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Fertility and pregnancy in chronic myeloid leukemia: real-world experience from an Indian tertiary care institution

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Abstract

Chronic myeloid leukemia (CML) management during pregnancy is challenging. In this retrospective study, hospital records of CML patients treated between 2000 and 2021 were screened to identify patients who tried to conceive/got pregnant (planned and unplanned) on TKIs (tyrosine kinase inhibitors)/were pregnant at CML onset/fathered a child. We found ninety-three pregnancies involving thirty-three women and thirty-eight men, and they were analyzed for the pregnancy outcomes and the strategies utilized for CML management during pregnancy and the pre-conception period. There were two women and four men with primary infertility and five women with secondary infertility. TKIs were discontinued before conception in four planned pregnancies and at the time of recognition of pregnancy in unplanned pregnancies (n = 21). Unplanned pregnancy outcomes were two miscarriages, eight elective terminations, and eleven live births. Planned pregnancies led to four healthy babies. Outcomes of pregnancies at CML onset (n = 17) were six live births, one stillbirth, five elective terminations, and five abortions. Except for one child with congenital micro-ophthalmia, no other child born to the women on TKI had any malformations. Thirty-eight men fathered 51 healthy children. All but two patients (one planned and one unplanned pregnancy) lost their hematological responses during pregnancy and gained their previous best response after restarting TKI. In women who were pregnant at CML onset, complete cytological remission (CCYR) was achieved between 7 and 24 months (median:14 months) after starting TKI. During pregnancy, intermittent hydroxyurea ± TKI (in the second and third trimesters) was used to keep WBCs less than 30,000/mm3. Outcomes of pregnancies in CML patients can be optimized with our approach. TKIs (Imatinib and Nilotinib) can be safely used in the second and third trimesters. Delayed initiation or interruption of TKI during pregnancy does not negatively affect response to TKIs.

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Data Availability

The data analyzed in the current study are available from the corresponding author upon reasonable request.

References

  1. Abruzzese E, Mauro M, Apperley J et al (2020) Tyrosine kinase inhibitors and pregnancy in chronic myeloid leukemia: opinion, evidence, and recommendations. Ther Adv Hematol 11:2040620720966120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ganesan P, Kumar L (2017) Chronic Myeloid Leukemia in India. J Glob Oncol 3:64–71

    Article  PubMed  Google Scholar 

  3. Apperley J (2009) Issues of imatinib and pregnancy outcome. J Natl Compr Canc Netw 7:1050–1058

    Article  CAS  PubMed  Google Scholar 

  4. Pye SM, Cortes J, Ault P et al (2008) The effects of imatinib on pregnancy outcome. Blood 111:5505–5508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cortes JE, Abruzzese E, Chelysheva E et al (2015) The impact of dasatinib on pregnancy outcomes. Am J Hematol 90:1111–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rios SJ, Martínez-Montesinos L, Aroca C et al (2020) Successful ovarian stimulation and pregnancy in an infertile woman with chronic myeloid leukemia. J Assist Reprod Genet 37:2473–2476

    Article  PubMed  PubMed Central  Google Scholar 

  7. Salem W, Li K, Krapp C et al (2019) Imatinib treatments have long-term impact on placentation and embryo survival. Sci Rep 9:2535

    Article  PubMed  PubMed Central  Google Scholar 

  8. Salem W, Ho JR, Woo I et al (2020) Long-term imatinib diminishes ovarian reserve and impacts embryo quality. J Assist Reprod Genet 37:1459–1466

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zamah AM, Mauro MJ, Druker BJ et al (2011) Will imatinib compromise reproductive capacity. Oncologist 16:1422–1427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Abruzzese E, Turkina AG, Apperley JF et al (2019) Pregnancy management in CML patients: to treat or not to treat? Report of 224 outcomes of the European Leukemia Net (ELN) database. Blood 13(134):498

    Article  Google Scholar 

  11. Madabhavi I, Sarkar M, Modi M et al (2019) Pregnancy outcomes in chronic myeloid leukemia: a single center experience. J Glob Oncol 5:1–11

    PubMed  Google Scholar 

  12. Assi R, Kantarjian H, Keating M et al (2021) Management of chronic myeloid leukemia during pregnancy among patients treated with a tyrosine kinase inhibitor: a single-Center experience. Leuk Lymphoma 62:909–917

    Article  CAS  PubMed  Google Scholar 

  13. Wang DP, Liang MY, Zhang XH, Wang SM (2010) Clinical analysis about the management and the perinatal outcomes of pregnancy with chronic myeloid leukemia. Zhonghua Fu Chan Ke Za Zhi 45:735–739

    PubMed  Google Scholar 

  14. Dou X, Qin Y, Huang X, Jiang Q (2019) Planned Pregnancy in Female Patients with Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitor Therapy. Oncologist 24:e1141–e1147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Iqbal J, Ali Z, Khan AU, Aziz Z (2014) Pregnancy outcomes in patients with chronic myeloid leukemia treated with imatinib mesylate: short report from a developing country. Leuk Lymphoma 55:2109–2113

    Article  CAS  PubMed  Google Scholar 

  16. Merante S, Orlandi E, Bernasconi P et al (2005) Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation. Haematologica 90:979–981

    PubMed  Google Scholar 

  17. Abruzzese E, Aureli S, Bondanini F et al (2022) Chronic Myeloid Leukemia and Pregnancy: When Dreams Meet Reality. State of the Art, Management and Outcome of 41 Cases Nilotinib Placental Transfer. J Clin Med 11:1801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hochhaus A, Baccarani M, Silver RT et al (2020) European Leukemia Net 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34:966–984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee J-O, Kim D-W, Abruzzese E et al (2018) Kinetics of BCR-ABL after TKI Interruption during Pregnancy in CML: A Multinational Retrospective Analysis. Blood 132(Supplement 1):4263

    Article  Google Scholar 

  20. Patki A, Chauhan N (2016) An Epidemiology Study to Determine the Prevalence and Risk Factors Associated with Recurrent Spontaneous Miscarriage in India. J Obstet Gynaecol India 66:310–315

    Article  CAS  PubMed  Google Scholar 

  21. Peng B, Lloyd P, Schran H (2005) Clinical Pharmacokinetics of Imatinib. Clin Pharmacokinet 44(9):879–894

    Article  CAS  PubMed  Google Scholar 

  22. Garnock-Jones KP (2011) Nilotinib: in the first-line treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid Leukaemia in chronic phase. Drugs 71(12):1579–1590

    Article  CAS  PubMed  Google Scholar 

  23. Christopher LJ, Cui D, Wu C et al (2008) Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos 36(7):1357–1364

    Article  CAS  PubMed  Google Scholar 

  24. Abruzzese E, Elena C, Castagnetti F et al (2018) Gimema Registry of Conception/Pregnancy in Adult Italian Patients Diagnosed with Chronic Myeloid Leukemia (CML): Report on 166 Outcomes. Blood 132(Supplement 1):43

    Article  Google Scholar 

  25. Goh HG, Kim YJ, Kim DW et al (2009) Previous best responses can be re-achieved by resumption after imatinib discontinuation in patients with chronic myeloid leukemia: implication for intermittent imatinib therapy. Leuk Lymphoma 50(6):944–951

    Article  CAS  PubMed  Google Scholar 

  26. Mahon FX, Réa D, Guilhot J et al (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11(11):1029–1035

    Article  CAS  PubMed  Google Scholar 

  27. Alkatan HM, Bedaiwi KM, Al-Faky YH et al (2022) Demographics and histopathological characteristics of enucleated microphthalmic globes. Sci Rep 12:5283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dharmasena A, Keenan T, Goldacre R et al (2017) Trends over time in the incidence of congenital anophthalmia, microphthalmia and orbital malformation in England: database study. Br J Ophthalmol 101:735–739

    Article  PubMed  Google Scholar 

  29. Ramasamy K, Hayden J, Lim Z et al (2007) Successful pregnancies involving men with chronic myeloid leukaemia on imatinib therapy [letter]. Br J Haematol 137(4):374–375

    Article  PubMed  Google Scholar 

  30. Seshadri T, Seymour JF, McArthur GA (2004) Oligospermia in a patient receiving imatinib therapy for the hypereosinophilic syndrome. N Engl J Med 351:2134–2135

    Article  CAS  PubMed  Google Scholar 

  31. Ghalaut VS, Prakash G, Bansal P et al (2014) Effect of imatinib on male reproductive hormones in BCR-ABL positive CML patients: A preliminary report. J Oncol Pharm Pract 20:243–248

    Article  CAS  PubMed  Google Scholar 

  32. Bay K, Bjerrum OW, Olsson-Strömberg U et al (2013) Reproductive hormone profiles during imatinib therapy in men with chronic myeloid leukemia. Andrology 2(105):2167–250

    Google Scholar 

  33. Chang X, Zhou L, Chen X et al (2017) Impact of imatinib on the fertility of male patients with chronic myelogenous leukaemia in the chronic phase. Target Oncol 12(6):827–832

    Article  PubMed  Google Scholar 

  34. Hensley ML, Ford JM (2003) Imatinib treatment: Specific issues related to safety, fertility, and pregnancy. Semin Hematol 1(40):21–25

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, IRCH, All India Institute of Medical Sciences, New Delhi, India

    Chethan R, Prabhat Singh Malik, Ranjit Kumar Sahoo, Surender Sharawat, Mayank Singh, Vikas Garg, Kanupriya Bhatia, Anura Kantak & Lalit Kumar

  2. Department of Gynaecology, All India Institute of Medical Sciences, New Delhi, India

    Sunesh Kumar

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  1. Chethan R
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  2. Prabhat Singh Malik
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  3. Ranjit Kumar Sahoo
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  9. Sunesh Kumar
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Contributions

Lalit Kumar and Chethan R—Designed the study, collection and analysis of the data and writing of the manuscript.

Ranjit Kumar Sahoo and Prabhat.S. Malik, Sunesh Kumar—Clinical management and review of manuscript.

Surender Sharawat, Mayank Singh: Performed cytogenetics and RT-PCR.

Vikas Garg, Kanupriya Bhatia—Data collection and writing of manuscript.

Anura Kantak—Data collection.

All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Lalit Kumar.

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Institution review board approved the study.

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Informed consent waiver was granted by the IRB as it was a retrospective study.

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The authors declare no competing interests.

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R, C., Malik, P.S., Sahoo, R.K. et al. Fertility and pregnancy in chronic myeloid leukemia: real-world experience from an Indian tertiary care institution. Ann Hematol 102, 2087–2096 (2023). https://doi.org/10.1007/s00277-023-05280-9

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  • DOI: https://doi.org/10.1007/s00277-023-05280-9

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