Minimal residual disease of leukemia and the quality of cryopreserved human ovarian tissue in vitro

Abstract

Auto-transplant of cryopreserved ovarian tissue in leukemia patients carries a risk to reintroduce malignant cells. Maturation of ovarian follicles in vitro is a promising strategy to overcome the leukemic cell contamination. The follicle development and survival in 14 cryopreserved ovarian tissues with leukemia-specific PCR marker was evaluated after 7 or 14 days culture. Minimal residual disease (MRD) quantification was assessed by real-time quantitative PCR in order to identify the MRD positive (n = 6) and negative (n = 8) samples and to monitor levels of MRD before and after culture. The morphology of ovarian follicles were studied by light microscopy. After culture, no statistical significant differences were detected in follicle densities between MRD positive- and negative samples. Ovarian MRD either decreased below undetectable or fluctuated near the baseline level after 7 and 14 days in culture. This study provides quantitative in vitro evidence that leukemia contamination does not affect the follicle survival in cryopreserved ovarian tissue.

Keywords::

• Leukemia
• minimal residual disease
• ovarian tissue
• tissue culture

Acknowledgements

We would like to thank the Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Norway, for donation of the material in this study, Dr Tiina Laine and Sirpa Mäkinen for their contribution in performing the study and Dr Anne Wikström for her contribution in initiating the fertility preservation study, Taija Poikkipuoli and Erica Nyman for skillful technical assistance and Björn Jonsson for help with statistical analysis.

Funding

This research was supported by grants from the Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, Norway, the Swedish Childhood Cancer Foundation, the Finnish Cancer Society, the Finnish Pediatric Research Foundation, the Paulo Foundation, the Väre Foundation for Pediatric Cancer Research, the Academy of Finland, The Swedish Research Council, ALF Stockholm County and the Karolinska Institute.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.