Cortes Jorge E, Abruzzese Elisabetta, Chelysheva Ekaterina, Guha Mausumee, Wallis Nicola, Apperley Jane F
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Hematology, S. Eugenio Hospital, Tor Vergata University, Rome, Italy.
Am J Hematol. 2015 Dec;90(12):1111-5. doi: 10.1002/ajh.24186. Epub 2015 Oct 12.
Prolonged survival in patients with chronic myeloid leukemia treated with BCR-ABL1-targeted tyrosine kinase inhibitors allows consideration of parenthood for patients on chronic therapy, but there are limited data about the effects of dasatinib on pregnancy. Pregnancy-related outcomes in dasatinib-treated patients or their partners reported to Bristol-Myers Squibb from clinical trials or healthcare providers through December 2013 were reviewed. Outcomes were available in 46/78 dasatinib-treated women (59%) and 33/69 partners of dasatinib-treated men (48%). Fifteen women (33%) delivered a normal infant; 18 (39%) and 8 (17%) had an elective or spontaneous abortion; and 5 (11%) had an abnormal pregnancy. There were 7 reports of fetal/infant abnormalities (encephalocele, renal tract abnormalities, and hydrops fetalis). Thirty of 33 (91%) infants fathered by dasatinib-treated men were reported normal at birth. Also, animal studies evaluated the impact of dasatinib on fertility, embryo-fetal toxicity, and development, suggesting that dasatinib may be a selective developmental toxicant. The outcomes of most pregnancies conceived by men treated with dasatinib were normal, but due to the small number of cases, further monitoring is required. Significant effects on pregnancy outcomes in women treated with dasatinib were found, supporting current recommendations that women avoid becoming pregnant during dasatinib treatment and be informed of fetal risks.
使用靶向 BCR-ABL1 的酪氨酸激酶抑制剂治疗的慢性髓性白血病患者生存期延长，使得处于慢性治疗阶段的患者可以考虑生育，但关于达沙替尼对妊娠影响的数据有限。回顾了截至 2013 年 12 月通过临床试验或医疗服务提供者向百时美施贵宝报告的接受达沙替尼治疗的患者或其伴侣的妊娠相关结局。46/78 名接受达沙替尼治疗的女性（59%）和 33/69 名接受达沙替尼治疗男性的伴侣（48%）有结局数据。15 名女性（33%）分娩出正常婴儿；18 名（39%）和 8 名（17%）进行了选择性或自然流产；5 名（11%）出现异常妊娠。有 7 例胎儿/婴儿异常报告（脑膨出、泌尿道异常和胎儿水肿）。33 名接受达沙替尼治疗男性所生育的婴儿中有 30 名（91%）出生时报告正常。此外，动物研究评估了达沙替尼对生育力、胚胎-胎儿毒性和发育的影响，表明达沙替尼可能是一种选择性发育毒物。大多数接受达沙替尼治疗男性所孕育妊娠的结局正常，但由于病例数较少，需要进一步监测。发现达沙替尼治疗的女性对妊娠结局有显著影响，支持目前的建议，即女性在达沙替尼治疗期间避免怀孕，并告知其胎儿风险。
