Cryopreserved ovarian tissue autotransplantation in an acute myeloid leukaemia survivor following extensive minimal residual disease screening: first reported live birth in Europe.
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PURPOSE: We report successful autotransplantation of ovarian tissue in a sterile acute myeloid leukaemia survivor after comprehensive minimal residual disease (MRD) screening. METHODS: At age 18, the patient underwent ovarian tissue cryopreservation while in complete remission prior to allogeneic stem cell transplantation. Premature ovarian failure and the wish to conceive led her to request transplantation of her cryopreserved ovarian tissue 12 years later. Extensive MRD screening of frozen-thawed biopsy specimens, including histology, immunohistochemistry, PCR and 6-month xenotransplantation to immunodeficient mice, was conducted before ovarian tissue transplantation (OTT). RESULTS: Histology and immunohistochemistry (MPO, p53, CD4, CD45) of thawed ovarian fragments showed no malignant cell contamination. Nested RT-PCR (MLL::AF9) was negative and the mouse grafted with ovarian tissue showed no disease after 6 months. The xenografted tissue was analyzed again (histology, immunohistochemistry and RT-PCR) and showed no contamination. Laparoscopic transplantation to the patient restored ovarian function after 4 months. Modified natural cycle IVF resulted in pregnancy. At 29 weeks, the patient had preterm premature rupture of membranes and delivered a healthy boy at 34.5 weeks. Three years post-transplantation, the patient remains disease-free. CONCLUSIONS: Concerns about malignant cell contamination limit cryopreserved OTT in leukemia survivors. This is the first reported European live birth in an acute myeloid leukemia survivor following frozen-thawed OTT. Safe OTT was achieved by retrieving ovarian tissue during complete remission and conducting thorough screening before transplantation. Obstetrical risks in leukemia survivors who had total body irradiation should also be thoroughly discussed during decision making before attempting motherhood.