Background

Tyrosine kinase inhibitors (TKI) treatment has transformed chronic myeloid leukemia (CML) from a fatal neoplasm to a chronic disease with normal life expectancies. Indeed, half of CML patients are able to discontinue TKI without relapse. However, it seems clearly demonstrated that exposure to TKI may result in fetal malformations. Regarding its effects on fertility, preclinical studies and clinical case reports provide inconclusive evidence. Furthermore, due to the risk of CML relapse after TKI discontinuation, the optimal time to stop TKI represents a real dilemma.

Case report

We describe a 23-year-old woman who, after more than 6 years with imatinib and 1 year in deep molecular response [(DMR), MR ≥ 4], interrupted treatment to become pregnant. After 2 failed artificial insemination cycles, she underwent one process of controlled ovarian stimulation, achieving 2 blastocyst-embryos. In the meantime, BCR-ABL1^IS levels increased despite interferon-alpha therapy, she lost the mayor molecular response (MMR), and the 2 embryos had to be cryopreserved. A stable second MR ≥ 4.0 was again obtained with nilotinib, and after stopping it, the 2 blastocyst-embryo transfers were unsuccessfully performed. Under DMR, a second ovarian stimulation and in vitro fertilization (IVF) was performed and 1 blastocyst embryo was transferred. This time, she became pregnant and a healthy baby was born. After more than 3 years of follow-up, she remains in treatment-free remission (TFR).

Conclusion

Compared with imatinib, nilotinib achieves earlier and deeper MR that allows safe and timely pregnancies in infertile CML women through IVF process, while patients remain in TFR after delivery.

中文翻译：

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一名患有慢性粒细胞白血病的不孕妇女成功进行卵巢刺激和怀孕。

背景

酪氨酸激酶抑制剂 (TKI) 治疗已将慢性粒细胞白血病 (CML) 从致命的肿瘤转变为具有正常预期寿命的慢性疾病。事实上，一半的 CML 患者能够停止 TKI 而不会复发。然而，似乎清楚地表明暴露于 TKI 可能导致胎儿畸形。关于其对生育能力的影响，临床前研究和临床病例报告提供了不确定的证据。此外，由于 TKI 停药后 CML 复发的风险，停止 TKI 的最佳时间是一个真正的困境。

案例报告

我们描述了一名 23 岁的女性，她在使用伊马替尼 6 年以上和 1 年的深度分子反应 [(DMR)，MR ≥ 4] 后中断治疗以怀孕。在 2 个失败的人工授精周期后，她接受了 1 个受控卵巢刺激过程，获得了 2 个囊胚。同时，BCR-ABL1 ^IS尽管接受了干扰素-α治疗，但她的水平仍然升高，她失去了市长分子反应 (MMR)，并且必须冷冻保存 2 个胚胎。尼罗替尼再次获得稳定的第二次MR≥4.0，停药后2次囊胚-胚胎移植均未成功。在 DMR 下，进行了第二次卵巢刺激和体外受精 (IVF)，并移植了 1 个囊胚。这一次，她怀孕了，生下了一个健康的宝宝。经过 3 年多的随访，她仍处于无治疗缓解期 (TFR)。

结论

与伊马替尼相比，尼罗替尼实现了更早、更深的MR，使不孕CML妇女通过IVF过程安全、及时地怀孕，而患者在分娩后仍保持TFR。