First Delivery in Leukemia Survivor following Ovarian Tissue Cryopreservation (OTCP) and Transplantation Preceded by Evaluation for Leukemia Cells Contamination

Introduction: Chemotherapy induced ovarian failure is common in young leukemia patients undergoing myeloablative conditioning. To preserve fertility, OTCP is often the only option, and is increasingly employed world-wide in such scenarios. Nevertheless, re-transplantations are yet to be described, generally avoided due to an estimated high risk for malignancy introduction.

Aim: Perform a safe, successful autologous ovarian tissue re-transplantation in a sterile AML survivor.

Methods: An AML patient (19y) underwent OTCP during complete remission prior to bone marrow (BM) transplantation. FISH analysis of leukemic cells demonstrated MLL gene aberration within 11-chromosome.Following prolonged amenorrhea (10yrs) the patient desired pregnancy. Laboratory showed AMH < 0.1ng/mL, FSH 116 mIU/ml and LH 88 mIU/ml. Ultrasound revealed no follicles. To consider transplantation, histology, immunohistochemistry, FISH, next generation sequencing (NGS) and SCID mice transplantation were taken to evaluate thawed tissue samples for the presence of leukemia cells.

Results: H&E staining on thawed cortical fragments revealed 93 primordial follicles. CD43 and C-KIT immuno-stains didn’t reveal leukemia cells. Three SCID-mice were grafted with tissue fragments and were weekly followed for 6 months. Macroscopic, and microscopic pathological evaluation did not show leukemia signs. FISH for MLL rearrangement resulted in a read below the probe’s cut-off. NGS panel of 54 genes implicated in myeloproliferative disorders did not reveal any significant molecular event. Following the approval of ethical committee, transplantation was performed, resulting in the delivery of healthy newborn. Two years elapsed since transplantation and patient is leukemia free.

Conclusion: Harvesting during complete remission combined with intense tissue evaluation before transplantation, allowed a safe, successful transplantation in an AML survivor.