Outcome Of Pregnancy After Autologous Hematopoietic Stem Cell Transplantation (AHSCT) For Autoimmune Diseases (AD): A Retrospective Study Of The EBMT Autoimmune Diseases Working Party (ADWP)
Authors: Snarski Emilian , Snowden John A , Badoglio Manuela , Carlson Kristina , Burman Joachim , Oliveira Maria Carolina , Moore John , Tan Jeffrey , Rovira Montserrat , Clark Richard E , Saiz Albert , Khelifa Sondess Hadj , Crescimanno Alessandra , Laing Lynne , Musso Maurizio , Martin Thierry , Farge Dominique 
Published: October 2019

Introduction
AHSCT is increasing used to control severe and refractory autoimmune diseases (AD). Many patients (pts) are women of reproductive age with a potential desire for pregnancy, especially with control of AD. However, high dose cytotoxic therapy is associated with an age dependent risk of temporary or permanent ovarian and/or endometrial damage. Although childbirth has been sporadically reported after AHSCT for AD, the incidence, complications and outcomes of pregnancy in this group have never been characterised. We present the first multicenter retrospective analysis of pregnancy in patients who underwent AHSCT for AD.

Patients and Methods
The study was designed as a multicenter retrospective study of data registered in the EBMT database with supplementary information requested with a specific questionnaire sent to each centre. Inclusion criteria were: female pts aged >18 and 50 years receiving AHSCT for AD between 1994-2011. Over this time period 588 adult female patients fulfilling inclusion criteria were identified in the EBMT database and collaborating centres.

Results
Twenty-two pregnancies were reported in 15 pts between 1997-2010 2013, with 4 pts having 2 pregnancies, and one pt having 4 pregnancies, amounting to approximately 2% of total eligible registrations. Indications for AHSCT included multiple sclerosis (7 pts), systemic sclerosis (5 pts), rheumatoid Arthritis (1 pt), juvenile idiopathic arthritis (1 pt) and Takayasu disease (1 pt). All pts had received standard immunosuppressive +/- cytotoxic treatment for AD prior to mobilisation and AHSCT. The most common mobilization regimen was cyclophosphamide (2-4g/m2) and G-CSF. Conditioning for AHSCT was high dose cyclophosphamide (200mg/kg) in 7 pts, BEAM in 7 pts and one pt received BCNU (300mg/m2) with cyclophosphamide (150g/kg). Serotherapy was used in 10 patients (ATG in 9, ALG in 1). None received TBI. Of the 22 reported pregnancies, 20 were due to natural conception and 2 required assisted conception (two with in vitro fertilization). Fifteen pregnancies (68%) were successful, while seven (38%) were unsuccessful due to ectopic pregnancy (n=1), spontaneous abortion (n=4), and spontaneous fetal death (n=1). and induced abortion (n=1). Other serious adverse events included gestational diabetes mellitus (n=1), congestive heart failure and atrial fibrillation (n=1) and pre-term labor (n=1). Five serious adverse events occurred during first pregnancies, and 2 during second pregnancies. Exacerbations of AD occurred in 2 pts during second pregnancies. In all other patients the AD remained stable throughout pregnancy and post-partum. No maternal mortality was associated with pregnancy or post-partum. The status of the AD at most recent follow up was reported as remission (5 pts), improvement (4 pts), stabilization (3 pts), progression (2 pts) and 1 death due to AD progression. There were no reports of congenital, developmental or any other disease in the children of these pregnancies.

Discussion
This retrospective analysis confirms that pregnancy is feasible in some pts following AHSCT for severe AD. The outcome of pregnancy is generally good and most lead to the birth of healthy children. It is unclear whether the reported rates of adverse obstetric events exceed that of the general population, but exacerbation of underlying autoimmune disorder is possible. In pts who have undergone AHSCT for AD who wish to plan a pregnancy, we recommend close interdisciplinary collaboration involving obstetricians and relevant AD specialists. However, the reported frequency of pregnancy was relatively rare, and we continue to recommend consideration of embryo or ovum cryopreservation prior to AHSCT as per current ADWP guidelines (Snowden et al BMT 2012;47:770-90)

Disclosures:
No relevant conflicts of interest to declare.