Zhao H F, Zhang Yanli, Li Z, Zhou J, Zu Y L, Yu F K, Gui R R, Wei X D, Song Y P
Department of Hematology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.
Zhonghua Xue Ye Xue Za Zhi. 2018 Jul 14;39(7):540-545. doi: 10.3760/cma.j.issn.0253-2727.2018.07.003.
To explore the pregnancy outcome and disease status among patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI) when they stopped TKI treatment during pregnancy. The clinical characteristics, reproductive outcomes and disease status of the patients who stopped TKI due to pregnancy between November 2004 to November 2017 were retrospectively collected. A total of 14 CML patients in chronic phase (CML-CP), 12 patients were Sokal-low-risk. The median time of TKI treatment was 46.5 (15-123) months before the drug was stopped. The median age at the time of pregnancy was 29 (24-32) years. The median time of TKI exposure was 4 (0-9) weeks in 12 accidental pregnancies. Outcomes were available for 13 pregnancies, 9 cases (69.2%) delivered healthy babies, 1 case (7.7%) delivered polydactylia malformation baby, 3 cases (23.1%) had spontaneous abortion. The last one was still in pregnancy (no organ malformations were observed in color Doppler ultrasound). At the end of the follow up date, 10 children developed normal, the median age was 14 (0.7-65) months. Of the 14 patients who stopped TKI, 7 in complete molecular response (CMR), 3 in MR(4) (BCR-ABL(IS) <0.01%, ABL transcript >10 000), 2 in major molecular response (MMR), 2 in complete cytogenetic response (CCyR). The median time of TKI discontinuation during pregnancy was 33.5 (4-40) weeks. At the end of pregnancy, 4 cases were in CMR, 4 in MR(4), 1 in MMR and 4 in CCyR. No patients lost CCyR and complete hematologic remission. During the treatment of imatinib and Nilotinib, unplanned pregnancy may have a normal infant, but may lead to spontaneous abortion and congenital malformations. Female of CML-CP who had sustained and stable MMR at least 24 months and Sokal-low-risk had higher safety factor discontinued TKI during pregnancy, but still had a risk of increasing tumor load, so monitored the level of BCR-ABL of peripheral blood monthly during pregnancy is necessary.
探讨慢性髓性白血病（CML）患者在孕期停用酪氨酸激酶抑制剂（TKI）治疗后的妊娠结局及疾病状态。回顾性收集2004年11月至2017年11月期间因妊娠而停用TKI的患者的临床特征、生殖结局及疾病状态。共有14例慢性期CML患者（CML-CP），其中12例为Sokal低危患者。停药前TKI治疗的中位时间为46.5（15 - 123）个月。妊娠时的中位年龄为29（24 - 32）岁。12例意外妊娠中TKI暴露的中位时间为4（0 - 9）周。13例妊娠有结局，9例（69.2%）分娩健康婴儿，1例（7.7%）分娩多指畸形婴儿，3例（23.1%）自然流产。最后1例仍在妊娠中（彩色多普勒超声未观察到器官畸形）。随访期末，10名儿童发育正常，中位年龄为14（0.7 - 65）个月。在14例停用TKI的患者中，7例处于完全分子反应（CMR），3例处于MR(4)（BCR-ABL(IS) <0.01%，ABL转录本>10 000），2例处于主要分子反应（MMR），2例处于完全细胞遗传学反应（CCyR）。孕期停用TKI的中位时间为33.5（4 - 40）周。妊娠末期，4例处于CMR，4例处于MR(4)，1例处于MMR，4例处于CCyR。无患者失去CCyR及完全血液学缓解。在伊马替尼和尼洛替尼治疗期间，意外妊娠可能分娩正常婴儿，但可能导致自然流产和先天性畸形。至少24个月维持稳定MMR且为Sokal低危的CML-CP女性在孕期停用TKI有较高的安全系数，但仍有肿瘤负荷增加的风险，因此孕期每月监测外周血BCR-ABL水平是必要的。
