Introduction Management of acute leukemia (AL) during pregnancy remains challenging. In the first trimester, chemotherapy is toxic to the fetus, while delaying treatment may endanger maternal health, often prompting recommendations for pregnancy termination. In later trimesters, although the risk of congenital malformations decreases, complications such as preterm labor remain prevalent. Delivery prior to chemotherapy may be considered in advanced gestation. This study aimed to describe maternal and fetal outcomes of patients diagnosed with AL during pregnancy.

Methods Following institutional review board approval, we retrospectively identified pregnant patients diagnosed with AL between 1995 and 2025 across Mayo Clinic sites (Minnesota, Arizona, Florida). We recorded leukemia subtype, treatment course, maternal and fetal outcomes.

Results We identified 18 patients diagnosed with AL during pregnancy, including 11 with acute myeloid leukemia (AML) and 7 with acute lymphoblastic leukemia (ALL). Ten were diagnosed in the first trimester, 3 in the second, and 5 in the third.

In the AML group (n=11; median age 30 years, range 18-42), one patient had acute promyelocytic leukemia (APL). ELN 2022 risk stratification was favorable in 5 (45%), intermediate in 4 (36%), and adverse in 2 (18%). In the ALL group (n=7; median age 23 years, range 19-34), 5 had B-ALL (one Philadelphia chromosome-positive) and 2 had T-ALL. All ALL cases were diagnosed in the first trimester. Among first-trimester AMLs, 2 of 3 had core-binding factor (CBF) AML. All eight patients diagnosed in the second and third trimesters had AML (1 APL, 2 CBF AML, 1 KMT2A-rearranged, 1 with DEK::NUP214 fusion, 1 complex karyotype including t(8;21), 2 with normal karyotype).

Overall, 15 (83%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) after initial induction. One patient had refractory disease and achieved partial remission after salvage, another had refractory disease and achieved CR after multiple lines of therapy, and a third achieved CR after FLAG-idarubicin and revumenib. Five patients received chemotherapy during pregnancy (3 in the first trimester, 1 in the second, 1 in the third); two of these resulted in live births.

Among the 10 patients diagnosed in the first trimester, all underwent therapeutic or spontaneous abortion. Of the 3 second-trimester diagnoses, 2 underwent spontaneous or therapeutic abortion at 15 weeks. The third received 7+3 induction at 24 weeks for KMT2A-rearranged AML, followed by preterm delivery at 26 weeks and re-induction with FLAG-idarubicin plus revumenib, achieving CR. Among the 5 third trimester diagnoses, 4 delivered preterm infants (median gestational age 33 weeks) prior to chemotherapy. One patient received 7+3 at 29 weeks and delivered a viable preterm infant at 36 weeks.

At a median follow-up of 6.5 years, 5 of 11 patients with AML (45%) and 3 of 7 patients with ALL (43%) died, mostly due to disease progression. Median overall survival was not reached in either group. Causes of death were as follows: 1 of AML, 1 of ALL, 3 of acute stem cell transplant (SCT) complications, 1 of chronic SCT complications, 1 of Hodgkin lymphoma, and 1 of pneumonia.

Among patients diagnosed in the second and third trimesters (n=8, all with AML), 6 (75%) resulted in live births: 5 of 5 (100%) third-trimester diagnoses and 1 of 3 (33%) second-trimester diagnoses. All received intensive induction: 7+3 (n=5), 7+3 + ATRA (n=1), 7+3 + gilteritinib (n=1), and 7+3 + nilotinib (n=1). Of the second-trimester group, only one received induction prior to delivery; she later achieved CR with FLAG-ida and revumenib. Among the third-trimester group, one patient received chemotherapy prior to delivery and achieved CR followed by SCT. All but one of the 8 AML patients achieved CR after initial therapy.

Conclusions Successful pregnancy outcomes were achieved in 75% of patients diagnosed with AML during the late second or third trimester. Notably, 5 (28%) of patients received chemotherapy during pregnancy. Larger, multi-institutional cohorts are warranted to further characterize the incidence and outcomes of AL in pregnancy.

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2025
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