Fertility in Female Patients After Allogeneic Stem Cell Transplantation Following Reduced-Intensity Conditioning (RIC allo-SCT)
Authors: Assouline Emmanuelle , Crocchiolo Roberto , Prebet Thomas , Furst Sabine , El-Cheikh Jean , Florence Broussais , Coso Diane , Charbonnier Aude , Chabannon Christian , Vey Norbert , Marc Gamerre , Blaise Didier , Courbiere Blandine 
Published: October 2019

Abstract
Abstract 3057

Objective
There is only limited data available on women's fertility for younger patients treated by reduced intensity conditioning allogeneic stem cell transplantation (RIC allo-SCT). This issue is important as RIC allo-SCT is a potential curative treatment and as women's fertility preservation methods had improved with now several births after ovarian cryoconservation for example.

Materials and Methods
We evaluate fertility among female patients younger than 35 years old receiving RIC allo-SCT for hematological malignancy or aplastic anemia. This is a single center retrospective study. Informations on therapies before RIC allo-SCT were collected including disease characteristics, previous therapy (chemo, radiotherapy, autologous SCT), and allogeneic transplantation modalities. Data on fertility evaluation after RIC allo-SCT included clinical and biological criteria (see below). Any proposed option of fertility preservation was analyzed as well as any information about potential loss of fertility and/or ovarian failure received by patients before RIC allo-SCT.

Results
Ninety-six patients under the age of 35 underwent RIC allo-SCT between January 2000 and January 2010. Fifty patients are alive at last follow-up, 23 of them are female patients. Twenty-two patients were available for the study. Mean age at last follow-up is 32 (22–46), mean age at diagnosis is 27 (17–35). Median follow-up after RIC allo-SCT is 47 months. Diagnoses were: Hodgkin's lymphoma (36, 4%), Acute myeloid leukemia (22, 7%), aplastic anaemia (13, 6%), Acute lymphoblastic leukemia (9%), multiple myelome (9%), non-Hodgkin's lymphoma (4, 5%), Chronic lymphocytic leukemia (4, 5%). The median number of previous treatment regimen before allo was × (1 line (36.9%), 2 (41%), 3 (9%)). One patient received sub-diaphragmatic radiotherapy at dose of 36Gy and three patients received RIC allo-SCT without prior chemotherapy (AA cases). ASCT followed BEAM or high-dose Melphalan conditioning in 45, 4% of patients. RIC allo-SCT was realized after the following conditioning regimens: cyclophosphamide-ATG (13, 6%), fludarabine-busulfan-ATG (45, 4%), TBI 2Gy +/− Fludarabine + /- Cyclophosphamide (40, 9%). Before RIC allo-SCT 86, 3% of patients had regular menses and 50, 9% had previous pregnancies (1–3). After RIC allo-SCT, amenorrea affects 68% of patients, 87% of whom have menopausal symptoms. All three AA patients have regular cycles and became pregnant after RIC allo-SCT whereas none of the patient treated for hematological malignancy became pregnant. Biological hormonal evaluation showed impaired ovarian function for 82% of the patients with elevated LH and FSH values and low Oestradiol and Anti Mullerian Hormon values. On a more general aspect, Only six (27, 2%) patients declared to have been correctly informed before RIC allo-SCT on potential deleterious effects on fertility by anticancer treatment; five (22, 7%) patients declared to have been partially informed and 11 (50%) not informed at all, respectively. Fertility preservation was proposed to five patients before RIC allo-SCT: 2 refused, 2 had in vitro fecundation and 1 had ovarian cryopreservation.

Conclusion
This is the first study specifically focusing on fertility after RIC allo-SCT among young female patients. Results show a high rate of ovarian failure, evaluated by both clinical and biological criteria. The significant difference here between AA and malignant diseases suggests that a potential deleterious role was played by previous anticancer treatments including HD chemotherapy followed by auto SCT rather than by RIC allo-SCT itself.

Disclosures:
No relevant conflicts of interest to declare.