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.

  • Correspondence
  • Published:

The impact of low dose busulfan on gonodal function after allogeneic hematopoietic stem cell transplantation for aplastic anemia

Bone Marrow Transplantation volume 55, pages 1169–1171 (2020)Cite this article

Subjects

Gonadal disfunction and infertility are important adverse late effects of allogeneic hematopoietic stem cell transplants (HSCT), especially in children and young adults. It is already known that patients with aplastic anemia transplanted with cyclophosphamide 200 mg/kg, with or without anti-thymocyte globulin (ATG), usually have preserved gonadal function and fertility [1, 2]. Myeloablative doses of busulfan are associated with high rates of gonadal dysfunction, especially in the female adult population [3, 4], but little is known about the effect of reduced busulfan doses on gonadal function. Due to the high cost of ATG and with the aim to circumvent the high rates of graft failure due to an increased frequency of previous alloimmunization in our patients, an alternative conditioning regimen with cyclophosphamide and low dose busulfan has been used in Brazil for many years [5], but patients’ gonadal function and fertility have not been previously evaluated.

We retrospectively evaluated patients younger than 45 years of age with severe aplastic anemia undergoing allogeneic HSCT from January 1991 to December 2013 at the Hospital das Clínicas, Universidade de São Paulo, Brazil receiving a conditioning regimen with oral busulfan 1 mg/Kg/dose every 6 hours, total 4 doses (4 mg/Kg) and cyclophosphamide 50 mg/Kg/day, total 4 doses (200 mg/kg). Graft versus host prophylaxis included standard dose cyclosporine and methotrexate. We included in this analysis patients who were 45 years old or less at the transplant and who had at least 2 years of follow up and we excluded patients who received any other conditioning regimens or who died before two years after transplant. The study was approved by the Ethics Committee of our Institution number 47629015.0.0000.0068.

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

References

  1. Sanders JE, Woolfrey AE, Carpenter PA, Storer BE, Hoffmeister PA, Deeg HJ, et al. Late effects among pediatric patients followed for nearly 4 decades after transplantation for severe aplastic anemia. Blood. 2011;118:1421–8.

    Article  CAS  Google Scholar 

  2. Kröger N, Zabelina T, Renges H, Krüger W, Kordes U, Rischewski J, et al. Long-term follow-up of allogeneic stem cell transplantation in patients with severe aplastic anemia after conditioning with cyclophosphamide plus antithymocyte globulin. Ann Hematol. 2002;81:627–31.

    Article  Google Scholar 

  3. Sanders JE, Hawley J, Levy W, Gooley T, Buckner CD, Deeg HJ, et al. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood. 1996;87:3045–52.

    Article  CAS  Google Scholar 

  4. Borgmann-Staudt A, Rendtorff R, Reinmuth S, Hohmann C, Keil T, Schuster FR, et al. Fertility after allogeneic haematopoietic stem cell transplantation in childhood and adolescence. Bone Marrow Transplant. 2012;47:271–6.

    Article  CAS  Google Scholar 

  5. Dulley FL, Vigorito AC, Aranha FJP, Sturaro D, Ruiz MA, Saboya R, et al. Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection. Bone Marrow Transplant. 2004;33:9–13.

    Article  CAS  Google Scholar 

  6. Dvorak CC, Gracia CR, Sanders JE, Cheng EY, Baker KS, Pulsipher MA, et al. NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: endocrine challenges-thyroid dysfunction, growth impairment, bone health, & reproductive risks. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2011;17:1725–38.

    Article  Google Scholar 

  7. Pfitzer C, Orawa H, Balcerek M, Langer T, Dirksen U, Keslova P, et al. Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study. J Cancer Res Clin Oncol. 2015;141:135–42.

    Article  CAS  Google Scholar 

  8. Panasiuk A, Nussey S, Veys P, Amrolia P, Rao K, Krawczuk-Rybak M, et al. Gonadal function and fertility after stem cell transplantation in childhood: comparison of a reduced intensity conditioning regimen containing melphalan with a myeloablative regimen containing busulfan. Br J Haematol. 2015;170:719–26.

    Article  CAS  Google Scholar 

  9. 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;25:1087–92.

    Article  CAS  Google Scholar 

  10. De Sanctis V, Galimberti M, Lucarelli G, Polchi P, Ruggiero L, Vullo C. Gonadal function after allogenic bone marrow transplantation for thalassaemia. Arch Dis Child. 1991;66:517–20.

    Article  Google Scholar 

  11. Grigg AP, McLachlan R, Zaja J, Szer J. Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg). Bone Marrow Transplant. 2000;26:1089–95.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Bone Marrow Transplantation - Hospital Israelita Albert Einstein, Sao Paulo, Brazil

    Mariana Nassif Kerbauy

  2. Serviço de Hematologia, Hemoterapia e Terapia Celular – Hospital das Clínicas - Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil

    Livia Mariano & Vanderson Rocha

  3. Pediatric Bone Marrow Transplantation - Hospital Samaritano, Sao Paulo, Brazil

    Adriana Seber

  4. Department of Hematology, Churchill Hospital, Oxford University Hospitals, Oxford, UK

    Vanderson Rocha

Authors
  1. Mariana Nassif Kerbauy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Livia Mariano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adriana Seber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vanderson Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Livia Mariano.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kerbauy, M.N., Mariano, L., Seber, A. et al. The impact of low dose busulfan on gonodal function after allogeneic hematopoietic stem cell transplantation for aplastic anemia. Bone Marrow Transplant 55, 1169–1171 (2020). https://doi.org/10.1038/s41409-019-0639-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-019-0639-5

This article is cited by

Search

Advanced search

Quick links