D, 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;61:341–8.PubMedGoogle Scholar
  3. 3.
    Antoine C, Friedrich W, Cant A, et al. Long term survival and hematopoietic stem-cell transplantation for immuno-deficiencies. A survey of the European experience. Lancet 2003;361:553–60, (1968–1999).PubMedCrossRefGoogle Scholar
  4. 4.
    Grunebaum E, Mazzolare E, Porta F, et al. Bone marrow transplantation for severe combined immune deficiency. YAMA 2006;295(5):508–18.Google Scholar
  5. 5.
    Müller SM, Kohn T, Schulz A, et al. Similar pattern of thymic-dependent T-cell reconstitution in infants with severe combined immunodeficiency after human leukocyte antigen (HLA)-identical and HLA-nonidentical stem cell transplantation. Blood 2000;96(13):4344–9, Dec 15.PubMedGoogle Scholar
  6. 6.
    Fischer A, Landais P, Friedrich W, et al. European experience of bone marrow transplantation for severe combined immunodeficiency. Lancet 1990;2:850–4.CrossRefGoogle Scholar
  7. 7.
    Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, Myers LA, Ward FE, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 1999;340:508–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Förster I, Rajewsky K. The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow. Proc Natl Acad Sci USA 1990;87:4781–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Patel DD, Gooding ME, Parrott RE, Curtis KM, Haynes BF, Buckley RH, et al. Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 2000;342:1325–32.PubMedCrossRefGoogle Scholar
  10. 10.
    Frey JR, Ernst B, Surh CD, Sprent H. Thymus-grafted SCID mice show transient thymopoiesis and limited depletion of V beta 11+ T cells. J Exp Med 1992;175:1067–71.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Wilhelm Friedrich
    • 1
  • Manfred Hönig
    • 1
  • Susanna M. Müller
    • 1
  1. 1.Department of PediatricsUniversity of UlmUlmGermany

Personalised recommendations