Skip to main content

Advertisement

SpringerLink
Log in

Single-center analysis of long-term outcome after hematopoietic cell transplantation in children with congenital severe T cell immunodeficiency

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

We review clinical outcome and immune reconstitution in a consecutive series of 74 infants with severe T cell immunodeficiency who received hematopoietic cell transplantation (HCT) from January 1991 to May 2003. Fifty-three patients (71.6%) are alive. Results were significantly better for recipients of HCT from HLA-matched related donors (100% survival) and unrelated donors (86.4%) than from mismatched related donors (51.6%). A detailed analysis of immune reconstitution and clinical status was performed in 49 surviving patients, most of which have attained robust T and B cell reconstitution and are in very good clinical conditions. No cases of late deaths or of chronic graft-versus-host disease (GvHD) have been observed. However, infections and autoimmunity at >1 year after HCT have been observed in a significant number of patients. Persistence of a low number of circulating naive T cells and long-term requirement for intravenous immunoglobulin were associated with a higher incidence of clinical events.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Fischer A, Notarangelo LD. Combined immunodeficiencies. In: Stiehm ER, Ochs HD, Winkelstein JA, editors. Immunologic disorders in infants and children. Philadelphia, PA: Elsevier; 2004. p. 447–79.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Antoine C, Müller 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  PubMed  Google Scholar 

  4. 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;340:508–16.

    Article  PubMed  CAS  Google Scholar 

  5. 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;99:872–8.

    Article  PubMed  CAS  Google Scholar 

  6. Grunebaum E, Mazzolari E, Porta F, Dallera D, Atkinson A, Reid B, et al. Bone marrow transplantation for severe combined immune deficiency. JAMA. 2006;295:508–18.

    Article  PubMed  CAS  Google Scholar 

  7. Roifman CM, Grunebaum E, Dalal I, Notarangelo L. Matched unrelated bone marrow transplant for severe combined immunodeficiency. Immunol Res. 2007;38:191–200.

    Article  PubMed  Google Scholar 

  8. 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;342:1325–32.

    Article  PubMed  CAS  Google Scholar 

  9. Sarzotti M, Patel DD, Li X, Ozaki DA, Cao S, Langdon S, et al. T cell repertoire development in humans with SCID after nonablative allogeneic marrow transplantation. J Immunol. 2003;170:2711–8.

    PubMed  CAS  Google Scholar 

  10. Borghans JA, Bredius RG, Hazenberg MD, Roelofs H, Jol-van der Zijde EC, Heidt J, et al. Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency. Blood. 2006;108:763–9.

    Article  PubMed  CAS  Google Scholar 

  11. Cavazzana-Calvo M, Carlier F, Le Deist F, Morillon E, Taupin P, Gautier D, et al. Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype. Blood. 2007;109:4575–81.

    Article  PubMed  CAS  Google Scholar 

  12. Mazzolari E, Forino C, Guerci S, Imberbi L, Lanfranchi A, Porta F, et al. Long-term immune reconstitution and clinical outcome after stem-cell transplantation for severe T-cell immunodeficiency. J Allergy Clin Immunol. 2007;120:892–9.

    Article  PubMed  CAS  Google Scholar 

  13. Friedrich W, Hönig M, Müller SM. Long-term follow-up in patients with severe combined immunodeficiency treated by bone marrow transplantation. Immunol Res. 2007;38:165–73.

    Article  PubMed  Google Scholar 

  14. Zhang L, Lewin SR, Markowitz M, Lin H-H, Skulsky E, Karanicolas R, et al. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J Exp Med. 1999;190:725–32.

    Article  PubMed  CAS  Google Scholar 

  15. Roifman CM, Somech R, Grunebaum E. Matched unrelated bone marrow transplant for T+ combined immunodeficiency. Bone Marrow Transplant. 2008;41:947–952.

    Article  PubMed  CAS  Google Scholar 

  16. 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 restrospective study of 116 patients. Blood. 1998;91:3646–53.

    PubMed  CAS  Google Scholar 

  17. Roberts JL, Lengi A, Brown SM, Chen M, Zhou YJ, O’Shea JJ, et al. Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcome of stem cell transplantation. Blood. 2004;103:2009–18.

    Article  PubMed  CAS  Google Scholar 

  18. Slatter MA, Brigham K, Dickinson AM, Harvey HL, Barge D, Jackson A, et al. Long-term immune reconstitution after anti-CD52-treated or anti-CD34-treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency. J Allergy Clin Immunol. 2008;121:361–7.

    Article  PubMed  CAS  Google Scholar 

  19. Oakes SA, Candotti F, Johnston JA, Chen YQ, Ryan JJ, Taylor N, et al. Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes: JAK3-dependent and independent pathways. Immunity. 1996;5:605–15.

    Article  PubMed  CAS  Google Scholar 

  20. Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Morse HC 3rd, et al. A critical role for IL-21 in regulating immunoglobulin production. Science. 2002;298:1630–4.

    Article  PubMed  CAS  Google Scholar 

  21. Bryant VL, Ma CS, Avery DT, Li Y, Good KL, Corcoran LM, et al. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J Immunol. 2007;179:8180–90.

    PubMed  CAS  Google Scholar 

  22. Laffort C, LeDeist F, Favre M, Caillat-Zucman S, Radford-Weiss I, Debrè M, et al. Severe cutaneous papillomavirus disease after haematopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common γc cytokine receptor subunit or JAK3 deficiency. Lancet. 2004;363:2051–4.

    Article  PubMed  CAS  Google Scholar 

  23. Burton C, Kaczmarski R, Jan-Mohamed R. Interstitial pneumonitis related to rituximab therapy. N Engl J Med. 2003;348:2690–1.

    Article  PubMed  Google Scholar 

  24. Wagner SA, Mehta AC, Laber DA. Rituximab-induced interstitial lung disease. Am J Hematol. 2007;82:916–9.

    Article  PubMed  CAS  Google Scholar 

  25. Slatter MA, Gennery AR, Cheetham TD, Bhattacharya A, Crooks BNA, Flood TJ, et al. Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning. Bone Marrow Transplant. 2004;33:949–53.

    Article  PubMed  CAS  Google Scholar 

  26. Puck JM, SCID Newborn Screening Working Group. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. 2007;120:760–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Divisione di Emato-Oncologia Pediatrica, Ospedale dei Bambini, Spedali Civili, Brescia, Italy

    Evelina Mazzolari, Donatella de Martiis, Concetta Forino, Arnalda Lanfranchi, Roberto Marzollo & Fulvio Porta

  2. Dipartimento Materno-infantile e Tecnologie Biomediche, Università di Brescia, Brescia , Italy

    Evelina Mazzolari & Luigi D. Notarangelo

  3. “Angelo Nocivelli” Institute for Molecular Medicine, University of Brescia, Brescia , Italy

    Silvia Giliani

  4. Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy

    Paolo Airò

  5. Laboratorio di Biotecnologie, Diagnostic Department, Spedali Civili, Brescia, Italy

    Luisa Imberti

  6. Division of Immunology, Children’s Hospital, Harvard Medical School, Karp Building, 9th floor, Room 9210, 1 Blackfan Circle, Boston, MA, 02115, USA

    Luigi D. Notarangelo

Authors
  1. Evelina Mazzolari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donatella de Martiis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Concetta Forino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arnalda Lanfranchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silvia Giliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roberto Marzollo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paolo Airò
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Luisa Imberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fulvio Porta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luigi D. Notarangelo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luigi D. Notarangelo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mazzolari, E., de Martiis, D., Forino, C. et al. Single-center analysis of long-term outcome after hematopoietic cell transplantation in children with congenital severe T cell immunodeficiency. Immunol Res 44, 4–17 (2009). https://doi.org/10.1007/s12026-008-8022-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-008-8022-4

Keywords

Search

Navigation