Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: A case series

Background: With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias.

Objective: To investigate the safety of performing autologous ovarian tissue transplantation in acute leukemia survivors.

Study Design: Clinical, histopathological and molecular data of four women with acute myeloid leukemia and two with acute lymphoblastic leukemia, who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66-100% of an ovarian cortex with a slow freezing method, all women received high dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Prior to the ovarian tissue transplantation: 1) Antral follicle counts, serum AMH and FSH levels were assessed to confirm primary ovarian insufficiency; 2) all recipients were cleared by their hematologist-oncologists; 3) representative cortical strips were screened for leukemia infiltration by histologic (H&E), immunohistochemical (CD3, CD 20, CD34, CD 68, CD 117, CD 163, PAX-5, Tdt, lysozyme, MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate.

Results: The median age was 20 years (15-32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction/consolidation chemotherapy that included ARA-C+ Daunorubicin" or "BFM-95" and were in remission. Mean serum AMH was 1.9±1.7ng/ml before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (range; 41-120 months) following ovarian tissue cryopreservation. Ovarian function resumed in all patients after a mean of 3 months (range 2.5-4 months), and two women of each had one live birth. The median graft longevity was 35.5 months post-ovarian tissue transplantation (18-57 months). After a median follow-up of 51 months (20-74 months), all patients remained relapse-free. In one patient, the graft was removed during cesarean section and was negative for immunochemical leukemia markers.

Conclusion: Our long-term follow-up demonstrated no evidence of disease relapse after ovarian tissue transplantation in patients with acute leukemia who received allogenic hematopoietic stem cell transplantation. This safety profile may be explained by the fact that these patients are induced into remission by non-gonadotoxic induction chemotherapy before undergoing ovarian tissue cryopreservation. We propose that ovarian tissue cryopreservation should not be excluded as a fertility preservation option for young women with leukemia who are due to receive preconditioning chemotherapy prior to allogeneic hematopoietic stem cell transplantation.