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Post-Transplant Complications

Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning

Bone Marrow Transplantation volume 33, pages 949–953 (2004)Cite this article

Summary:

Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon.

Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.

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References

  1. Buckley RH . Treatment options for genetically determined immunodeficiency. Lancet 2003; 361: 541–542.

    Article  Google Scholar 

  2. Antoine C, Muller S, Cant A et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. Lancet 2003; 361: 553–560.

    Article  Google Scholar 

  3. Gennery AR, Dickinson AM, Brigham K et al. CAMPATH-1M T cell depleted bone marrow transplantation for severe combined immunodeficiency: long term follow up of 19 children treated in the period 1987–1998 in a single centre. Cytotherapy 2001; 3: 221–232.

    Article  CAS  Google Scholar 

  4. Slatter MA, Bhattacharya A, Flood TJ et al. Polysaccharide antibody responses are impaired post bone marrow transplantation for severe combined immunodeficiency, but not other primary immunodeficiencies. Bone Marrow Transplant 2003; 32: 225–229.

    Article  CAS  Google Scholar 

  5. Katsanis E, Shapiro RS, Robison LL et al. Thyroid dysfunction following bone marrow transplantation: long-term follow-up of 80 pediatric patients. Bone Marrow Transplant 1990; 5: 335–340.

    CAS  Google Scholar 

  6. Wedderburn LR, Jeffery R, White H et al. Autologous stem cell transplantation for paediatric-onset polyarteritis nodosa: changes in autoimmune phenotype in the context of reduced diversity of the T and B cell repertoires, and evidence for reversion from the CD45RO+ to RA+ phenotype. Rheumatology 2001; 40: 1299–1307.

    Article  CAS  Google Scholar 

  7. Al-Fiar FZ, Colwill R, Lipton JH et al. Abnormal thyroid stimulating hormone (TSH) levels in adults following allogeneic bone marrow transplants. Bone Marrow Transplant 1997; 19: 1019–1022.

    Article  CAS  Google Scholar 

  8. Toubert M-E, Socie G, Gluckman E et al. Short and long-term follow-up of thyroid dysfunction after allogeneic bone marrow transplantation without the use of preoperative total body irradiation. Br J Haematol 1997; 98: 453–457.

    Article  CAS  Google Scholar 

  9. Kami M, Tanaka Y, Chiba S et al. Thyroid function after bone marrow transplantation: possible association between immune-mediated thyrotoxicosis and hypothyroidism. Transplantation 2001; 71: 406–411.

    Article  CAS  Google Scholar 

  10. Sherer Y, Shoenfeld Y . Autoimmune diseases and autoimmunity post bone marrow transplantation. Bone Marrow Transplant 1998; 22: 873–881.

    Article  CAS  Google Scholar 

  11. Michel G, Socie G, Gebhard F et al. Late effects of allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: the impact of conditioning regimen without total-body irradiation — a report from the Societe Francaise de greffe de moelle. J Clin Oncol 1997; 15: 2238–2246.

    Article  CAS  Google Scholar 

  12. Afify Z, Shaw PJ, Clavano-Harding A, Cowell CT . Growth and endocrine function in children with acute myeloid leukaemia after bone marrow transplantation using busulfan/cyclophosphamide. Bone Marrow Transplant 2000; 25: 1087–1092.

    Article  CAS  Google Scholar 

  13. Chapel H, Geha R, Rosen F, (IUIS PID classification committee). Primary immunodeficiency disease: an update. Clin Exp Immunol 2003; 132: 9–15.

    Article  CAS  Google Scholar 

  14. Przepiorka D, Weisdorf D, Martin P et al. Consensus conference on acute GvHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  15. Gluckberg H, Storb R, Fefer A et al. Clinical manifestations of GvHD in human recipients of marrow from HLA matched sibling donors. Transplant 1974; 18: 295–304.

    Article  Google Scholar 

  16. Tauchmanova L, Selleri C, De Rosa G et al. High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases. Cancer 2002; 95: 1076–1084.

    Article  Google Scholar 

  17. Tunbridge WMG, Evered DC, Hall R et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol 1977; 7: 481–493.

    Article  CAS  Google Scholar 

  18. De Groot LJ . Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metabol 1999; 84: 151–164.

    Article  CAS  Google Scholar 

  19. Karthaus M, Gabrysiak T, Brabant G et al. Immune thyroiditis after transplantation of allogeneic CD34+ selected peripheral blood cells. Bone Marrow Transplant 1997; 20: 697–699.

    Article  CAS  Google Scholar 

  20. Devendra D, Eisenbarth GS . Immunologic endocrine disorders. J Allergy Clin Immunol 2003; 111: s624–s636.

    Article  CAS  Google Scholar 

  21. Arkwright PD, Abinun M, Cant AJ . Autoimmunity in human primary immunodeficiency diseases. Blood 2002; 99: 2694–2702.

    Article  CAS  Google Scholar 

  22. Dupuis-Girrod S, Medioni J, Haddad E et al. Autoimmunity in Wiskott–Aldrich syndrome: risk factors, clinical features, and outcome in a single-centre cohort of 55 patients. Pediatrics 2003; 111: e622–e627.

    Article  Google Scholar 

  23. Schurman SH, Candotti F . Autoimmunity in Wiskott–Aldrich syndrome. Curr Opin Rheumatol 2003; 15: 446–453.

    Article  CAS  Google Scholar 

  24. Olivares JL, Ramos FJ, Olive T et al. Autoimmune thyroiditis after bone marrow transplantation in a boy with Wiskott–Aldrich syndrome. J Pediatr Hematol/Oncol 2002; 24: 772–776.

    Article  Google Scholar 

  25. Gambineri E, Torgerson TR, Ochs HD . Immune dysregulation, polyendocrinopathy, enteropathy, and x-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003; 15: 430–435.

    Article  CAS  Google Scholar 

  26. Kaino Y, Otoh Y, Tokuda K et al. Acquired hypothyroidism in a very young infant with Omenn's syndrome. J Pediatr 2000; 136: 111–113.

    Article  CAS  Google Scholar 

  27. Trendelenburg M, Gregor M, Passweg J et al. ‘Altered immunity syndrome’, a distinct entity in long-term bone marrow transplantation survivors? Bone Marrow Transplant 2001; 28: 1175–1177.

    Article  CAS  Google Scholar 

  28. Coles AJ, Wing M, Smith S et al. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 1995; 354: 1691–1695.

    Article  Google Scholar 

  29. Todd A, Todd J . Graves' disease following successful treatment of severe aplastic anaemia with antilymphocyte globulin. Clin Lab Haem 1999; 21: 69–70.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatric Immunology Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK

    M A Slatter, A R Gennery, A Bhattacharya, B N A Crooks, T J Flood, A J Cant & M Abinun

  2. Department of Endocrinology, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK

    T D Cheetham

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  1. M A Slatter
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  2. A R Gennery
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  3. T D Cheetham
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  4. A Bhattacharya
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  5. B N A Crooks
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  6. T J Flood
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  7. A J Cant
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  8. M Abinun
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Correspondence to M Abinun.

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Slatter, M., Gennery, A., Cheetham, T. et al. Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning. Bone Marrow Transplant 33, 949–953 (2004). https://doi.org/10.1038/sj.bmt.1704456

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  • DOI: https://doi.org/10.1038/sj.bmt.1704456

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