Successful Pregnancy In APL Patients Treated According to the AIDA Protocol.
Authors: Carluccio Paola , Ricco Alessandra , Pastore Domenico , Breccia Massimo , Kropp Maria Grazia , Bona Eros Di , Fabbiano Francesco , Ferrara Felicetto , Melillo Lorella , Lo-Coco Francesco , Specchia Giorgina 
Published: October 2019

Abstract
Abstract 1037

Background
Among all the AML subtypes, APL has the distinction of being the most curable. The median age at diagnosis is 40 years, which is younger than with other AML subtypes. The fact that APL is more common in younger patients increases the likelihood that it may occur during fertile age. The introduction of ATRA and ATO has substantially modified the outcome of APL: in two successive studies 94% of patients achieved CR and the 6-yr OS rates (PETHEMA and GIMEMA) were about 80%.
ATRA is highly effective in APL patients, but adverse effects such as retinoic acid syndrome, arrhythmias, headache, rash, dizziness have been reported. Moreover, retinoids are known to be teratogens and increased rates of spontaneous abortion and major fetal abnormalities have been reported. Most of the cases reported suggest that ATRA is relatively safe for both mother and fetus when used in the second and third trimesters. By contrast, when it was used in the first trimester, a negative foetal outcome was reported. No data have yet been reported on the outcomes of pregnancies in young patients with APL, occurring during CCR following ATRA-including chemotherapy regimens.

Methods
Herein we report 20 female patients who successfully conceived 21 healthy fetuses (two twins) and the outcomes in the patients and newborns. Clinical and demographic features of the 20 patients were as follows: median age at onset 25 yr. (range 18–35); according to the FAB classification 18 were M3 and 2 M3v, 8 at low, 10 intermediate and 2 high risk, with 13 bcr1, 1 bcr2 and 6 bcr3 PML/RARA fusion gene type. All the patients were treated according to the AIDA protocol, all achieved CR after induction and Complete Molecular Remission (CMR) after the 3rd consolidation cycle.

Results
Twenty successful pregnancies occurred, all in patients in CR (2 in second CR), off therapy for a median of 57 months (range 6–120). Nine pregnancies ended with spontaneous vaginal deliveries and 11 by cesarian section; resulting in the birth of 21 live, healthy newborns, without evidence of congenital anomalies. All 21 children showed normal development and growth during their respective follow-up periods; to date they are all in good health, median age 24 months (range 8–54).

Conclusions
The inclusion of ATRA in chemotherapy regimens for the treatment of APL had significantly improved the prognosis, changing the natural history of the disease, by increasing the incidence of CR, resistant disease being virtually absent, prolonging OS and DFS, and improving the quality of the CR, in terms of the hematologic and molecular response. The resulting prolongation of life expectancy allows these patients, mainly those off therapy, to resume their normal life style, including fulfilling a natural desire for children. The low median age at onset increases the probability of pregnancy post-chemotherapy.
The long-term effects of ATRA-including regimens on fertility and on the newborn are not yet known. In our experience, pregnancy is feasible and does not pose additional risks.

Disclosures:
No relevant conflicts of interest to declare.