Outcomes of Acute Promyelocytic Leukemia (APL) during Pregnancy: A Systematic Review of Outcomes

Background: Acute promyelocytic leukemia (APL) accounts for 10-15% of all acute myeloid leukemia (AML) cases. It typically presents at a relatively early age when compared to other AML types, around the 40s.The treatment of APL) during pregnancy presents significant challenges, particularly during the first trimester due to the teratogenic effect of all-trans retinoic acid (ATRA). Standard therapy involves a combination of ATRA and arsenic trioxide (ATO), which have shown high efficacy in non-high-risk APL patients. High-risk patients typically receive induction treatment with ATRA and idarubicin (AIDA), followed by consolidation with ATRA and idarubicin/cytarabine or mitoxantrone. This systematic review aims to update the literature on the management outcomes of APL during pregnancy.

Methods: We conducted a comprehensive literature search of the PubMed database, focusing on titles and abstracts. We included case reports, case series, and retrospective cohort studies, while excluding the review articles. We identified 113 patients from 76 studies. We extracted and analyzed data on patient demographics, treatment regimens, and outcomes.

Results: The median age of the patients was 28 years (range 16-41), with a mean gestational age of 25 weeks (range 3-42). 17 patients were in the first trimester, 54 in the second trimester, and 41 in the third trimester, with one case where the trimester was not specified. Regarding induction therapy, 34 patients received ATRA only, with 27 achieving complete remission (CR) (79.41%, CI 95% : 65.83-92.99); 43 received ATRA plus chemotherapy, with 40 achieving CR (93.02%, CI 95% : 85.42-100); 20 received chemotherapy alone, with 16 achieving CR (80%, CI 95% : 62.48-97.52); and 12 received ATO with or without ATRA and/or chemotherapy, with 11 achieving CR (91.67%, CI 95% : 76.01-100). Among the 113 patients, there were 34 abortions: 15 in the first trimester, 16 in the second trimester, 2 in the third trimester, and 1 with an unspecified timing. Seventy-nine patients had deliveries, comprising 45 cesarean sections, 32 vaginal deliveries, and 2 with unspecified methods. Among patients who achieved CR, unintentional abortions occurred in 2 of 16 patients treated with chemotherapy alone, 2 of 27 treated with ATRA alone, 6 of 40 treated with ATRA plus chemotherapy, and 1 of 11 treated with ATO with or without ATRA and/or chemotherapy.

Conclusion: Managing APL during pregnancy, particularly with the advent of ATO, has shown promising outcomes, though first-trimester treatment remains complex due to teratogenic risks. Our systematic review provides updated insight into the efficacy and safety of various treatment regimens, underscoring the necessity for careful monitoring and individualized therapeutic approaches to optimize outcomes for both the mother and fetus. Further research is needed to establish standardized guidelines and improve the management of APL in pregnant patients, ensuring both maternal and fetal safety.