Acute Leukaemia in Pregnancy: A Systematic Review of Maternal and Fetal Outcomes

Background: The management of pregnancy-associated acute leukemia (PA-AL) is challenging because of its high mortality and complication rates. Treatment decisions are complex, depending on gestation at diagnosis, therapeutic options, and maternal and fetal risks. Due to the rarity of PA-AL, current management guidelines are mainly based on expert recommendations and case reports.

Methods: A systematic search of the PubMed scholar database (from January 1, 2000, to March 31, 2024) was performed. The search was restricted to English and peer-reviewed publications, and the reference lists of the systematic reviews from the results were scanned for additional relevant publications. Studies that described women who were diagnosed with acute leukemia during pregnancy or 12 months postpartum and reported treatment regimens and maternal and fetal outcomes were retrieved for review. Studies that described haematological malignancies in pregnancy, excluding acute leukemia, and studies published before 2000 were excluded.

Results: Sixty articles (311 cases) met the inclusion criteria. The median age was 29 years (range, 16-45) years; 21.9% were diagnosed in the first trimester, 42.8% in the second trimester, 33.6% in the third trimester, and 1.7% postpartum. There were 245 cases of acute myeloid leukemia (AML), including 92 cases of acute promyelocytic leukemia (APL), 64 cases of acute lymphoblastic leukemia (ALL) and 2 cases of mixed-phenotype acute leukemia. Our study found significant variability in the treatment regimens, especially for ALL. The overall progression-free survival (PFS) was 57.3%. The PFS with delayed treatment until postpartum (43.8%) was lower than that of those who received treatment during pregnancy (72.1%, p < 0.001), with differences found in the complete remission rate between those who delayed treatment until postpartum (67.5%) and those who received treatment during pregnancy (73.5%). PFS was higher in the APL subgroup (73.9%) than in the AML and ALL subgroups (46.3% vs. 37.5%; p = 0.016). Overall, 166 live births (56.1%) were reported, of which 51.8% were preterm births. The neonatal complication rate in live births was 13.9%, with 91.3% of events occurring in neonates with in utero exposure to chemotherapy. Neonatal complications included congenital malformations (encephalomalacia, limb deformities), pulmonary (neonatal respiratory distress syndrome, pulmonary hypoplasia, hypoxic respiratory failure, apnea, and cyanosis), cardiovascular (transient dilated cardiomyopathy), haematological (anemia), fetal growth restriction, and others (jaundice, necrotizing enterocolitis).

Conclusion: This study demonstrated encouraging maternal and neonatal outcomes with in utero chemotherapy exposure beyond the first trimester. Maternal survival outcomes were worse when treatment was delayed until the postpartum period. There were significant variations in the chemotherapy regimens, indicating diversity in clinical practice and advances in therapy over time. This study provides a foundation for future treatment strategies for PA-AL, given the limited data available on novel therapeutics in pregnancy.