Bhattacharjee Urmimala, Jandial Aditya, Singh Charanpreet, Lekshmon K S, Mishra Kundan, Sandal Rajeev, Nampoothiri Ram, Naseem Shano, Suri Vanita, Jain Arihant, Lad Deepesh P, Prakash Gaurav, Khadwal Alka, Malhotra Pankaj
Department of Clinical Haematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Leuk Res. 2023 Oct;133:107367. doi: 10.1016/j.leukres.2023.107367. Epub 2023 Aug 2.
Despite the general recommendation to avoid Tyrosine Kinase Inhibitors (TKIs) for Chronic Myeloid Leukemia (CML) during pregnancy, unplanned pregnancies still occur, particularly among female patients residing in low- and middle-income countries (LMICs). We aimed to investigate the outcomes of pregnancy, foetal development, and disease progression among female CML patients in chronic phase (CML-CP) undergoing TKI therapy who encountered unplanned pregnancies in a tertiary care hospital in northern India.
We conducted a retrospective analysis of all pregnancies in female CML-CP between January 2002 and December 2022 at our hospital. Patients were included if they had a confirmed diagnosis of CML-CP, were receiving TKI therapy during conception, and had available medical records. We analysed the data on pregnancy outcomes, foetal development, and disease progression through a review of medical records.
We identified 36 pregnancies in female CML-CP patients on TKI therapy during the study period, with 33 (91.7%) being unplanned. Sixteen pregnancies (48.5%) were conceived at less than major molecular remission (MMR) status. Twelve pregnancies (36.4%) were electively terminated, 4 (12.1%) had miscarriages, and, 17 (51.5%) pregnancies resulted in childbirth. Out of the 17 childbirths, 10 were full-term deliveries, and 7 were preterm deliveries. Twin pregnancies had a high incidence (18.2%). Among the 21 pregnancies that were not electively terminated, TKI was stopped at the first pregnancy detection in 14 pregnancies, while imatinib was continued throughout 7 pregnancies. Patients who discontinued TKI had a higher but statistically non-significant incidence of adverse pregnancy outcomes compared to those who continued imatinib throughout pregnancy (64.2% vs. 28.6%, p = 0.18). Additionally, the risk of long-term disease progression among patients who discontinued TKI during pregnancy and those who continued imatinib throughout pregnancy was 21.4% and 16.7% (p = 0.9), respectively. The risk of long-term disease progression was significantly increased in those persistently at less than MMR pre- and post-gestation (p = 0.0002).
Our findings suggest that continuing imatinib therapy during pregnancy, may be a reasonable option for CML patients residing in low- and middle-income countries to reduce the risk of disease progression and adverse pregnancy outcomes. Patients persistently at less than MMR levels pre- and post-gestation should be closely monitored for the risk of long-term disease progression. Further studies with larger sample sizes are needed to confirm these results.
尽管普遍建议在孕期避免对慢性髓性白血病（CML）患者使用酪氨酸激酶抑制剂（TKIs），但意外怀孕仍时有发生，尤其是在低收入和中等收入国家（LMICs）的女性患者中。我们旨在调查印度北部一家三级护理医院中，处于慢性期（CML-CP）且正在接受TKI治疗的女性CML患者发生意外怀孕后的妊娠结局、胎儿发育及疾病进展情况。
我们对2002年1月至2022年12月期间我院女性CML-CP患者的所有妊娠情况进行了回顾性分析。纳入标准为确诊为CML-CP、受孕期间正在接受TKI治疗且有可用医疗记录的患者。我们通过查阅医疗记录分析了妊娠结局、胎儿发育及疾病进展的数据。
在研究期间，我们确定了36例接受TKI治疗的女性CML-CP患者妊娠，其中33例（91.7%）为意外怀孕。16例妊娠（48.5%）是在未达到主要分子缓解（MMR）状态时受孕的。12例妊娠（36.4%）被选择性终止，4例（12.1%）发生流产，17例（51.5%）妊娠成功分娩。在17例分娩中，10例为足月分娩，7例为早产。双胎妊娠发生率较高（18.2%）。在21例未被选择性终止的妊娠中，14例在首次检测到怀孕时停用了TKI，而7例在整个孕期继续使用伊马替尼。与整个孕期继续使用伊马替尼的患者相比，停用TKI的患者不良妊娠结局发生率更高，但差异无统计学意义（64.2%对28.6%，p = 0.18）。此外，孕期停用TKI的患者和整个孕期继续使用伊马替尼的患者长期疾病进展风险分别为21.4%和16.7%（p = 0.9）。妊娠前后持续未达到MMR状态的患者长期疾病进展风险显著增加（p = 0.0002）。
我们的研究结果表明，对于低收入和中等收入国家的CML患者，孕期继续使用伊马替尼治疗可能是降低疾病进展风险和不良妊娠结局的合理选择。妊娠前后持续未达到MMR水平的患者应密切监测长期疾病进展风险。需要进一步开展更大样本量的研究来证实这些结果。
