Management of Chronic Myeloid Leukemia During Pregnancy: Review of Evidence and Treatment Algorithm

Philadelphia chromosome-positive chronic myeloid leukemia (CML) during pregnancy is rare, with an annual incidence of 1 per 100,000 pregnancies. Managing CML in pregnancy is challenging due to concerns about the teratogenicity of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). While some pregnant patients with chronic-phase CML may be managed with close monitoring and no therapy, others, particularly those diagnosed in the first trimester, may require treatment to prevent disease progression and maternal complications. Imatinib has been associated with an increased risk of congenital malformations when used in the first trimester; however, growing evidence support its safety later in the second and third trimesters. Similar to imatinib, nilotinib has limited placental transfer with no congenital malformations reported to date in women who received it later in pregnancy. Dasatinib, however, is contraindicated due to its high association with congenital abnormalities and hydrops fetalis. Ponatinib exposure has been linked to a higher incidence of Hirschsprung's disease and should be avoided in pregnancy. Although no congenital malformations have been reported with bosutinib or asciminib, data remains limited, and their use is not recommended. Interferon-α is a safer alternative during pregnancy but is slower in achieving cytoreduction, and less effective compared to TKIs. Hydroxyurea, while not teratogenic, may increase the risk of miscarriage and low birth weight. If a male patient is receiving TKI therapy, the female partner can safely become pregnant without an increased risk for the fetus. Shared decision-making and thorough counseling on the risks and benefits of different treatment options are essential. This review examines the potential fetotoxicity of CML therapies, focusing on TKIs and alternative treatments for pregnant women.