Hôpital universitaire Necker - Enfants malades, Pharmacie, F-75015, Paris, France.
Hôpital universitaire Necker - Enfants malades, Hématologie adultes, F-75015, Paris, France.
BMC Pregnancy Childbirth. 2020 Apr 19;20(1):231. doi: 10.1186/s12884-020-02928-6.
Hodgkin lymphoma (HL) is the most common hematological malignancy during pregnancy. The first-line treatment for HL in pregnancy is the standard ABVD regimen without any drug and/or dose adjustment. However, data on chemotherapy during twin pregnancies are sparse, and a better understanding of the mechanisms involved in exposure to and the toxic effects of anticancer drugs in the fetuses is needed.
A 41-year-old dichorionic diamniotic pregnant patient was given ABVD treatment for HL at a gestational age of 28 weeks and 3 days. The patient received 2 cycles of chemotherapy with a 15-day therapeutic window including an actual 25 mg/m dose of doxorubicin per cycle. Unlike the female twin, the male twin presented four days after birth a left cardiac dysfunction. Doxorubicin cardiotoxicity in the male newborn was also supported by high blood levels of troponin. At one month of age, echocardiography findings were normal. We investigated literature data on physiological aspects of pregnancy that may influence doxorubicin pharmacokinetics, and pharmacodynamic and pharmacokinetic data on the use of doxorubicin in pregnancy. We detailed the role of the transporters in doxorubicin placenta distribution, and tried to understand why only one fetus was affected.
Fetal safety depends at least on maternal doxorubicin pharmacokinetics.Because of drug interactions (i.e. drug metabolism and drug transport), care should always be taken to avoid maternal pharmacokinetic variability. The toxic effects were discrepant between the dizygotic twins, suggesting additional fetus-specific pharmacokinetic/pharmacodynamic factors in doxorubicin toxicity.
霍奇金淋巴瘤（HL）是妊娠期间最常见的血液系统恶性肿瘤。HL 妊娠患者的一线治疗是标准 ABVD 方案，无需进行任何药物和/或剂量调整。然而，关于双胎妊娠时化疗的数据较少，需要更好地了解胎儿接触和抗癌药物毒性作用的相关机制。
一名 41 岁的双绒毛膜双羊膜妊娠患者在妊娠 28 周 3 天时接受 ABVD 治疗 HL。患者接受了 2 个周期的化疗，治疗窗口为 15 天，每个周期实际使用 25mg/m 的多柔比星剂量。与女性胎儿不同，男性胎儿在出生后第 4 天出现左心功能障碍。男性新生儿的多柔比星心脏毒性也得到了肌钙蛋白血水平升高的支持。在 1 个月大时，超声心动图检查结果正常。我们调查了与妊娠期间可能影响多柔比星药代动力学、妊娠期间多柔比星使用的药效学和药代动力学相关的文献数据。我们详细研究了多柔比星在胎盘分布中转运体的作用，并试图了解为什么只有一个胎儿受到影响。
胎儿的安全性至少取决于母体多柔比星的药代动力学。由于药物相互作用（即药物代谢和药物转运），始终应注意避免母体药代动力学的变异性。这对双胎妊娠中的 dizygotic 双胞胎来说是一个巨大的挑战。由于药物相互作用（如药物代谢和药物转运），始终应注意避免母体药代动力学的变异性。多柔比星毒性作用在双胎妊娠中的 dizygotic 双胞胎之间存在差异，提示在多柔比星毒性中存在额外的胎儿特异性药代动力学/药效学因素。
