Treatment of Acute Leukemia During Pregnancy – 20 Years Experience

Abstract 4348

Acute leukemia during pregnancy is a rare but not an unique event: 1 case per 75–100.000 pregnant women and the majority of cases are registered in the 2^nd/3^rd trimester. The main law has to be carried out in this life threatening situation: to save two lives - mother's and child's. Though in the 1^st trimester medical abortion is highly recommended, in the 2^nd/3^rd trimester chemotherapy should be applied without dose corrections. It is considered to be of no major danger to the fetus and gives good chances to the mother.

Here we would like to report our 20 years experience with 32 pregnant women (median age 25y (19-35)) with acute leukemias: 13 AML, 5 APL and 14 ALL. 26 (81%) of them were diagnosed with AL in the 2^nd/3^rd trimester. We used the following approach: 1. up to 12 weeks of pregnancy medical abortions were performed (6 pts - 1 AML, 1- APL, 4-ALL); 2. at 35–40 weeks of pregnancy “cesar sections” were done and then chemotherapy was started (7 pts – 4 AML, 2 APL, 1 – ALL). All 7 children are alive and well; 3. at 13–34 weeks of pregnancy standard chemotherapy was applied according to AL subtype treatment protocol (19 pts – 8 AML; 2 APL, 9 ALL). In AML 7+3 protocol (ARA-C – 100 mg/m² bid 1–7 days, Daunorubicin 45 mg/m² (in 3 pts) or 60 mg/m² 1–3 days), in APL – 7+3+ATRA or AIDA (2 pts), in ALL - 8 weeks induction and prolonged post-CR therapy - were used.

All together in 13 AML pts there were 9 CR (69%), 2 ED (15,5%), 2 DR (15,5%); in 5 APL pts – 4 CR (80%), 1 ED (20%); in 14 ALL pts – 9 CR (64,3%), 3 DR (21,4%), 2 ED (14,3%). 85% of pts had infectious complications during induction, 1 ATRA-syndrome, 1 emergency “cezar section” was performed at 30th week of pregnancy due to premature placenta unlayment (PPU) with hemorrhage due to L-asparaginase. There was one late spontaneous abortion (+21 weeks), no deaths and no defects were registed among newborns “treated” in uteri (n=18), all of them were followed in micropediatriac departments, neutropenias was registed in half of them and pneumonias in 3 (17%). All children (n=25) are alive and well. The oldest is 20 years old now, the youngest – 10 months. The probability of 5-years overall survival in AML pts was 34,6%, in ALL – 26,7%. In APL only 1 pt is alive in 1^st CR due to 1 death in consolidation and two relapses.

Within the period of the study we have developed some practical recommendations: 1. Daunorubicin in 7+3 courses should be used at 60 mg/m² as there were no CR in pts receiving 45 mg/m². It's a crucial point as CR must be achieved after the 1^st course, especially in 30–32 weeks of pregnancy because delivery must be carried out in stable status. 2. Idarubicin can be used safely in resistant to daunorubicin AML pts and in AIDA protocol for APL. AIDA is less toxic than 7+3+ATRA for APL induction and well effective. 5-days mitoxantrone consolidation should be postponed to 3–4 months after delivery. 3. L-asparaginase should not be applied in ALL treatment during pregnancy (only after delivery) due to coagulation disturbances and possibility of premature placenta unlayment (PPU). 4. Delivery during AL treatment must be planned at 34–36 weeks of pregnancy. 60% of our patients had “cesar sections”. 5. Every day gynecologists care is absolutely needed (uteri hypertonus, fetus hypotrophy, PPU, etc). 6. Chemotherapy restart should be planned 3–4 weeks after delivery because immediate (within 5–7 days) continuation of cytostatic treatment caused severe combined infections complications due to postdelivery immunodeficiency and desadaptation. In case of resistant leukemia restart treatment in 2 weeks and not with high-dose protocols. 7. In newborn children all complications can be cured within 1–5 weeks in special micropediatic departments, children grew up healthy and intelligent. 8. The results in ALL pts with pregnancy seem to be worse than in general ALL population. 9. After CR in APL careful monitoring of MRD may provide better outcome and avoid aggressive consolidation courses.

The main conclusion that comes up from this data is the obvious necessity to treat a pregnant woman with acute leukemia diagnosed in the 2^nd/3^rd trimester with adequate chemotherapy, that results in saving the child's life and - in many cases – the mother's. The overall survival in pregnant women with acute leukemia is quite similar to the outcome in all patients, though we wished it to be better.