Acute Myeloid Leukemia in Pregnancy

Introduction: The management of acute myeloid leukemia (AML) in pregnancy remains a daunting clinical challenge for oncologists, obstetricians, patients, and their families. Although the incidence of AML in pregnancy is low at 1 in 75,000 pregnancies, cancer represents the second most common cause of maternal death behind gestation-related vascular complications. Due to the small number of patients diagnosed during this time, there are only retrospective reviews and case series to guide complex management decisions.

Case Report: A 26-year-old Caucasian woman presented to our institution at 17 weeks gestation after she was found to have an absolute monocytosis, neutropenia, and anemia on routine prenatal evaluation. The bone marrow aspirate demonstrated a diagnosis of AML. The blast population compromised 14% of cellular elements, and fluorescence in situ hybridization (FISH) karyotyping was positive for inversion 16. She and her husband were extensively counseled regarding the diagnosis and wished to proceed with the pregnancy. She received standard dose induction chemotherapy with daunorubicin and cytarabine and achieved a complete remission. Starting at 22 weeks gestation, we proceeded with consolidation chemotherapy using intermediate-dose cytarabine 1.5 grams/m² every 12 hours on days 1, 3, and 5 of the 6 day cycle. Fetal status was monitored with serial growth ultrasounds and daily tocographic assessment. She tolerated the first cycle well and starting at 28 weeks gestation she began the second cycle of consolidation. She was induced at 35 weeks gestation and delivered a morphologically normal male in good health weighing 5 pounds and 9 ounces. She received her final two cycles of consolidation post-partum, and cytarabine dose was increased to 3 grams/m² for the standard high-dose regimen. Throughout pregnancy, her care was managed by a multidisciplinary team which included neonatology, maternal fetal medicine, and oncology. Expert opinion was solicited from top medical centers across the country for guidance on consolidation therapy.

Discussion: Our case highlights the complexities of AML management in pregnancy. There are no formal management guidelines and sparse data on consolidation during this period. The appropriate dosing of chemotherapy, fetal monitoring, and timing of delivery all represent challenges in providing optimal care and improving maternal and fetal overall survival. In a recent meta-analysis, the maternal median overall survival rate for 87 women with AML in pregnancy was found to be 30%. The live birth rate in this study for chemotherapy-exposed neonates was 87%, and the complication rate was 16%. These complications included unspecified deformations, patent ductus arteriosus, hydrocephalus, ventricular septal defect, cytopenias, intracranial hemorrhage, and respiratory compromise. Management recommendations from experts in the field showed significant heterogeneity underscoring the need for consensus guidelines.

Conclusion: There is a critical need of management guidelines to address timing and dosing of anthracycline/cytarabine based regimens, potential drug toxicity to the mother and fetus, and transplant considerations in intermediate and high-risk patients. A national registry for leukemia patients treated in pregnancy could be formed to help answer these questions and improve maternal and fetal overall survival rates. Delays in chemotherapy should be avoided, and a multidisciplinary team is needed to provide comprehensive care to patients and their families.

Follow Up: The end of treatment bone marrow examination was negative for leukemia by morphology, cytogenetics, and FISH. The patient and child are in good health now more than two years after completion of chemotherapy.