Pregnancy Is a Poor Prognostic Factor for AML Outcome
Authors: Troitskaya Vera V. , Parovichnikova Elena N. , Sokolov Andrey N. , Kokhno Alina , Fidarova Zalina T. , Sidorova Anna A. , Gavrilina Olga A. , Galstian Gennadii M. , Bazhenov Aleksei , Kuzmina Larisa A. , Drokov Mikhail Yu. , Makhinya Sergei , Latishkevich Oleg , Zvereva Alexandra , Savchenko Valery G 
Published: October 2019

Abstract
Acute myelogenous leukemia (AML) and pregnancy - a rare combination, which limits the possibility of large prospective studies. All publications present small retrospective studies and case reports, and most of them conclude that diagnosis of acute leukemia during pregnancy does not affect the prognosis.
Aim - to assess the pregnancy as independent prognostic factor in female AML patients (pts) in reproductive age.
From 1990 to 2016 the Russian Acute Leukemia study group has treated 27 de novo and 2 relapsed pregnant women with AML (Me - 34 (22-40) yrs) - 1st group. APL-pts were not enrolled in this study. Among pts (23/29), whom available cytogenetic data 43,5% pts were attributed to the poor prognostic cytogenetic group. AML was diagnosed in the IInd trimester of pregnancy in 13 women, in the IIIrd - in 16. Chemotherapy (CT) regime 7+3 was applied in the majority of pts: either with daunorubicin 45-60 mg/m2, or mitoxantrone (10 mg/m2), or idarubicin (12 mg/m2). 2 refractory/relapsed AML-pts were treated by low doses ARA-C (20 mg/m2/day, 28 days).
11 women delivered at 34-40 weeks of gestation age before CT was started. 4/11 pts had vaginal birth and 7 - delivery by caesarean section. One pt died in the early postpartum period due to leukemia progression. CT was started in 10 pts at 7 (1-60) days after delivery.
18 women received CT during pregnancy. CT was started at 23 (14-32nd) weeks of gestation. 7 pts received 1 cycle, 9 - 2 cycles, 2 - 3 cycles of CT before delivery. 2/18 (11%) pts died during induction due to severe infections in aplasia. Antenatal fetal mortality was registered in one pt at the 32nd week of gestation. Delivery was planned at 34 (31-37) weeks of gestation and only 8/15 pts were in complete remission (CR) at the time of delivery. 2 CR-pts delivered by their own and 13 - by caesarean section. 7/15 pts (46,4%) were required urgent caesarean section due to infectious complications, or/and fetal developmental delays, and refractory AML. The time between CT and delivery was 23 days (2-30 days) and from delivery to the restart of CT - 14 days (3-30). 26 children were born (boys - 20 girls - 6). 24/26 are alive and healthy with a follow-up from 3 months to 25 yrs (Me - 97 months), 2 - died at the age of 1 month (Down's syndrome with complex congenital heart disease; prematurity (31 weeks of gestation age) and pneumonia).
In overall, 1 woman died before CT. Second remission in was not achieved 2 relapsed-pts and they dead after delivery due to refractory AML. Induction mortality occurred in 7,4% (n=2). CR was achieved in 20/27 de novo AML-pts (74%): after 1st course CT - in 12/27 and after 2nd - 8/27 pts. Primary resistance was registered in 6/27 pts (22,2%). Among pts, whom available cytogenetic data, CR was archived in 75% (9/12) from int. and in 60% (6/10) from the poor prognostic group. 15/20 CR-pts had relapsed (75%). After childbirth allogenic bone marrow transplantation (allo-BMT) was performed in 9 of 24 (37,5%) de novo AML-pts who survived induction-therapy. 3 pts relapsed after allo-BMT and 1 woman remained with refractory AML after allo-BMT. Only 8 of 27 (29,6%) de novo AML-pts are alive now (in CR-7, without CR-1) at 18 (7-222) months, 6 of them are alive after allo-BMT.
Our results demonstrate quite low OS (A) and DFS (B) (11,7% and 22,9% respectively) for female AML-pts diagnosed during pregnancy (Fig. 1). Prolonged OS and DFS were achieved only in pts after allo-BMT. Due to long period of observation and different in supportive care in last 25 years, we conducted a comparative analysis 13 pregnant women and 26 AML female pts in reproductive age (<51 yrs) (Me - 38 (20-51) yrs), not pregnant at time of diagnosis treated in 2010-2016. Pregnancy was a poor prognostic factor for 3-yrs OS (C) and DFS (D) in AML female pts in reproductive age (Fig. 1).
The multivariate Cox model, with clinical variables such as age, pregnancy and allo-BMT included as potential risk factors, revealed that pregnancy hazard ratio (HR)(95%CI) for OS and DFS was 4.088 ((1.153-14.493); p=0.029) and 6.979 ((1.708-28.514); p=0.007) respectively. Cox model revealed that pregnancy were significantly correlated with OS and DFS in female AML-pts in reproductive age and all these pts have to consider as candidates for allo-BMT in 1st CR.
Figure 1 Overall (A) and disease-free (B) survival for AML patients with pregnancy. 3-yrs OS (C) and DFS (D) of AML-pts with (green) and without pregnancy (blue). Figure 1. Overall (A) and disease-free (B) survival for AML patients with pregnancy. 3-yrs OS (C) and DFS (D) of AML-pts with (green) and without pregnancy (blue).

Disclosures
No relevant conflicts of interest to declare.