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:

Post-Transplant Complications

Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood

Bone Marrow Transplantation volume 33, pages 1049–1056 (2004)Cite this article

Summary:

It is generally assumed that busulphan/cyclophoshamide (Bu/Cy)-based conditioning regimens for haematopoietic stem cell transplantation (SCT) do not affect growth. We evaluated growth and endocrine function after Bu/Cy-based conditioning in 64 children without a history of irradiation. Mean height standard deviation scores remained stable, but unexplained disturbances of growth after SCT were found in 17/48 (35%) of the children without growth-limiting disorders (10/23 in patients treated for haematological malignancies). In 10 patients, growth hormone (GH) secretion status was evaluated, and insufficient GH secretion was diagnosed in four patients. Thyroid function was evaluable in 52 patients. Two developed antibody-mediated thyroid disorders and 10 (19%) compensated primary hypothyroidism. Gonadal function was evaluable in 21 patients and was normal in all seven patients treated with low-dose Bu (8 mg/kg), whereas seven of the 14 children receiving high-dose Bu (16–20 mg/kg) developed gonadal failure; the majority of these patients had not been exposed to gonadotoxic therapy prior to Bu/Cy. Of the 49 evaluable patients, 16 developed subclinical hyperparathyroidism. We conclude that, besides gonadal and thyroid dysfunction, impaired growth and hyperparathyroidism often occur after Bu/Cy conditioning for SCT and that growth impairment may be the result of insufficient GH secretion.

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

Similar content being viewed by others

References

  1. Giorgiani G, Bozzola M, Locatelli F et al. Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone. Blood 1995; 86: 825–831.

    CAS  Google Scholar 

  2. Shankar SM, Bunin NJ, Moshang T . Growth in children undergoing bone marrow transplantation after busulfan and cyclophosphamide conditioning. J Pediatr Hematol Oncol 1996; 18: 366.

    Google Scholar 

  3. Michel G, Socié 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 

  4. Cohen A, Rovelli A, Bakker B et al. Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the Working Party for Late Effects – EBMT. Blood 1999; 93: 4109–4115.

    CAS  Google Scholar 

  5. 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 

  6. Fredriks AM, van Buuren S, Burgmeijer RJ et al. Continuing positive secular growth change in The Netherlands 1955–1997. Pediatr Res 2000; 47: 316–323.

    Article  CAS  Google Scholar 

  7. Albertsson-Wikland K, Rosberg S . Physiological GH secretion: changes with age, stature and puberty. In: Savage MO, Bourguignon JP, Grossman AB (eds.). Frontiers in Paediatric Neuroendocrinology. Blackwell Science Ltd.: Boston, MA, 1994; pp 131–137.

    Google Scholar 

  8. Jansson C, Boguszewski C, Rosberg S et al. Growth hormone (GH) assays: influence of standard preparations, GH isoforms, assay characteristics, and GH-binding protein. Clin Chem 1997; 43: 950–956.

    CAS  PubMed  Google Scholar 

  9. Rikken B, van Doorn J, Ringeling A et al. Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein-3 in the evaluation of childhood growth hormone deficiency. Horm Res 1998; 50: 166–176.

    CAS  PubMed  Google Scholar 

  10. Bercu BB, Diamond Jr FB . Growth hormone neurosecretory dysfunction. Clin Endocrinol Metab 1986; 15: 537–590.

    Article  CAS  Google Scholar 

  11. Albertsson-Wikland K, Lannering B, Marky I et al. A longitudinal study on growth and spontaneous growth hormone (GH) secretion in children with irradiated brain tumors. Acta Paediatr Scand 1987; 76: 966–973.

    Article  CAS  Google Scholar 

  12. Darzy KH, Shalet SM . Radiation-induced growth hormone deficiency. Horm Res 2003; 59: 1–11.

    CAS  PubMed  Google Scholar 

  13. Brennan BM, Shalet SM . Endocrine late effects after bone marrow transplant. Br J Haematol 2002; 118: 58–66.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. 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 

  16. 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 

  17. Tauchmanova L, Selleri C, Rosa GD 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 

  18. Sarafoglou K, Boulad F, Gillio A, Sklar C . Gonadal function after bone marrow transplantation for acute leukemia during childhood. J Pediatr 1997; 130: 210–216.

    Article  CAS  Google Scholar 

  19. Bakker B, Massa GG, Oostdijk W et al. Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies. Eur J Pediatr 2000; 159: 31–37.

    Article  CAS  Google Scholar 

  20. Couto-Silva AC, Trivin C, Thibaud E et al. Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplant 2001; 28: 67–75.

    Article  CAS  Google Scholar 

  21. DeSanctis V, Galimberti M, Lucarelli G et al. Gonadal function after allogenic bone marrow transplantation for thalassaemia. Arch Dis Child 1991; 66: 517–520.

    Article  CAS  Google Scholar 

  22. Sanders JE . Growth and development after hematopoietic cell transplantation. In: Thomas ED, Blume KG, Forman SJ (eds.). Hematopoietic Cell Transplantation. Blackwell Science Inc.: Malden, MA, 1999; pp 764–775.

    Google Scholar 

  23. Byrne J, Fears TR, Gail MH et al. Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol 1992; 166: 788–793.

    Article  CAS  Google Scholar 

  24. Schneider AB, Gierlowski TC, Shore-Freedman E et al. Dose–response relationships for radiation-induced hyperparathyroidism. J Clin Endocrinol Metab 1995; 80: 254–257.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was sponsored by a grant from NWO, The Netherlands' Organization for Scientific Research.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

    B Bakker, W Oostdijk, D Bresters, M J E Walenkamp, J M Vossen & J M Wit

Authors
  1. B Bakker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W Oostdijk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Bresters
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M J E Walenkamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J M Vossen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J M Wit
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B Bakker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bakker, B., Oostdijk, W., Bresters, D. et al. Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood. Bone Marrow Transplant 33, 1049–1056 (2004). https://doi.org/10.1038/sj.bmt.1704481

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704481

Keywords

This article is cited by

Search

Advanced search

Quick links