The spectrum of leukemia in humans can range from acute to chronic leukemia. Although acute leukemia is a hematological emergency and needs treatment urgently, chronic myeloid leukemia is a lifelong illness with relatively safe targeted therapies requiring indefinite treatment. Hematopoietic stem cell transplantation (HSCT) is an important component of treatment for acute leukemia and the only chance for long-term cure for a certain subset of patients and certainly for all relapsed patients. Leukemia in pregnancy is challenging in terms of the need for urgent therapy while trying to preserve fetal viability and the complexities of the change in pharmacokinetics and pharmacodynamics of chemotherapy in the pregnant state. Although fertility preservation is frequently not feasible due to urgency of disease state, there is potential for planned fertility preservation techniques after attaining a cure. In this chapter, we discuss the unique challenges and consequences of treatment of leukemia and effect on fertility and various fertility preservation options before and after HSCT.
ACUTE MYELOID LEUKEMIA IN PREGNANCY
Acute myeloid leukemia (AML) is a relatively uncommon malignancy with an estimated incidence of 13 per 100,000 men and women per year according to CDC data.1 The median age at diagnosis is 68 years; therefore, the incidence in pregnancy is rare with an approximate incidence of 1 in 100,000 pregnancies.2,3 However, the challenges in managing AML are significant as the disease is always aggressive by nature and delaying treatment is not an option.4 The effects on the embryo and fetus are also challenging and one has to take into account the long-term developmental effects on children after exposure to AML-directed therapy for the mother during pregnancy.
The teratogenicity of chemotherapeutic agents is usually confined to the first trimester of pregnancy. The first 2 weeks of development are usually associated with cell division and embryo expansion. Exposure to chemotherapy in this period usually leads to spontaneous abortion or no damage at all.5,6 Organogenesis occurs between 3 and 8 weeks with the most teratogenicity seen in this period. Between the weeks 8 and 38, there is growth of gastrointestinal, neural, and hematopoietic tissues. Exposure to chemotherapy in the second and third trimesters usually has potential for intrauterine growth retardation and preterm labor.5,6,7,8 Cytotoxic chemotherapy with DNA-active drugs, like cyclophosphamide and anthracyclines, has been associated with small placental size.9
Chemotherapeutic Agents Used in AML
In addition to the short- and long-term effects of chemotherapeutic agents for the fetus and mother, pregnancy poses challenges in the pharmacokinetics of these drugs. Pregnancy is associated with plasma volume expansion, increased renal and hepatic clearance of drugs, and amniotic fluid third spacing. Most chemotherapeutic agents used in the treatment of AML are of low molecular weight and can easily cross the placental barrier.5,6