Two decades of pregnancy outcomes in women with CML: Insights from a real-world single-center cohort

Abstract Background: The advent of tyrosine kinase inhibitors (TKIs) has transformed Chronic Myeloid Leukemia (CML) from a fatal disease into a chronic condition with near-normal life expectancy. This has led to increasing numbers of young women with CML considering pregnancy. However, managing pregnancy in these patients remains challenging due to concerns about timing of conception, TKI exposure, and fetal outcomes. Aim: To evaluate maternal and fetal outcomes of pregnancies in women with CML over a 20-year period at a single tertiary cancer center. Methods: This retrospective observational study analyzed pregnancies in women with CML treated at our center between 2004 and 2024. Data on patient demographics, disease status at conception, TKI exposure, pregnancy outcomes, fetal complications, and post-pregnancy disease course were collected and analyzed. Results: Ninety-seven pregnancies in 62 women with CML were included. Six patients were diagnosed during pregnancy. Seventeen women conceived twice, five conceived thrice, one conceived four times, and one conceived six times. The median age at CML diagnosis was 22 years (range: 7–32), and median age at conception was 27 years (range: 19–38). At diagnosis, 56 patients were in chronic phase, three in accelerated phase, and three in blast crisis. Of 82 pregnancies with known TKI exposure, 76 occurred on imatinib, five on dasatinib, and one on nilotinib. Nine pregnancies were planned with TKI discontinuation, seven occurred during treatment-free remission (TFR), and two occurred without regular follow-up. Median TKI exposure duration before stopping post-confirmation of pregnancy was six weeks (range: 0–38). Nine patients continued imatinib throughout pregnancy, resulting in three live births, two intrauterine deaths (IUD), and three preterm deliveries. Two neonates died within a day; one had congenital anomalies (imperforate anus and septal defects). Among 76 pregnancies with known imatinib doses, 67 were on 400 mg, seven on 600 mg, and two on 800 mg. Higher imatinib doses correlated with adverse outcomes: the 800 mg group had one IUD and one neonatal death; the 600 mg group had two IUDs and two medical terminations due to severe IUGR. Six pregnancies occurred while on second-generation TKIs: five on dasatinib and one on nilotinib. Among dasatinib-exposed patients, one had two conceptions: the first electively terminated and the second resulting in a healthy baby after early drug discontinuation. One patient continued dasatinib for five months and terminated due to fetal anomalies; her subsequent pregnancy, after early discontinuation, is ongoing. Another conceived via IVF post-dasatinib and delivered a healthy child. The nilotinib-exposed patient delivered a healthy neonate. Six CML cases diagnosed during pregnancy: 2 MTPs, 2 live births with low birth weight (no TKI), 1 intrauterine growth-restricted neonatal death (Imatinib from 5th month), 1 normal baby on imatinib (last trimester only). Overall, outcomes included 55 live births (56.7%), 19 medical terminations (19.6%), eight spontaneous abortions (8.2%), three preterm deliveries (3.1%), two IUDs, three ongoing pregnancies, and one lost to follow-up. Medical terminations were mainly due to fetal outcome concerns, IUGR, social reasons, or first-trimester drug exposures. Only one case of congenital anomaly was reported in a neonate exposed to imatinib throughout pregnancy; all other live births had normal developmental milestones. Most patients regained major molecular response (MMR) within six months of restarting therapy postpartum. Complications included one case of progression to blast crisis with IUD, one T315I mutation with subsequent death, and two secondary malignancies—one periampullary carcinoma (fatal) and one teratoma (currently in TFR). Four patients are in sustained TFR. Conclusion: With careful planning, pregnancy in CML is feasible and safe. Optimal outcomes are seen when conception occurs in complete hematologic or molecular response, or during TFR. Early TKI discontinuation, close monitoring, and individualized risk-benefit assessment are critical. Prolonged TKI exposure, particularly at higher doses or in advanced phases, is associated with adverse fetal outcomes. Reintroduction of imatinib in the later trimesters due to loss of MMR appears to be safe and does not negatively impact fetal health. These real-world findings support a multidisciplinary approach to fertility and pregnancy management in CML.