Targeted Oncology

, Volume 12, Issue 6, pp 827–832 | Cite as

Impact of Imatinib on the Fertility of Male Patients with Chronic Myelogenous Leukaemia in the Chronic Phase

Short Communication
  • 144 Downloads

Abstract

Background

Imatinib is a first-line tyrosine kinase inhibitor for treating chronic myelogenous leukaemia (CML) and has greatly improved the prognosis of this disease. An increasing number of CML patients of reproductive age are diagnosed each year, and the impact of imatinib on fertility is a major concern. Providing useful advice to these patients regarding the choice of their therapeutic treatment is very important.

Objective

This study examined the impact of imatinib on the fertility of male patients with CML in the chronic phase.

Patients and Methods

We performed a study of 48 adult male CML patients in the chronic phase (CML-CP), 50 healthy control subjects, and 10 male patients with infertility. Imatinib levels in semen and plasma were measured using high-performance liquid chromatography/mass spectrometry. We examined the effects of imatinib on sperm parameters and the male reproductive system using a computer-assisted sperm assay and ultrasound, respectively. We analysed sex hormone levels in the sera of CML-CP patients using an enzyme-linked immunosorbent assay.

Results

Imatinib levels in semen were comparable to plasma levels in CML-CP patients. CML-CP patients treated with imatinib exhibited reduced sperm density, counts, survival rates, and activity. Ultrasound demonstrated that the shape and size of the testis and epididymis in CML-CP patients undergoing imatinib treatment were normal. However, 19 of these patients exhibited a hydrocele in their tunica vaginalis, with a large dark area of effusion (0.7–2.9 cm in width). Sex hormone levels in the sera of the CML-CP patients were normal.

Conclusions

These results suggest that imatinib crosses the blood-testis barrier and reduces sperm density, sperm count, survival rates, and activity in CML-CP patients. However, imatinib did not affect the structure of reproductive organs or sex hormone levels.

Notes

Compliance with Ethical Standards

Funding

This study was supported by a grant from the National Nature Science Foundation of Liaoning Province (number: 2,015,020,411–301).

Conflict of Interest

The authors declare no conflicts of interest.

References

  1. 1.
    Rowley JD. A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa Staining. Nature. 1973;243:290–3.CrossRefPubMedGoogle Scholar
  2. 2.
    Avilésvázquez S, Chávezgonzález A, Mayani H. Tyrosine kinase inhibitors (TKI): a new revolution in the treatment of chronic myeloid leukemia (CML). Gac Med Mex. 2013;149(6):646–54.Google Scholar
  3. 3.
    Miura M. Therapeutic drug monitoring of Imatinib, Nilotinib, and Dasatinib for patients with chronic myeloid leukemia. Biol Pharm Bull. 2015;38(5):645–54.CrossRefPubMedGoogle Scholar
  4. 4.
    Sacha T. Imatinib in chronic myeloid leukemia: an overview. Mediterr J Hematol Infect Dis. 2014;6(1):e2014007.Google Scholar
  5. 5.
    Mendizabal AM, Garciagonzalez P, Levine PH. Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries. Cancer Epidemiol. 2013;37(3):247–54.CrossRefPubMedGoogle Scholar
  6. 6.
    Wang J, Shen ZX, Saglio G, et al. Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina. Blood. 2015;125(18):2771–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Esteves SC, Zini A, Aziz N, et al. Critical appraisal of World Health Organization’s new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology. 2012;79(1):16–22.CrossRefPubMedGoogle Scholar
  8. 8.
    Fava C, Rege-Cambrin G, Saglio G. The choice of first-line chronic myelogenous leukemia treatment. Ann Hematol. 2015;94(2):S123–31.Google Scholar
  9. 9.
    Jabbour EJ, Cortes JE, Kantarjian HM. Tyrosine kinase inhibition: a therapeutic target for the management of chronic-phase chronic myeloid leukemia. Expert Rev Anticancer Ther. 2013;13(12):1433–52.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Apperley J. CML in pregnancy and childhood. Best Pract Res Clin Haematol. 2009;22(3):455–74.CrossRefPubMedGoogle Scholar
  11. 11.
    XiaoHui C, Huai G, Yang X. Imatinib effects on fertility and reproductive in patients with chronic myelogenous leukemia (in Chinese, review). Carcinog Teratog Mutagen. 2010;22(6):477–9.Google Scholar
  12. 12.
    Steegmann JL, Baccarani M, Breccia M, et al. European leukemia net recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30(8):1648–71.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Prasad AM, Ramnarayan K, Nalini K, et al. Effect of imatinib on the biochemical parameters of the reproductive function in male Swiss albino mice. Indian J Pharm. 2011;43(4):389–92.CrossRefGoogle Scholar
  14. 14.
    Seshadri T, Seymour JF, McArthur GA. Oligospermia in a patient receiving imatinib therapy for the hypereosinophilic syndrome. N Engl J Med. 2004;351(20):2134–5.Google Scholar
  15. 15.
    Mariani S, Basciani S, Fabbri A, et al. Severe oligozoospermia in a young man with chronic myeloid leukemia on long-term treatment with imatinib started before puberty. Fertil Steril. 2011;95(3):e15–7.CrossRefGoogle Scholar
  16. 16.
    Nurmio M, Toppari J, Zaman F, et al. Inhibition of tyrosine kinases PDGFR and C-kit by imatinib mesylate interferes with postnatal testicular development in the rat. Int J Androl. 2007;30(4):366–76.CrossRefPubMedGoogle Scholar
  17. 17.
    Nurmio M, Kallio J, Toppari J, et al. Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c-kit and PDGFR, in the rat testis. Reprod Toxicol. 2008;25(4):442–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Heim C, Minniear K, Dann CT. Imatinib has deleterious effects on differentiating spermatogonia while sparing spermatogonial stem cell self renewal. Reprod Toxicol. 2011;31(4):454–63.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Abruzzese E, Trawinska MM, De FP, et al. Management of pregnant chronic myeloid leukemia patients. Expert Rev Hematol. 2016;9(8):781–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Nicolini FE, Alcazer V, Huguet F, et al. CML patients show sperm alterations at diagnosis that are not improved with imatinib treatment. Leuk Res. 2016;48(9):80–3.CrossRefPubMedGoogle Scholar
  21. 21.
    Jain A, Khadwal A, Prakashet G, al. Cytopathological diagnosis of an unusual cause of malignant Hydrocele. Clin Medicine Insights Pathol. 2016;9(9):29–31.Google Scholar
  22. 22.
    Kim H, Chang HM, Ryu MH, et al. Concurrent male Gynecomastia and testicular Hydrocele after Imatinib Mesylate treatment of a gastrointestinal Stromal tumor. J Korean Med Sci. 2005;20(3):512–5.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Seymour JF, Grigg A, Reynolds J, et al. Imatinib’s potential effects on fertility, immunity and pulmonary function: a prospective study in patients with previously untreated CML. Blood. 2004;104(11):1020.Google Scholar
  24. 24.
    Xiaohui C, Huai G, Yubin C, et al. One case report: a male patient with chronic myeloid leukemia treated with imatinib involved in healthy pregnancies [article in Chinese]. Zhong Guo Yi Yao Dao Bao. 2013;10(1):116–7.Google Scholar
  25. 25.
    Mukhopadhyay A, Dasgupta S, Kanti RU, et al. Pregnancy outcome in chronic myeloid leukemia patients on imatinib therapy. Ir J Med Sci. 2015;184(1):183–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Jiang Q, Jiang B, Chen SS, et al. Pregnancy outcome among patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors [article in Chinese]. Zhonghua Xue Ye Xue Za Zhi. 2012;33(1):6–9.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Xiaohui Chang
    • 1
  • Lin Zhou
    • 2
  • Xiaoxia Chen
    • 3
  • Baoli Xu
    • 4
  • Yubin Cheng
    • 1
  • Shujun Sun
    • 1
  • Meiyun Fang
    • 5
  • Yang Xiang
    • 1
  1. 1.Department of HematologyThe 210th Hospital of Chinese People’s Liberation ArmyLiaoningChina
  2. 2.Department of Scientific ResearchThe 210th Hospital of Chinese People’s Liberation ArmyLiaoningChina
  3. 3.Department of PharmacyThe Liaoning University of Traditional Chinese MedicineLiaoningChina
  4. 4.Department of PharmacyThe 210th Hospital of Chinese People’s Liberation ArmyLiaoningChina
  5. 5.Department of Hematology, The First Affiliated HospitalDalian Medical UniversityLiaoningChina

Personalised recommendations