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Fertility

Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg)

Abstract

There are few published data on the recovery of fertility after ‘little’ bu-cy (busulfan 16 mg/kg, cyclophosphamide 120 mg/kg) conditioning for bmt. to address this, we identified 19 females aged less than 40 years at transplant and 47 males from a single centre who were alive a minimum of 2 years after bmt with little bu-cy as conditioning and who were evaluable for testing. fsh, lh, testosterone and inhibin b levels were measured in males. twenty-six also had semen analysis, a median of 5 years post transplant; 21 had detectable sperm, with 11 having counts >20 × 106/ml. There was an association between prolonged chronic graft-versus-host disease and low sperm counts. FSH and inhibin B levels correlated with sperm counts but not to the extent that they could reliably predict counts in individual patients. An additional six of seven males attempting to father children did so, a median of 3.2 years post transplant. Low testosterone levels were noted in 12% of males, most of whom had symptoms consistent with androgen deficiency. FSH, LH and oestradiol levels in the absence of hormone replacement therapy were measured in females; all remained amenorrheic with endocrine evidence of ovarian failure. These results have implications for fertility counselling and hormone replacement therapy both pre- and post BMT. Bone Marrow Transplantation (2000) 26, 1089–1095.

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References

  1. 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  PubMed  Google Scholar 

  2. Copelan EA, Deeg J . Conditioning for allogeneic marrow transplantation in patients with lymphohematopoietic malignancies without the use of total body irradiation Blood 1992 80: 1648–1658

    CAS  PubMed  Google Scholar 

  3. Clark ST, Radford JA, Crowther D et al. Gonadal function following chemotherapy for Hodgkin's disease: a comparative study of MVPP and a seven-drug hybrid regimen J Clin Oncol 1995 13: 134–139

    Article  CAS  Google Scholar 

  4. Grigg AP, Goss G, Szer J . Phase I dose-escalation study of 5-day continuous infusion VP16 plus busulphan-cyclophosphamide as a conditioning regimen prior to autologous transplantation Blood 1994 84: (Suppl. 1) 826

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. Landrieu P, Husson B, Pariente D, Lacroix C . MRI-neuropathological correlations in type 1 lissencephaly Neuroradiology 1998 40: 173–176

    Article  CAS  Google Scholar 

  7. Wallace EM . Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin and testosterone secretion: a prospective longitudinal study J Clin Endocrinol Metab 1997 82: 3111–3115

    Article  CAS  Google Scholar 

  8. Bohring C, Krause W . Serum levels on inhibin B in men with different causes of spermatogenic failure Andrologia 1999 31: 137–141

    Article  CAS  Google Scholar 

  9. Von Eckardstein S, Simoni M, Bergmann M et al. Serum inhibin B in combination with serum follicle-stimulating hormone (FSH) is a more sensitive marker than serum FSH alone for impaired spermatogenesis in men, but cannot predict the presence of sperm in testicular tissue samples J Clin Endocrinol Metab 1999 84: 2496–2501

    CAS  PubMed  Google Scholar 

  10. Behre HM, Yeung CH, Nieschlag E . Diagnosis of male infertility and hypogonadism. In: Nieschlag E, Behre HM (eds). Andrology: Male Reproductive Health and Dysfunction Springer: Heidelberg, 1997 6: 87–114

    Google Scholar 

  11. Wingard JR, Miller DF, Santos GW . Testicular function after busulfan (BU) plus cyclophosphamide (CY) J Cell Biochem 1992 16A: 215 (Abstr. D618)

    Google Scholar 

  12. Chatterjee R, Goldstone AH . Gonadal damage and effects on fertility in adult patients with haematological malignancy undergoing stem cell transplantation Bone Marrow Transplant 1996 17: 5–11

    CAS  PubMed  Google Scholar 

  13. MacAdams MR, White RH, Chipps BE . Reduction of serum testosterone levels during chronic glucocorticoid therapy Ann Intern Med 1986 104: 648–651

    Article  CAS  Google Scholar 

  14. Valimaki MJ, Kinnunen K, Volin L et al. A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin Bone Marrow Transplant 1999 23: 355–361

    Article  CAS  Google Scholar 

  15. Chopra R, McMillan AK, Linch DC et al. The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight-year study of 155 patients Blood 1993 81: 1137–1145

    CAS  PubMed  Google Scholar 

  16. Keilholz U, Max R, Scheibenbogen C et al. Endocrine function and bone metabolism 5 years after autologous bone marrow/blood-derived progenitor cell transplantation Cancer 1997 79: 1617–1622

    Article  CAS  Google Scholar 

  17. Singhal S, Powles R, Treleaven J et al. Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women Bone Marrow Transplant 1996 18: 1049–1055

    CAS  PubMed  Google Scholar 

  18. Atkinson HG, Apperley JF, Dawson K et al. Successful pregnancy after allogeneic bone marrow transplantation for chronic myeloid leukemia Lancet 1994 344: 199

    Article  CAS  Google Scholar 

  19. Castelo-Branco C, Rovira M, Pons F et al. The effect of hormone replacement therapy on bone mass in patients with ovarian failure due to bone marrow transplantation Maturitas 1996 23: 307–312

    Article  CAS  Google Scholar 

  20. Davis S . Androgen replacement in women: a commentary J Clin Endocrinol Metab 1999 84: 1886–1891

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Jack Metz for his helpful comments, Alison Poustie and Peter Shuttleworth for assistance with data collection, Deborah Porter for secretarial assistance and David Robertson for performing the inhibin B assays.

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Grigg, A., McLachlan, R., Zajac, J. et al. Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg). Bone Marrow Transplant 26, 1089–1095 (2000). https://doi.org/10.1038/sj.bmt.1702695

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