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

Long-term adverse effects on dentition in children with poor-risk neuroblastoma treated with high-dose chemotherapy and autologous stem cell transplantation with or without total body irradiation

Abstract

Chemo- and radiotherapy may have injurious effects on developing teeth. In this long-term follow-up study among poor-risk neuroblastoma (NBL) survivors our aims were: (1) to assess both the type and extent of the side-effects of the anticancer treatment on tooth development; and (2) to develop an index for expressing total damage to the permanent dentition. We studied the dental development from panoramic radiographs (PRG) of 18 long-term survivors treated under the age of 6 years with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) for poor-risk NBL. The myeloablative therapy was either HD chemotherapy and fractionated total body irradiation (TBI) of 10–12 Gy (TBI group, n = 10) or HD chemotherapy only (non-TBI group, n = 8). A defect index (DeI) was developed to describe the damage to the permanent dentition. The DeI was also tested in 18 healthy adolescents. All NBL patients had disturbances in dental development including short roots, arrested root development, microdontia and tooth aplasia. After TBI, 9/10 patients had very severe root defects, in contrast to none in the non-TBI group. All children in the TBI group had 2–12 (mean 6.6) missing permanent teeth, while 2/5 in the non-TBI group (3/8 excluded due to young age) had two and four missing permanent teeth, respectively. Microdontia was found at equal frequency in both groups. The mean value of the DeI was 70.0 (range 28–117) in the TBI group, 15.2 (range 4–34) in the non-TBI group (P < 0.001, Mann–Whitney U test) and 1.8 (range 0–15) in healthy adolescents. Disturbances in dental development may compromise occlusal function in poor-risk NBL patients after ASCT, especially when TBI is included in the conditioning regimen. Long-term dental follow-up and rehabilitation is required.

Bone Marrow Transplantation (2002) 29, 121–127. doi:10.1038/sj.bmt.1703330

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 3
Figure 1
Figure 2

Similar content being viewed by others

References

  1. Ogilvy-Stuart AL, Clark DJ, Wallace WHB et al. Endocrine deficit after fractionated total body irradiation Arch Dis Child 1992 67: 1107 1110

    Article  CAS  Google Scholar 

  2. Michel G, Socié F, Gebhard F et al. Late effects of allogenic 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 Société Francaise de Greffe de Moelle J Clin Oncol 1997 15: 2238 2246

    Article  CAS  Google Scholar 

  3. Taskinen M, Saarinen-Pihkala UM, Hovi L et al. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood Lancet 2000 356: 993 997

    Article  CAS  Google Scholar 

  4. Hovi L, Rajantie J, Perkkiö M et al. Growth failure and growth hormone deficiency in children after bone marrow transplantation for leukemia Bone Marrow Transplant 1990 5: 183 186

    CAS  PubMed  Google Scholar 

  5. Hovi L, Saarinen-Pihkala UM, Vettenranta K et al. Growth in children with poor-risk neuroblastoma after regimens with or without total body irradiation in preparation for autologous bone marrow transplantation Bone Marrow Transplant 1999 24: 1131 1136

    Article  CAS  Google Scholar 

  6. Pihkala J, Happonen JM, Virtanen K et al. Cardiopulmonary evaluation of exercise tolerance after chest irradiation and anticancer chemotherapy in children and adolescents Pediatrics 1995 95: 722 726

    CAS  PubMed  Google Scholar 

  7. Pihkala J, Saarinen UM, Lundström U et al. Effects of bone marrow transplantation on myocardial function in children Bone Marrow Transplant 1994 13: 149 155

    CAS  Google Scholar 

  8. Loebstein R, Atanakovic G, Bishai R et al. Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children J Clin Pharmacol 1999 39: 454 461

    CAS  PubMed  Google Scholar 

  9. Ilveskoski I, Saarinen UM, Wiklund T et al. Ototoxicity in children with malignant brain tumors treated with the ‘8 in 1’ chemotherapy protocol Med Pediatr Oncol 1996 27: 26 31

    Article  CAS  Google Scholar 

  10. Nygaard R, Garmicz S, Haldorsen T et al. Second malignant neoplasms in patients treated for childhood leukemia. Apopulation-based cohort study from the Nordic countries Acta Paediatr Scand 1991 80: 1220 1228

    Article  CAS  Google Scholar 

  11. Hovi L, Era P, Rautonen J, Siimes MA . Impaired muscle strength in female adolescents and young adults surviving leukemia in childhood Cancer 1993 72: 276 281

    Article  CAS  Google Scholar 

  12. Arikoski P, Komulainen J, Voutilainen R et al. Reduced bone mineral density in long-term survivors of childhood acute lymphoblastic leukemia Pediatr Hematol Oncol 1998 20: 234 240

    Article  CAS  Google Scholar 

  13. Puukko LR, Hirvonen E, Aalberg V et al. Impaired body image of young female surviving childhood leukemia Psychosomatics 1997 38: 54 62

    Article  CAS  Google Scholar 

  14. Maguire A, Craft A, Evans R et al. The long term effects of treatment on the dental condition of children surviving malignant disease Cancer 1987 60: 2570 2575

    Article  CAS  Google Scholar 

  15. Sonis AL, Tarbell N, Valachovic RW et al. Dentofacial development in long-term survivors of acute lymphoblastic leukemia Cancer 1990 66: 2645 2652

    Article  CAS  Google Scholar 

  16. Goho C . Chemoradiation therapy: effect on dental development Pediatr Dent 1993 15: 6 12

    CAS  PubMed  Google Scholar 

  17. Näsman M, Björk O, Söderhäll S et al. Disturbances in the oral cavity in pediatric long-term survivors after different forms of antineoplastic therapy Pediatr Dent 1994 16: 217 223

    PubMed  Google Scholar 

  18. Näsman M, Forsberg C-M, Dahllöf G . Long-term dental development in children after treatment for malignant disease Eur J Orthod 1997 19: 151 159

    Article  Google Scholar 

  19. Thesleff I, Vaahtokari A, Kettunen P, Åberg T . Epithelial-mesenchymal signaling during tooth development Connect Tissue Res 1995 32: 9 15

    Article  CAS  Google Scholar 

  20. Schour I, Massler M . Studies in tooth development: the growth pattern of human teeth. Parts I and II J Am Dent Assoc 1940 27: 1778 1793 1918 1931

    Article  Google Scholar 

  21. Kreiborg S, Rasmussen P, Thesleff I . Normal dental and occlusal development. In: Koch G, Modeér T, Poulsen S, Rasmussen P (eds) Pedodontics – A Clinical Approach Munksgaard: Copenhagen 1991 pp 42 64

    Google Scholar 

  22. Katzenstein HM, Cohn SL . Advances in the diagnosis and treatment of neuroblastoma Curr Opin Oncol 1998 10: 43 51

    Article  CAS  Google Scholar 

  23. Dini G, Lanino E, Garaventa D et al. Myeloablative therapy and unpurged autologous bone marrow transplantation for poor-prognosis neuroblastoma: report of 34 cases J Clin Oncol 1991 9: 962 969

    Article  CAS  Google Scholar 

  24. Kushner BH, O'Reilly RJ, Mandell LR et al. Myeloablative combination chemotherapy without total body irradiation for neuroblastoma J Clin Oncol 1991 9: 274 279

    Article  CAS  Google Scholar 

  25. Saarinen UM, Wikström S, Mäkipernaa A et al. In vivo purging of bone marrow in children with poor-risk neuroblastoma for marrow collection and autologous bone marrow transplantation J Clin Oncol 1996 14: 2791 2802

    Article  CAS  Google Scholar 

  26. Kaste SC, Hopkins KP, Bowman LC, Santana VM . Dental abnormalities in children treated for neuroblastoma Med Ped Oncol 1998 30: 22 27

    Article  CAS  Google Scholar 

  27. Lind V . Short root anomaly Scand J Dent Res 1972 80: 85 93

    CAS  PubMed  Google Scholar 

  28. Nyström M, Aine L, Peck L et al. Dental maturity in Finns and the problem of missing teeth Acta Odontol Scand 2000 58: 49 56

    Article  Google Scholar 

  29. Jernvall J, Thesleff I . Reiterative signaling and patterning during mammalian tooth morphogenesis Mech Develop 2000 92: 19 29

    Article  CAS  Google Scholar 

  30. Lyaruu DM, van Duin MA, Bervoets TJ et al. Effect of vincristine on the developing hamster tooth germ in vitro Connect Tissue Res 1995 32: 281 289

    Article  CAS  Google Scholar 

  31. Lyaruu DM, van Duin MA, Bervoets TJ et al. Effects of actinomycin D on developing hamster molar tooth germs in vitro Eur J Oral Sci 1997 105: 52 58

    Article  CAS  Google Scholar 

  32. Lyaruu DM, van Duin MA, Bervoets TJ et al. Daunorubicin-induced pathology in the developing hamster molar tooth germ in vitro Cancer Detect Prev 1999 23: 343 350

    Article  CAS  Google Scholar 

  33. Woltgens JH, Lyaruu DM, Bronckers AL et al. Effect of methotrexate on cell proliferation in developing hamster molar tooth germs in vitro Eur J Oral Sci 1998 106 (Suppl. 1): 156 159

    Article  Google Scholar 

  34. Fromm M, Littman P, Raney B et al. Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck: experience at a single institution with a review of the literature Cancer 1986 57: 2070 2076

    Article  CAS  Google Scholar 

  35. Dahllöf G, Barr M, Bolme P et al. Disturbances in dental development after total body irradiation in bone marrow transplant recipients Oral Surg Oral Med Oral Pathol 1988 65: 41 44

    Article  Google Scholar 

  36. Haavikko K . Hypodontia of permanent teeth. An orthopantomographic study Proc Finn Dent Soc 1971 67: 219 225

    CAS  Google Scholar 

  37. Haavikko K . The formation and the alveolar and clinical eruption of the permanent teeth. An orthopantomographic study Proc Finn Dent Soc 1970 66: 103 170

    CAS  Google Scholar 

  38. Chung CS, Niswander JD, Runck DW et al. Genetic and epidemiological studies of oral characteristics of Hawaii schoolchildren: dental anomalies Am J Phys Anthropol 1972 20: 427 433

    Article  Google Scholar 

  39. Ooshima T, Ishida R, Mishima K et al. The prevalence of developmental anomalies of teeth and their association with tooth size in the primary and permanent dentitions of 1650 Japanese children Int J Paediatr Dent 1996 6: 87 94

    Article  CAS  Google Scholar 

  40. Logan W, Kronfeld R . Development of the human jaws and surrounding structures from birth to the age of fifteen years J Am Dent Assoc 1933 20: 379 427

    Google Scholar 

  41. Apajalahti S, Hölttä P, Turtola L et al. Prevalence of short root anomaly in healthy young adults Acta Odont Scand (in press)

Download references

Acknowledgements

This study was supported by a grant from the Finnish Dental Association Apollonia.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hölttä, P., Alaluusua, S., Saarinen-Pihkala, U. et al. Long-term adverse effects on dentition in children with poor-risk neuroblastoma treated with high-dose chemotherapy and autologous stem cell transplantation with or without total body irradiation. Bone Marrow Transplant 29, 121–127 (2002). https://doi.org/10.1038/sj.bmt.1703330

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703330

Keywords

This article is cited by

Search

Quick links