Evaluating the Safety of Tyrosine Kinase Inhibitors in Pregnant Patients with Chronic Myeloid Leukemia: A Comprehensive 15-Year Single-Center Analysis

Managing chronic myeloid leukemia (CML) during pregnancy is challenging because tyrosine kinase inhibitors (TKIs) have potential fetal risks, especially with first-trimester exposure. Evidence from routine practice remains limited in some regions, particularly where unplanned pregnancies are common. We conducted a retrospective analysis of prospectively collected data from the CML registry at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, spanning 2005 to 2020. The study encompassed 51 female patients with Philadelphia chromosome-positive CML who experienced 99 pregnancies during the observation period. Primary endpoints included pregnancy outcomes, maternal complications, and fetal health parameters. Secondary endpoints assessed postpartum molecular response recovery. The median age at CML diagnosis was 28 years (range, 15–41), with a median age of 32 years (range, 21–47) during pregnancy. Of 99 pregnancies, 95 (96.0%) were unplanned. Among unplanned pregnancies, 82 (86.3%) involved confirmed TKI exposure during organogenesis (gestational weeks 3–8, calculated from LMP). Imatinib was the predominant TKI (46.5%), followed by nilotinib and dasatinib (8.1% each). PEG-IFN (a non-TKI therapy) was used in 8.1% of pregnancies. Twenty pregnancies (20.2%) involved no active therapy at conception. Of the documented outcomes, 58 pregnancies (58.6%) resulted in healthy live births, while miscarriages occurred in 7.1% and therapeutic abortions in 10.1%. Pregnancy-related maternal complications included gestational diabetes mellitus (8.1%) and postpartum hemorrhage (1.0%). CML disease events during pregnancy included loss of major molecular response in 3 patients (3.0%) and loss of complete cytogenetic response in 1 patient (1.0%). No disease progression to accelerated or blast phase occurred. Notably, no major congenital malformations were observed among live births. Following postpartum TKI resumption, 53.4% achieved MR4.5 and 27.6% achieved major molecular response within 12 months. This comprehensive analysis demonstrates that favorable pregnancy outcomes are achievable in CML patients with unplanned TKI exposure. The safety profile observed in this cohort, including the absence of major congenital anomalies and disease progression, supports an individualized, risk-stratified approach to pregnancy management and underscores the imperative for enhanced preconception counseling in this population.