First delivery in a leukemia survivor after transplantation of cryopreserved ovarian tissue, evaluated for leukemia cells contamination

Abstract

Objective: To describe a successful autologous ovarian tissue re-transplantation in a sterile leukemia survivor after evaluation for minimal residual disease and provide a review of the current literature.

Design: Presentation of a carefully designed workup taken to evaluate tissue for minimal residual disease, its limitations, and applicability to other patients. To date, there have not been any publications of auto-transplantations in leukemia survivors, owing to an estimated high risk for malignancy induction.

Setting: Large tertiary hospital.

Patient(s): A 19-year-old acute myeloid leukemia patient underwent ovarian tissue cryopreservation during complete remission before bone marrow transplantation. After prolonged amenorrhea, the patient desired pregnancy. Laboratory tests showed antimüllerian hormone <0.1 ng/mL and FSH 116 mIU/mL. Ultrasound revealed no ovarian follicles.

Intervention(s): Ovarian tissue cryopreservation and auto-transplantation. Histology, immunohistochemistry, FISH, next-generation sequencing, and xenotransplantation were done to evaluate thawed tissue samples for the presence of leukemia cells.

Main outcome measure(s): Evidence for leukemia cells in thawed ovarian tissue, reproductive outcomes and live birth after transplantation, and leukemia-free survival.

Result(s): Histology was negative for leukemia cells. Three severe combined immunodeficiency mice, grafted with tissue fragments, were followed for 6 months and showed no macroscopic/microscopic signs for leukemia. Fluorescence in situ hybridization for disease-specific gene rearrangement resulted in a read below the probe's cut-off. A next-generation sequencing panel of genes implicated in myeloproliferative disorders did not reveal any significant molecular event. Transplantation was performed, followed by ovarian stimulation and IVF, resulting in the delivery of healthy newborn. More than 2 years have elapsed since transplantation, and the patient is leukemia free.

Conclusion(s): Harvesting during complete remission, combined with intense tissue evaluation before transplantation, allowed a safe, successful transplantation in an acute myeloid leukemia survivor.

Keywords: Fertility preservation; MRD; OTCP; leukemia; ovarian tissue auto-transplantation.