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Post-Transplant Complications

Factors affecting gonadal function after bone marrow transplantation during childhood

Abstract

Conditioning for bone marrow transplantation (BMT) may alter viability of germ cells and production of gonadal hormones. We analyzed the risk factors for gonadal failure after 12 Gy total body irradiation (TBI) given as six fractions (n = 31, group 1), 10 Gy (one dose) TBI (n = 20, group 2), 6 Gy (one dose) total lymphoid irradiation (TLI, n = 17, group 3) and chemotherapy alone (n = 7, group 4), given at 7.7 ± 0.4 (0.6–13.6) years. Among the 34 girls, seven (20.6%) had normal ovarian function with regular spontaneous menstruation and normal plasma follicle-stimulating (FSH) and luteinizing (LH) hormones, five (14.7%) had partial ovarian failure with regular menstruation but increased FSH and/or LH, and 22 (64.7%) had complete ovarian failure. The 24 girls with chronological and bone ages >13 years included similar percentages, with increased FSH or LH in all four groups. There was a positive correlation between age at BMT and FSH (r = 0.54, P < 0.01), but not with LH, and between FSH and LH (r = 0.8, P = 0.0003). Plasma FSH concentrations had returned to normal spontaneously in six cases, and those of LH in two cases. Among the 41 boys, 16 (39%) had normal testicular function and 25 (61%) had tubular failure and increased FSH. Of these, 10 also had Leydig cell failure (three complete and seven partial). The 18 boys with chronological and bone ages >15 years included similar percentages with increased FSH or LH in groups 1 to 3, and testicular volume was significantly lower in group 2 than in group 3 (P = 0.008). There was no correlation between age at BMT and FSH, LH or testosterone, but there was a negative correlation between FSH and inhibin B (rho = −0.87, P < 0.003). We conclude that girls are more likely to suffer ovarian failure the older they are at BMT, and that early ovarian recovery is possible. The negative correlation between FSH and inhibin B in boys suggests that this parameter is an additional indicator of tubular function. Bone Marrow Transplantation (2001) 28, 67–75.

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References

  1. Sanders JE, Buckner CD, Amos D et al. Ovarian function following marrow transplantation for aplastic anemia or leukemia J Clin Oncol 1988 6: 813–818

    Article  CAS  Google Scholar 

  2. 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 

  3. Clement-De Boers A, Oostdijk W, Van Weel-Sipman MH et al. Final height and hormonal function after bone marrow transplantation in children J Pediatr 1996 129: 544–550

    Article  CAS  Google Scholar 

  4. Sanders JE, Hawley J, Levy W et al. Pregnancies following high dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation Blood 1996 87: 3045–3052

    CAS  Google Scholar 

  5. Thibaud E, Rodriguez-Macias K, Trivin C et al. Ovarian function after bone marrow transplantation during childhood Bone Marrow Transplant 1998 21: 287–290

    Article  CAS  Google Scholar 

  6. Couto-Silva AC, Trivin C, Esperou H et al. Changes in weight and plasma leptin after bone marrow transplantation Bone Marrow Transplant 2000 26: 1205–1210

    Article  CAS  Google Scholar 

  7. Marshall WA, Tanner JM . Variations in the pattern of pubertal changes in girls Arch Dis Child 1969 44: 291–303

    Article  CAS  Google Scholar 

  8. Marshall WA, Tanner JM . Variations in the pattern of pubertal changes in boys Arch Dis Child 1970 45: 13–23

    Article  CAS  Google Scholar 

  9. Burr IM, Sizonenko PC, Kaplan SL, Grumbach MM . Hormonal changes during puberty. I. Correlation of serum luteinizing hormone and follicle-stimulating hormone with stages of puberty, testicular size, and bone age in normal boys Pediatr Res 1970 4: 25–35

    Article  CAS  Google Scholar 

  10. Greulich WW, Pyle SI . Radiographic Atlas of Skeletal Development of the Hand and the Wrist 2nd edn Stanford University Press: Stanford, CA 1959

    Book  Google Scholar 

  11. Groome NP, Illingworth PJ, O'Brien M et al. Measurement of dimeric inhibin B throughout the human menstrual cycle J Clin Endocr Metab 1996 81: 1401–1405

    CAS  PubMed  Google Scholar 

  12. 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 

  13. Mertens AC, Ramsay NKC, Kouris S, Neglia JP . Patterns of gonadal dysfunction following bone marrow transplantation Bone Marrow Transplant 1998 22: 345–350

    Article  CAS  Google Scholar 

  14. Matsumoto M, Shinohara O, Ishiguro H et al. Ovarian function after bone marrow transplantation performed before menarche Arch Dis Child 1999 80: 452–454

    Article  CAS  Google Scholar 

  15. Byrne J, Mulvihill JJ, Connelly RR et al. Reproductive problems and birth defects in survivors of Wilm's tumor and their relatives Med Pediatr Oncol 1988 16: 233–240

    Article  CAS  Google Scholar 

  16. 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 

  17. Brauner R, Caltabiano P, Rappaport R et al. Leydig cell insufficiency after testicular irradiation for acute lymphoblastic leukemia Horm Res 1988 30: 111–114

    Article  CAS  Google Scholar 

  18. Shalet SM, Tsatsoulis A, Whitehead E, Read G . Vulnerability of the human Leydig cell to radiation damage is dependent upon age J Endocrinol 1989 120: 161–165

    Article  CAS  Google Scholar 

  19. Kolb BA, Stanezyk FZ, Sokol RZ . Serum inhibin B levels in males with gonadal dysfunction Fertil Steril 2000 74: 234–238

    Article  CAS  Google Scholar 

  20. Wallace EM, Groome NP, Riley SC et al. Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and testosterone secretion: a prospective longitudinal study J Clin Endocr Metab 1997 82: 3111–3115

    Article  CAS  Google Scholar 

  21. Petersen PM, Andersson AM, Rorth M et al. Undetectable Inhibin B serum levels in men after testicular irradiation J Clin Endocr Metab 1999 84: 213–215

    CAS  PubMed  Google Scholar 

  22. Brauner R, Adan L, Souberbielle JC et al. Contribution of growth hormone deficiency to the growth failure that follows bone marrow transplantation J Pediatr 1997 130: 785–792

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Dr AC Couto-Silva was partly supported by Groupement Français de Gynécologie de l'Enfance et de l'Adolescence.

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Couto-Silva, A., Trivin, C., Thibaud, E. et al. Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplant 28, 67–75 (2001). https://doi.org/10.1038/sj.bmt.1703089

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