Managing pregnancy in chronic myeloid leukaemia
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Over the past decade, we have witnessed significant advances in knowledge of the biology and treatment of chronic myeloid leukaemia (CML). The development of molecular-targeted therapy with tyrosine kinase inhibitors (TKIs) has fundamentally changed the outcome of this disease. Treatment with TKIs is now the standard of care in patients with CML and has dramatically improved long-term survival in the majority of patients. Patients who achieve major molecular response (MMR) after 2 years of treatment with imatinib have survival rates comparable to those of the general population. The success of TKIs has led to durable molecular response and possibility of normal life expectancies, such that it is now timely to address quality of life aspects such as fertility, pregnancy and family planning. Pregnancy in CML presents specific management and therapeutic challenges for the patient and the physician. Despite the recent treatment advances, we still have limited data on the safety of TKIs in pregnancy and its effect on fertility. However, there is a cause for concern and heightened awareness following the occurrence of a constellation of rare congenital malformations and spontaneous abortions in association with imatinib therapy. When a patient becomes pregnant whilst receiving TKI therapy, the difficulty lies in balancing the risk to the foetus of continuing therapy versus the risk to the patient of treatment interruption and potentially losing optimal disease response. All couples should be counselled on the risks associated with pregnancy whilst receiving TKI therapy. This is an essential aspect in patient care and frequently not emphasized enough by physicians. At the time of diagnosis, fertility preservation should be discussed with both male and female patients of childbearing potential. They should be made aware of fertility options which are available such as semen cryopreservation, ovarian or oocyte retrieval and storage and embryo cryopreservation in view of the potential detrimental effect of TKIs on fertility and gonadal function. The recommendation given to patients planning pregnancy differs according to their disease response to TKI therapy, which is the most important prognostic factor in CML.
KeywordsFertility Pregnancy Chronic myeloid leukaemia Tyrosine kinase inhibitors
RP, DM and JFA are grateful to the National Institute of Health Research (NIHR) and the NIHR Biomedical Research Centre for the financial support.
RP, DM and JFA performed the literature review and wrote the manuscript.
Conflict of interest
Authors declare no conflict of interest with regard to this paper.
- 1.Mahon FX, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P (2010) Intergroupe Français des Leucémies Myéloïdes Chroniques. 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):1029–1035CrossRefPubMedGoogle Scholar
- 2.Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT, Dang P, Goyne JM, Slader C, Filshie RJ, Mills AK, Melo JV, White DL, Grigg AP, Hughes TP (2013) Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood 122(4):515–522CrossRefPubMedGoogle Scholar
- 3.(2014) Gleevec (imatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals CorporationGoogle Scholar
- 4.(2014) Sprycel (dasatinib): prescribing information. Princeton, NJ: Bristol-Myers Squibb CompanyGoogle Scholar
- 5.(2014) Tasigna (nilotinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals CorporationGoogle Scholar
- 7.(2013) Bosulif (bosutinib) [prescribing information]. New York, NY: Pfizer IncGoogle Scholar
- 8.(2014) Inclusig (ponatinib) [prescribing information]. Cambridge, MA: Ariad Pharmaceuticals, IncGoogle Scholar
- 13.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 LymphomaGoogle Scholar
- 15.Cortes J, O’Brien S, Ault P, Borthakur G, Jabbour E, Bradley-Garelik B, Debreczeni K, Yang D, Liu D, Kantarjian H (2008) Pregnancy outcomes among patients with chronic myeloid leukemia treated with dasatinib. Blood 112(11). Abstract 3230: Poster presented at: the 50th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2008; San Francisco, USAGoogle Scholar
- 22.Bleyl SB, Moshrefi A, Shaw GM, Saijoh Y, Schoenwolf GC, Pennacchio LA, Slavotinek AM (2007) Candidate genes for congenital diaphragmatic hernia from animal models: sequencing of FOG2 and PDGFR alpha reveals rare variants in diaphragmatic hernia patients. Eur J Hum Genet 15:950–958CrossRefPubMedGoogle Scholar
- 24.Bayraktar S, Morency B, Escalon MP (2010) Successful pregnancy in a patient with chronic myeloid leukaemia exposed to dasatinib during the first trimester. BMJ Case Reports Online PublicationGoogle Scholar
- 27.Dine G, Levert M, Rehn Y, Ali AN, Brahimi S, Gaillard B, Bocq I, Fumagalli G (2013) Two successful successive pregnancies in a woman with CML treated with dasatinib and temporary peg-interferon. J US-China Med Sci 10(5–6):128–133Google Scholar
- 29.Conchon M, Sanabani SS, Bendit I (2009) Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study. J Hematol Oncol 42(2)Google Scholar
- 30.Etienne G, Milpied B, Réa D, Rigal-Huguet F, Tulliez M, Nicolini FE (2010) French Intergroup of CML (Fi-LMC group). Guidelines for the management of nilotinib (Tasigna)-induced side effects in chronic myelogenous leukemia: recommendations of French Intergroup of CML (Fi-LMC group). Bull Cancer 97(8):997–1009PubMedGoogle Scholar
- 31.Goh HG, Kim YJ, Kim DW, Kim HJ, Kim SH, Jang SE, Lee J, Kim D, Kim WS, Park SH, Kweon IY (2009) Previous best responses can be re-achieved by resumption after imatinib discontinuation in patients with chronic myeloid leukaemia: implications for intermittent imatinib therapy. Leuk Lymphoma 50(6):944–951CrossRefPubMedGoogle Scholar
- 32.Kuwabara A, Babb A, Ibrahim A, Milojkovic D, Apperley J, Bua M, Reid A, Foroni L, Rezvani K, Goldman J, Marin D (2010) Poor outcome after reintroduction of imatinib in patients with CML who interrupt therapy on account of pregnancy without having achieved an optimal response. Blood 116(6):1014–1016CrossRefPubMedCentralPubMedGoogle Scholar
- 44.(2006) Bristol-Myers Squibb Canada. HYDREA® product monograph. Montreal, QuebecGoogle Scholar
- 46.Lichtman MLJ (2001) 6th ed. Vol. 1047. New York, NY: McGraw-Hill. Acute myelogenous leukemia. Williams HematologyGoogle Scholar