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Feasibility of ovarian stimulation for fertility preservation during and after blinatumomab treatment for Ph-negative B-cell acute lymphoblastic leukemia

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Abstract

It is challenging to preserve the fertility of female patients with B-cell acute lymphoblastic leukemia (B-ALL) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) while maintaining treatment intensity. We report two cases of female patients with Philadelphia chromosome-negative (Ph -) B-ALL whose oocytes were retrieved after controlled ovarian stimulation during and after blinatumomab treatment. The first patient was a 30-year-old woman with relapsed Ph-B-ALL who received prednisolone (PSL) and cytoreductive chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone, followed by three courses of blinatumomab bridging to allo-HSCT. Ovarian stimulation was performed twice during blinatumomab administration, and two oocytes were retrieved during each course. The second patient was a 26-year-old woman with newly diagnosed Ph-B-ALL who received PSL, one course of conventional chemotherapy, and one course of high-dose methotrexate and cytarabine followed by two courses of blinatumomab bridging to allo-HSCT. Immediately after completion of the first course of blinatumomab, ovarian stimulation was performed, and three oocytes were retrieved. Use of a 2-week rest period enabled ovarian stimulation and oocyte retrieval to be performed without delaying treatment. Blinatumomab may be an option for preserving fertility while maintaining treatment intensity.

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References

  1. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69(5):363–85.

    Article  PubMed  Google Scholar 

  2. Hammond C, Abrams JR, Syrjala KL. Fertility and risk factors for elevated infertility concern in 10-year hematopoietic cell transplant survivors and case-matched controls. J Clin Oncol. 2007;25(23):3511–7.

    Article  PubMed  Google Scholar 

  3. Chiodi S, Spinelli S, Ravera G, Petti AR, Van Lint MT, Lamparelli T, et al. Quality of life in 244 recipients of allogeneic bone marrow transplantation. Br J Haematol. 2000;110(3):614–9.

    Article  CAS  PubMed  Google Scholar 

  4. Watson M, Wheatley K, Harrison GA, Zittoun R, Gray RG, Goldstone AH, et al. Severe adverse impact on sexual functioning and fertility of bone marrow transplantation, either allogeneic or autologous, compared with consolidation chemotherapy alone: analysis of the MRC AML 10 trial. Cancer. 1999;86(7):1231–9.

    Article  CAS  PubMed  Google Scholar 

  5. Carter A, Robison LL, Francisco L, Smith D, Grant M, Baker KS, et al. Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study. Bone Marrow Transplant. 2006;37(11):1023–9.

    Article  CAS  PubMed  Google Scholar 

  6. Rossi BV, Missmer S, Correia KF, Wadleigh M, Ginsburg ES. Ovarian reserve in women treated for acute lymphocytic leukemia or acute myeloid leukemia with chemotherapy but not stem cell transplantation. ISRN Oncol. 2012;2012:956190.

    PubMed  PubMed Central  Google Scholar 

  7. Chan JL, Johnson LN, Efymow BL, Sammel MD, Gracia CR. Outcomes of ovarian stimulation after treatment with chemotherapy. J Assist Reprod Genet. 2015;32(10):1537–45.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2009;27(16):2677–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gracia CR, Sammel MD, Freeman E, Prewitt M, Carlson C, Ray A, et al. Impact of cancer therapies on ovarian reserve. Fertil Steril. 2012;97(1):134–40.

    Article  PubMed  Google Scholar 

  10. Ben-Aharon I, Shalgi R. What lies behind chemotherapy-induced ovarian toxicity? Reproduction. 2012;144(2):153–63.

    Article  CAS  PubMed  Google Scholar 

  11. Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011;317(9):1255–60.

    Article  CAS  PubMed  Google Scholar 

  12. Apel A, Ofran Y, Wolach O, Shimony S, Ram R, Levi I, et al. Safety and efficacy of blinatumomab: a real world data. Ann Hematol. 2020;99(4):835–8.

    Article  CAS  PubMed  Google Scholar 

  13. Jung SH, Lee SR, Yang DH, Lee S, Yoon JH, Lee H, et al. Efficacy and safety of blinatumomab treatment in adult Korean patients with relapsed/refractory acute lymphoblastic leukemia on behalf of the Korean Society of Hematology ALL Working Party. Ann Hematol. 2019;98(1):151–8.

    Article  CAS  PubMed  Google Scholar 

  14. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dolmans MM, Donnez J. Fertility preservation in women for medical and social reasons: oocytes vs ovarian tissue. Best Pract Res Clin Obstet Gynaecol. 2021;70:63–80.

    Article  PubMed  Google Scholar 

  16. Salama M, Anazodo A, Woodruff TK. Preserving fertility in female patients with hematological malignancies: a multidisciplinary oncofertility approach. Ann Oncol. 2019;30(11):1760–75.

    Article  CAS  PubMed  Google Scholar 

  17. Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(19):1994–2001.

    Article  PubMed  Google Scholar 

  18. Rosendahl M, Andersen MT, Ralfkiær 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.

    Article  PubMed  Google Scholar 

  19. Dolmans MM, Luyckx V, Donnez J, Andersen CY, Greve T. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue. Fertil Steril. 2013;99(6):1514–22.

    Article  PubMed  Google Scholar 

  20. Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update. 2004;10(3):251–66.

    Article  PubMed  Google Scholar 

  21. Dolmans MM, Amorim CA. Fertility preservation: construction and use of artificial ovaries. Reproduction. 2019;158(5):F15–25.

    Article  CAS  PubMed  Google Scholar 

  22. Blumenfeld Z. Fertility preservation using GnRH agonists: Rationale, possible mechanisms, and explanation of controversy. Clin Med Insights Reprod Health. 2019;13:1179558119870163.

    PubMed  PubMed Central  Google Scholar 

  23. Sönmezer M, Türkçüoğlu I, Coşkun U, Oktay K. Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles. Fertil Steril. 2011;95(6):2125.e9-11.

    Article  CAS  Google Scholar 

  24. Topp MS, Gökbuget N, Stein AS, Zugmaier G, O’Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66.

    Article  CAS  PubMed  Google Scholar 

  25. 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(7):3045–52.

    Article  CAS  PubMed  Google Scholar 

  26. Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation and “burnout”; AS101 prevents follicle loss and preserves fertility. Sci Transl Med. 2013;5(185):185ra62.

    Article  PubMed  CAS  Google Scholar 

  27. Bukulmez O, Arici A. Leukocytes in ovarian function. Hum Reprod Update. 2000;6(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  28. Brannstrom M, Pascoe V, Norman RJ, McClure N. Localization of leukocyte subsets in the follicle wall and in the corpus luteum throughout the human menstrual cycle. Fertil Steril. 1994;61(3):488–95.

    Article  CAS  PubMed  Google Scholar 

  29. Das G, Damotte V, Gelfand JM, Bevan C, Cree BAC, Do L, et al. Rituximab before and during pregnancy: a systematic review, and a case series in MS and NMOSD. Neurol Neuroimmunol Neuroinflamm. 2018;5(3):453.

    Article  Google Scholar 

  30. Asada Y, Morimoto Y, Nakaoka Y, Yamasaki T, Suehiro Y, Sugimoto H, et al. Age-specific serum anti-Müllerian hormone concentration in Japanese women and its usefulness as a predictor of the ovarian response. Reprod Med Biol. 2017;16(4):364–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lie Fong S, Lugtenburg PJ, Schipper I, Themmen AP, de Jong FH, Sonneveld P, et al. Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies. Hum Reprod. 2008;23(3):674–8.

    Article  CAS  PubMed  Google Scholar 

  32. Senapati S, Morse CB, Sammel MD, Kim J, Mersereau JE, Efymow B, Gracia CR. Fertility preservation in patients with haematological disorders: a retrospective cohort study. Reprod Biomed Online. 2014;28(1):92–8.

    Article  PubMed  Google Scholar 

  33. Arce JC, La Marca A, Mirner Klein B, Nyboe Andersen A, Fleming R. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients. Fertil Steril. 2013;99(6):1644–53.

    Article  CAS  PubMed  Google Scholar 

  34. La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010;16(2):113–30.

    Article  PubMed  CAS  Google Scholar 

  35. Jayaprakasan K, Campbell B, Hopkisson J, Johnson I, Raine-Fenning N. A prospective, comparative analysis of anti-Müllerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation. Fertil Steril. 2010;93(3):855–64.

    Article  CAS  PubMed  Google Scholar 

  36. Lee RK, Wu FS, Lin MH, Lin SY, Hwu YM. The predictability of serum anti-Müllerian level in IVF/ICSI outcomes for patients of advanced reproductive age. Reprod Biol Endocrinol. 2011;9:115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Abruzzese E, Trawinska MM, Perrotti AP, De Fabritiis P. Tyrosine kinase inhibitors and pregnancy. Mediterr J Hematol Infect Dis. 2014;6(1):e2014028.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ault P, Kantarjian H, O’Brien S, Faderl S, Beran M, Rios MB, et al. Pregnancy among patients with chronic myeloid leukemia treated with imatinib. J Clin Oncol. 2006;24(7):1204–8.

    Article  CAS  PubMed  Google Scholar 

  39. Ogawa T, Ogi M, Hirata S. A case of ovarian stimulation for fertility preservation in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia after treatment with dasatinib. J Obstet Gynaecol Res. 2021;47(3):1182–5.

    Article  CAS  PubMed  Google Scholar 

  40. Meirow D, Biederman H, Anderson RA, Wallace WH. Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol. 2010;53(4):727–39.

    Article  PubMed  Google Scholar 

  41. Joshi S, Savani BN, Chow EJ, Gilleece MH, Halter J, Jacobsohn DA, Pidala J, et al. Clinical guide to fertility preservation in hematopoietic cell transplant recipients. Bone Marrow Transplant. 2014;49(4):477–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Graduate School of Medicine, Kyoto University, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Yusuke Tashiro, Junya Kanda, Tomoki Iemura, Tadakazu Kondo, Kouhei Yamashita & Akifumi Takaori-Kondo

  2. Department of Gynecology and Obstetrics, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masumi Sunada & Akihito Horie

Authors
  1. Yusuke Tashiro
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  2. Junya Kanda
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Correspondence to Junya Kanda.

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Tashiro, Y., Kanda, J., Iemura, T. et al. Feasibility of ovarian stimulation for fertility preservation during and after blinatumomab treatment for Ph-negative B-cell acute lymphoblastic leukemia. Int J Hematol 116, 453–458 (2022). https://doi.org/10.1007/s12185-022-03323-x

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