Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
Leuk Lymphoma. 2021 Apr;62(4):909-917. doi: 10.1080/10428194.2020.1849672. Epub 2020 Dec 7.
Tyrosine kinase inhibitors (TKIs) are teratogenic. Chronic myeloid leukemia (CML) is increasingly identified in younger patients who wish to conceive, the management of CML during pregnancy is challenging. We reviewed 51 pregnancies involving 37 patients (30 women, 10 with >1 pregnancy and 7 men) who were either diagnosed with CML during pregnancy or receiving TKI at the time of conception. Ten women were involved in >1 pregnancies. Fifteen women were diagnosed with CML during pregnancy: 10 were treated with hydroxyurea ( = 5), interferon-alfa ( = 3), leukapheresis ( = 1), or nilotinib ( = 1). There were 14 (82%) healthy babies born on term including 2 sets of twins, 2 spontaneous miscarriages (12%), and 1 elective abortion (6%). Within 1 month of delivery or abortion, all women started TKI and achieved MR4.5 ( = 6) and MMR ( = 8) within 3-48 months. One patient, treated with interferon during pregnancy, died of blast phase within 2 months. Four of the 14 remaining women later conceived 5 other pregnancies while on TKI (3 unplanned, 2 planned). Twenty-six patients (7 men; 19 women) conceived while on TKI, with a total of 36 pregnancies. Fifteen women had 20 unplanned pregnancies while receiving TKI and discontinued immediately upon recognition of pregnancy. The median time of TKI exposure was 3 weeks (range, 2-11). Five pregnancies ended in miscarriages and 3 in elective abortion. All 7 men fathered 7 full-term healthy babies. Of 20 babies born to men and women (including one set of twins), 1 had minor abnormality. Seven women lost their responses during pregnancy but at the end of pregnancy all but 2 resumed TKI and regained responses. Seven women involved in 9 planned pregnancies discontinued TKI prior to conception for a median of 4 months (range, 1-20); 3 lost responses during pregnancy. Only 5 patients resumed therapy after delivery. Outcomes were 6 full-term healthy babies, one premature, and two miscarriages. Conception among CML patients while on TKI could be uncomplicated. While patients may lose response following treatment interruption, nearly all regain response upon resuming therapy. Therapy during pregnancy is rarely needed.
酪氨酸激酶抑制剂（TKIs）具有致畸性。越来越多的年轻患者被诊断出患有慢性髓性白血病（CML），这些患者希望怀孕，因此 CML 的孕期管理颇具挑战。我们回顾了 51 例妊娠，涉及 37 名患者（30 名女性，10 名患者有>1 次妊娠，7 名男性），这些患者或在妊娠期间被诊断出 CML，或在妊娠时正在接受 TKI 治疗。10 名女性参与了>1 次妊娠。15 名女性在妊娠期间被诊断出 CML：10 名患者接受羟基脲（ = 5）、干扰素-α（ = 3）、白细胞分离术（ = 1）或尼洛替尼（ = 1）治疗。共有 14 名（82%）健康婴儿足月出生，包括 2 对双胞胎、2 例自然流产（12%）和 1 例选择性流产（6%）。在分娩或流产后 1 个月内，所有女性均开始使用 TKI，并在 3-48 个月内达到 MR4.5（ = 6）和 MMR（ = 8）。1 名在孕期接受干扰素治疗的患者在 2 个月内死于急变期。在其余 14 名女性中，有 4 名在接受 TKI 治疗的同时又怀孕了 5 次（3 次为意外怀孕，2 次为计划怀孕）。26 名患者（7 名男性；19 名女性）在接受 TKI 治疗时怀孕，共怀孕 36 次。15 名女性在接受 TKI 治疗时意外怀孕，且在意识到怀孕后立即停止 TKI 治疗。TKI 暴露的中位时间为 3 周（范围，2-11 周）。5 次妊娠以流产告终，3 次为选择性流产。7 名男性均成功孕育了 7 名足月健康婴儿。在男性和女性（包括一对双胞胎）所生的 20 名婴儿中，有 1 名存在轻微异常。7 名女性在孕期失去反应，但在分娩结束时，除 2 名外，所有女性均恢复了 TKI 治疗并恢复了反应。9 次计划妊娠中，有 7 名女性在怀孕前停止 TKI 治疗，中位时间为 4 个月（范围，1-20 个月）；3 名女性在孕期失去反应。只有 5 名患者在分娩后恢复治疗。结果是 6 名足月健康婴儿，1 名早产婴儿，2 名流产婴儿。CML 患者在接受 TKI 治疗时怀孕可能并不复杂。虽然患者在中断治疗后可能会失去反应，但几乎所有患者在恢复治疗后都会恢复反应。孕期通常不需要治疗。
