Pregnancy is an important topic given the increased ability to treat CML into stable and long-standing remission. Although CML is typically a disease that strikes women at the end of or beyond the childbearing years, there remains a significant minority of patients in whom CML is diagnosed and fertility remains along with the desire to have children. So what to do? Assuming pregnancy is an elective option, it is wise for a patient to defer until well into a stable remission. Thus, proper initial therapy with the aim to achieve rapid and definitive cytogenetic and molecular response according to available guidelines is first. Trials reported to date for patients in remission on tyrosine kinase inhibitor (TKI) therapy who have discontinued treatment show the prognostic value of longer duration of therapy for the likelihood of “treatment-free remission.” Consensus regarding current trials for deliberate (non-pregnancy-related) treatment cessation generally includes a 2-year period of complete molecular response (CMR; ≥4.5 log reduction below standard baseline) to maximize the odds of success off treatment. Thus, general principles of counseling for a younger woman who wishes to plan a family might include definitive TKI treatment as if participation in a treatment-free remission trial is planned, and at the point of ‘eligibility’, for instance when considered safe for consideration of treatment interruption, conception would be considered reasonable as well.

CML certainly may present in the setting of pregnancy and poses a particular challenge. The TKIs approved for use in CML are all assigned pregnancy category D status, thus advising against any use in pregnancy. Studies of pregnancy outcome with TKI exposure, with the bulk of cases in the literature describing exposure to imatinib, show a range of effects and do include the possibility of severe effects incompatible with survival of the fetus. Subsequent-generation TKIs are less well studied. Early development and TKI effects on germ cell layer and neural tube development may explain severe effects observed with very early exposure; exposure late in pregnancy (third trimester) may have much less potential for effect. Avoidance of TKI in pregnancy is thus the blanket recommendation. Rather than definitive treatment, control of CML in the setting of pregnancy may be more feasible; in particular interferon-alpha, a historic standard therapy for chronic-phase CML, now generally given in the pegylated form, can be deployed safely in pregnancy with disease control and in certain cases progress toward remission. First-trimester use of interferon may be associated with increased rates of spontaneous abortion, and timing of interferon is thus crucial. A simple goal of treatment during pregnancy might be to control blood counts to avoid placental blood flow issues and hemostatic and viscosity issues resulting from uncontrolled elevation in the leukocyte count at the time of delivery.