Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Szentágothai Research Centre, University of Pécs, Pécs, Hungary.
PLoS One. 2020 Dec 3;15(12):e0243045. doi: 10.1371/journal.pone.0243045. eCollection 2020.
The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the therapy of chronic myeloid leukemia (CML). Although the efficacy of TKIs is beyond dispute, conception-related safety issues are still waiting to be explored, particularly in males. This systematic review aimed to summarize all available evidence on pregnancy outcomes of female spouses of male CML patients who fathered children after TKI treatment for CML.
We performed a systematic search in seven electronic databases for studies that reported on male CML patients who did or did not discontinue TKI treatment before conceiving, and the pregnancy outcomes of their female spouse are available. The search centered on the TKI era (from 2001 onward) without any other language or study design restrictions.
Out of a total of 38 potentially eligible papers, 27 non-overlapping study cohorts were analyzed. All were descriptive studies (case or case series studies). Altogether, 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. A total of ten offspring with a malformation (2.5%) were reported: six with imatinib (of 313 live births, 1.9%), two with nilotinib (of 26 live births, 7.7%), one with dasatinib (of 43 live births, 2.3%), and none with bosutinib (of 12 live births). Data on CML status were scarcely reported. Only nine pregnancies (from nine males) and no malformation were reported in males who discontinued TKI treatment before conception.
Malformations affected, on average 2.5% of live births from fathers who did not discontinue TKI treatment before conception, which is comparable with the rate of malformations in the general population. Large-scale studies with representative samples are awaited to confirm our results.
酪氨酸激酶抑制剂（TKI）的引入彻底改变了慢性髓性白血病（CML）的治疗方法。虽然 TKI 的疗效毋庸置疑，但与妊娠相关的安全性问题仍有待探讨，尤其是在男性中。本系统评价旨在总结所有关于接受 TKI 治疗的 CML 男性患者的配偶在妊娠后生育子女的妊娠结局的现有证据。
我们在七个电子数据库中进行了系统检索，以查找报告男性 CML 患者在怀孕前是否停止 TKI 治疗以及其配偶妊娠结局的研究。该检索主要集中在 TKI 时代（2001 年以后），没有任何其他语言或研究设计限制。
在总共 38 篇可能符合条件的论文中，有 27 项不重叠的研究队列进行了分析。所有这些都是描述性研究（病例或病例系列研究）。共有 374 位父亲未停药的 428 例妊娠，其中 400 例（93.5%）以活产结束。总共报告了 10 例畸形儿（2.5%）：6 例与伊马替尼（313 例活产，1.9%）有关，2 例与尼洛替尼（26 例活产，7.7%）有关，1 例与达沙替尼（43 例活产，2.3%）有关，1 例与博舒替尼（12 例活产，0%）无关。关于 CML 状态的数据报告甚少。只有 9 例妊娠（来自 9 位男性）和 9 位男性停药前受孕的男性未报告畸形。
未停药前受孕的父亲的活产儿中，畸形儿的平均发病率为 2.5%，与普通人群的畸形儿发病率相当。需要进行大规模、有代表性样本的研究来证实我们的结果。
