Skip to main content
SpringerLink
Log in

A new method for evaluating the risk of transferring leukemic cells with transplanted cryopreserved ovarian tissue

  • Fertility Preservation
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

This study aimed to develop a method to detect ovarian residual disease by multicolor flow cytometry in acute leukemia patients.

Methods

We designed an experimental model consisting in adding acute leukemia cells to a cell suspension obtained from healthy ovarian cortex. Leukemic cell detection within the ovarian cell suspension required the development of a specific myeloid antibody panel different from that commonly used for minimal residual disease (MRD) monitoring in bone marrow. The method was then used to detect ovarian residual disease in 11 acute leukemia patients.

Results

Multicolor flow cytometry is able to evaluate the presence of viable leukemic cells in the ovarian cortex with good specificity and robust sensitivity of 10−4. We observed a good correlation between multicolor flow cytometry and quantitative polymerase chain reaction results. Ovarian residual disease detection by multicolor flow cytometry was positive in 3 out of 11 acute leukemia patients.

Conclusion

Multicolor flow cytometry can potentially be applied to ovarian tissue from all acute leukemia patients and is essential to evaluate the risk of cancer re-seeding before autograft of ovarian tissue in case of acute leukemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Howlader N, Noone A, Krapcho M, Neyman N, Aminou R, Altekruse S et al. SEER Cancer Statistics review, 1975-2010. National Cancer Institute. 2013.

  2. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, et al. Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report. Human Reprod (Oxford, England). 2006;21(1):183–8.

    Article  CAS  Google Scholar 

  3. Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol. 2000;169(1–2):123–31.

    Article  CAS  PubMed  Google Scholar 

  4. Wallace WH, Anderson RA, Irvine DS. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol. 2005;6(4):209–18. doi:10.1016/s1470-2045(05)70092-9.

    Article  PubMed  Google Scholar 

  5. Donnez J, Dolmans MM. Fertility preservation in women. Nat Rev Endocrinol. 2013;9(12):735–49. doi:10.1038/nrendo.2013.205.

    Article  CAS  PubMed  Google Scholar 

  6. Donnez J, Dolmans MM. Ovarian tissue freezing: current status. Curr Opin Obstet Gynecol. 2015. doi:10.1097/gco.0000000000000171.

    PubMed  Google Scholar 

  7. Bastings L, Beerendonk CC, Westphal JR, Massuger LF, Kaal SE, van Leeuwen FE, et al. Autotransplantation of cryopreserved ovarian tissue in cancer survivors and the risk of reintroducing malignancy: a systematic review. Hum Reprod Update. 2013;19(5):483–506. doi:10.1093/humupd/dmt020.

    Article  CAS  PubMed  Google Scholar 

  8. Cave H, van der Werff ten Bosch J, Suciu S, Guidal C, Waterkeyn C, Otten J, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer—Childhood Leukemia Cooperative Group. N Engl J Med. 1998;339(9):591–8.

    Article  CAS  PubMed  Google Scholar 

  9. Campana D, Coustan-Smith E. Detection of minimal residual disease in acute leukemia by flow cytometry. Cytometry. 1999;38(4):139–52.

    Article  CAS  PubMed  Google Scholar 

  10. Greve T, Clasen-Linde E, Andersen MT, Andersen MK, Sorensen SD, Rosendahl M, et al. Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells. Blood. 2012;120(22):4311–6. doi:10.1182/blood-2012-01-403022.

    Article  CAS  PubMed  Google Scholar 

  11. Rosendahl M, Andersen MT, Ralfkiaer E, Kjeldsen L, Andersen MK, Andersen CY. Evidence of residual disease in cryopreserved ovarian cortex from female patients with leukemia. Fertil Steril. 2010;94(6):2186–90. doi:10.1016/j.fertnstert.2009.11.032.

    Article  PubMed  Google Scholar 

  12. Dolmans MM, Marinescu C, Saussoy P, Van Langendonckt A, Amorim C, Donnez J. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood. 2010;116(16):2908–14. doi:10.1182/blood-2010-01-265751.

    Article  CAS  PubMed  Google Scholar 

  13. Amiot C, Angelot-Delettre F, Zver T, Alvergnas-Vieille M, Saas P, Garnache-Ottou F, et al. Minimal residual disease detection of leukemic cells in ovarian cortex by eight-color flow cytometry. Human Reprod (Oxford, England). 2013;28(8):2157–67. doi:10.1093/humrep/det126.

    Article  CAS  Google Scholar 

  14. Zver T, Alvergnas-Vieille M, Garnache-Ottou F, Ferrand C, Roux C, Amiot C. Minimal residual disease detection in cryopreserved ovarian tissue by multicolor flow cytometry in acute myeloid leukemia. Haematologica. 2014;99(12):e249–52. doi:10.3324/haematol.2014.113373.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Chian RC, Uzelac PS, Nargund G. In vitro maturation of human immature oocytes for fertility preservation. Fertil Steril. 2013;99(5):1173–81. doi:10.1016/j.fertnstert.2013.01.141.

    Article  CAS  PubMed  Google Scholar 

  16. Luyckx V, Dolmans MM, Vanacker J, Legat C, Fortuno Moya C, Donnez J, et al. A new step toward the artificial ovary: survival and proliferation of isolated murine follicles after autologous transplantation in a fibrin scaffold. Fertil Steril. 2014;101(4):1149–56. doi:10.1016/j.fertnstert.2013.12.025.

    Article  PubMed  Google Scholar 

  17. Luyckx V, Dolmans MM, Vanacker J, Scalercio SR, Donnez J, Amorim CA. First step in developing a 3D biodegradable fibrin scaffold for an artificial ovary. J Ovarian Res. 2013;6(1):83. doi:10.1186/1757-2215-6-83.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Christine Decanter and Brigitte Leroy-Martin (CHRU Lille, France), Catherine POIROT (CHI Poissy Saint-Germain, France) and Nathalie Rives (CHU Rouen, France) for their help in ovarian tissue collection and Joanna Farrow for editorial assistance. This work was supported by the Regional University Hospital of Besançon, DGOS/INSERM/INCa, the Committee of the League against Cancer, and the Regional Council of Franche-Comté.

Author information

Authors and Affiliations

  1. INSERM U 1098, CIC1431, 8, rue du Docteur Jean-François-Xavier GIROD, F-25020, Besançon Cedex, France

    Tristan Zver, Magalie Alvergnas-Vieille, Francine Garnache-Ottou, Christophe Roux & Clotilde Amiot

  2. Université de Franche-Comté, SFR FED4234, F-25000, Besançon Cedex, France

    Francine Garnache-Ottou, Christophe Roux & Clotilde Amiot

  3. CHRU Besançon, Service de Biologie et Médecine de la Reproduction, Cryobiologie-CECOS Franche-Comté Bourgogne, 3 Bd A Fleming, F-25030, Besançon Cedex, France

    Tristan Zver, Magalie Alvergnas-Vieille, Christophe Roux & Clotilde Amiot

  4. EFS Bourgogne Franche-Comté, F-25020, Besançon Cedex, France

    Francine Garnache-Ottou

Authors
  1. Tristan Zver
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magalie Alvergnas-Vieille
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francine Garnache-Ottou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christophe Roux
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clotilde Amiot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tristan Zver.

Additional information

Capsule

Ovarian residual disease detection by multicolor flow cytometry was positive for 3 of 11 acute leukemia patients. The safety of crypreserved ovarian tissue autograft in case of acute leukemia remains of great concern.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zver, T., Alvergnas-Vieille, M., Garnache-Ottou, F. et al. A new method for evaluating the risk of transferring leukemic cells with transplanted cryopreserved ovarian tissue. J Assist Reprod Genet 32, 1263–1266 (2015). https://doi.org/10.1007/s10815-015-0512-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-015-0512-4

Keywords

Search

Navigation