Tyrosine Kinase Inhibitors and Pregnancy

Abruzzese, Elisabetta; Trawinska, Malgorzata Monika; Fabritiis, Paolo de; Perrotti, Alessio

doi:10.4084/mjhid.2014.028

Cited by 93 publications

(104 citation statements)

References 41 publications

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“…Zhou et al [14] recently reported on the successful pregnancy outcome in the partner of a man on treatment with nilotinib at a dose of 800 mg daily for 31.5 months at the time of conception. The second case was reported by Abruzzese et al [18] in which a 33-year-old male conceived on nilotinib after 40 days of exposure, resulting in the delivery of a healthy offspring.…”

Section: Male Patientsmentioning

confidence: 96%

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Managing pregnancy in chronic myeloid leukaemia

2015

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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.

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Section: Male Patientsmentioning

confidence: 96%

“…More recently, Abruzzese et al [18] summarized the outcome of 167 of a total of 210 pregnancies in women exposed to imatinib. These women were all exposed to imatinib during period of organogenesis (>5 weeks gestation).…”

Section: Female Patientsmentioning

confidence: 99%

Managing pregnancy in chronic myeloid leukaemia

2015

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“…For women with CML, there is strong evidence to suggest that TKIs during pregnancy confer a small increased risk of spontaneous abortions and a significantly increased risk of congenital malformations including bony and renal deformities, and others. [62][63][64] Hence, it is recommended that TKIs be discontinued for pregnancy. Women who become pregnant and discontinue imatinib without achieving a durable major molecular response (MMR) experience poor outcomes, with loss of responsiveness to imatinib upon resumption of drug.…”

Section: Special Consideration: CMLmentioning

confidence: 99%

Fertility issues in patients with hematologic malignancies

Loren

2015

Hematology

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An essential component of a cancer patient's comprehensive care is addressing potential threats to his or her reproductive health. Providers should discuss the risk of infertility with newly diagnosed patients and offer the chance to consult with a reproductive specialist as early as possible. Standard fertility preservation options include embryo or oocyte cryopreservation for women and sperm banking for men; all options for pre-pubertal children are experimental. Patients with hematologic malignancies are a distinct population in whom standard options may present special challenges, and alternative management strategies are being explored. Unique approaches in hematologic malignancy patients include experimental techniques, such as hormonal therapy, referrals to reproductive specialists after cancer treatment, or discontinuation of tyrosine kinase inhibitor therapy in appropriate chronic myelogenous leukemia patients. Importantly, expedited communication between hematologists and reproductive specialists may greatly enhance the quality of care for these patients. Facilitation of referrals will both improve the quality-of-life and expand the prospect of parenthood in survivors. There are ample opportunities to advance the field of oncofertility through additional research, especially in hematologic malignancy patients.

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“…The role of TKI in pregnancy has been riddled with controversies due to potential fetal malformations [6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…Imatinib, a newer category D drug is a tyrosine kinase inhibitor (TKI) which can prolong CP of CML thereby improving the quality of life, short of curative option of stem cell transplantation. TKI in pregnancy have shown fetal abnormalities recently despite contradicting anecdotal reports of favourable outcomes in the past [6][7][8]. Though there is enough information on the use of TKI in pregnant females with CML, surprisingly there is little information on the effects of CML per se on the pregnancy and on the complications encountered both in baby/mother secondary to CML.…”

Section: Introductionmentioning

confidence: 99%

Obstetric Complications and Management in Chronic Myeloid Leukemia

Rohilla

Rai

Yanamandra

et al. 2015

Indian J Hematol Blood Transfus

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Chronic myeloid leukaemia (CML) is amongst the most common haematological malignancies encountered in adults. The younger age of onset and increased incidence of CML in Indians leads to higher chances of encountering it in pregnancy. Pregnancy in CML is a complex situation as first line therapy with tyrosine kinase inhibitors (TKI), is fraught with multiple fetal safety issues. The fetal aspects have been elucidated in literature, but there is scarcity of information on the obstetric outcome per se in presence of CML, excluding the influence of TKI. Obstetric outcomes of 5 pregnancies in four patients with CML are being reported. Literature on interplay of CML and bleeding or thrombotic manifestations is reviewed. The major complications encountered were antepartum (APH) and postpartum haemorrhage (PPH), preterm labour, intrauterine growth retardation and intrauterine fetal death. Patients in the reproductive age group with diagnosis of CML should be carefully counseled regarding the effect of disease and TKI on the maternal-fetal health. Bleeding complications, particularly APH and PPH may be encountered in CML patients. Close coordination of the obstetrician, haematologist, and neonatologist is required in managing these cases successfully. The need for absolute contraception till the remission of disease needs to be emphasized for further pregnancies.

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Tyrosine Kinase Inhibitors and Pregnancy

Cited by 93 publications

References 41 publications

Managing pregnancy in chronic myeloid leukaemia

Managing pregnancy in chronic myeloid leukaemia

Fertility issues in patients with hematologic malignancies

Obstetric Complications and Management in Chronic Myeloid Leukemia

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