What is the recommended chemotherapy approach for acute myeloid leukemia (AML) in pregnant women?

AML Chemotherapy in Pregnancy

Treatment should begin immediately without delay regardless of trimester, as any delay compromises maternal survival; however, the specific chemotherapy regimen must be modified based on gestational age to balance maternal cure with fetal safety. 1

Immediate Management Principles

Multidisciplinary team involvement is mandatory, including hematologist, obstetrician, and neonatologist from the moment of diagnosis. 1, 2

Treatment delays to "wait for a safer time" are unacceptable—pregnancy does not alter AML's aggressive course, and more than 75% of pregnant patients achieve complete remission with appropriate chemotherapy. 1

First Trimester (Weeks 2-13)

Critical Decision Point

The option of therapeutic termination must be discussed with the patient once hemodynamically stable, as this allows immediate initiation of standard ATRA-containing regimens for APL or full-dose anthracycline-cytarabine for other AML subtypes. 1

If Pregnancy Continuation Desired

Use daunorubicin monotherapy (NOT idarubicin) if the patient declines termination. 1

• Idarubicin is contraindicated due to higher lipophilicity causing increased placental transfer and greater fetal toxicity 1
• Daunorubicin has more published safety experience in pregnancy 1
• Cytarabine can be added, though malformations after first-trimester exposure to anthracyclines and cytarabine have been reported 1
• ATRA is absolutely contraindicated in first trimester due to high teratogenicity (related to isotretinoin) 1
• Arsenic trioxide is contraindicated at ANY stage of pregnancy due to severe embryotoxicity 1

Important Caveat

Chemotherapy alone (without ATRA in APL cases) carries increased hemorrhagic risk from procoagulant release by promyelocytes. 1

Second and Third Trimesters (Week 14 onward)

Standard Chemotherapy Approach

Use standard daunorubicin 60 mg/m² days 1-3 plus cytarabine 100-200 mg/m² days 1-7 (3+7 regimen) dosed by actual body weight. 3, 2, 4

• This anthracycline-cytarabine based regimen achieves 87-91% complete remission rates 3, 4
• Live birth rate is 87% with this approach 4
• Chemotherapy appears reasonably safe during second/third trimester, though risks include premature delivery, low birth weight, and intrauterine growth restriction 1

For APL Specifically

ATRA can be safely added to chemotherapy starting in the second trimester. 1

Arsenic derivatives remain absolutely contraindicated throughout all trimesters. 1

Timing of Delivery Considerations

Gestational Age-Based Algorithm

Beyond 32 weeks: Consider delivering the fetus prior to starting chemotherapy 2

Between 24-32 weeks: Balance chemotherapy exposure risks against prematurity risks—generally favor chemotherapy administration with planned delivery timing 2

Before 24 weeks: Proceed with chemotherapy; pregnancy continuation is feasible 2

Delivery Planning

Plan delivery for at least 3 weeks post-chemotherapy to minimize neonatal myelosuppression risk. 2

• Administer corticosteroids if delivery anticipated between 24-35 weeks to reduce respiratory distress syndrome 5, 2
• Avoid delivery during maternal or fetal cytopenias 1
• Induction of labor preferred over spontaneous labor for better management 2
• Cesarean section only for obstetric indications, not routinely 2

Supportive Care Modifications

Antimicrobials in Pregnancy

Avoid quinolones, tetracyclines, and sulfonamides. 2

Use amphotericin B or lipid formulations as antifungal of choice. 2

Transfusion Support

Use CMV-negative blood products regardless of maternal CMV serostatus. 2

Avoid epidural analgesia if platelets <80 × 10⁹/L or WBC <1 × 10⁹/L. 2

Neonatal Outcomes and Monitoring

Fetal complications occur in 16% of chemotherapy-exposed neonates, including transient leukopenia and need for temporary oxygen therapy. 3

Daily fetal monitoring should be performed during chemotherapy administration. 3

Long-term follow-up data show normal growth and development in exposed children. 3, 6

Critical Pitfalls to Avoid

• Never use idarubicin—always choose daunorubicin 1
• Never delay treatment to reach a "safer" gestational age—maternal mortality increases with delays 1
• Never use arsenic trioxide at any trimester 1
• Never dose-reduce chemotherapy—use actual body weight dosing 2
• Never assume first-trimester chemotherapy is safe—teratogenicity risk is 10-20% during organogenesis 1, 7