Human reproduction (Oxford, England) · 2025
Detection of minimal residual disease in cryopreserved testicular tissue from (pre)pubertal boys with acute leukemia following first-line therapy.
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Feraille Aurélie, Etancelin Pascaline, Troche Shirley, Jardin Fabrice, Buchbinder Nimrod, Schneider Pascale, Dugay Magali, Rives Nathalie, Rondanino Christine, Dumont Ludovic
Аннотация
STUDY QUESTION: Is it feasible to detect minimal residual disease (MRD) in cryopreserved testicular tissue (TT) from (pre)pubertal boys diagnosed with acute leukemia using molecular biology techniques?
SUMMARY ANSWER: This pilot study demonstrates the feasibility of detecting MRD in cryopreserved TT, which could guide the choice of the safest techniques for fertility restoration.
WHAT IS KNOWN ALREADY: Fertility preservation through testicular tissue freezing (TTF) is offered to (pre)pubertal boys undergoing highly gonadotoxic treatment. However, the risk of reintroducing leukemic cells during fertility restoration has not been adequately addressed. To date, no study has evaluated the feasibility of detecting residual disease using molecular biology within cryopreserved, thawed and unfixed TT.
STUDY DESIGN, SIZE, DURATION: This pilot study analyzed cryopreserved TT from 14 (pre)pubertal boys diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) who had already received first-line chemotherapy and underwent TTF before hematopoietic stem cell transplantation.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included cryopreserved TT from 14 (pre)pubertal boys. Molecular biology techniques, including RT-qPCR and qPCR, were used to detect oncogenic fusion genes or clonal rearrangements of immunoglobulin genes or T-cell receptor (Ig/TCR) in cryopreserved TT samples.
MAIN RESULTS AND THE ROLE OF CHANCE: MRD was identified in 36% (5 out of 14) of TT samples using molecular biology techniques. A 21% discordance was observed between conventional histopathology and molecular detection, with molecular methods showing higher sensitivity. No significant association was found between clinical or histological characteristics and MRD status in the TT.
LIMITATIONS, REASONS FOR CAUTION: This study is a pilot study with a small sample size of TT samples from patients with ALL or AML, which may limit the generalizability of the findings. Further studies with larger cohorts are needed to validate our data.
WIDER IMPLICATIONS OF THE FINDINGS: The detection of MRD in cryopreserved TT using molecular biology techniques could help guide the selection of the safest fertility restoration strategies for leukemic patients by minimizing the risk of reintroducing malignant cells. This approach underscores the importance of cryopreserving TT after complete remission of acute leukemia (AL).
STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Rouen University Hospital, GIRCI NO, French Biomedicine Agency, and Ligue National Contre le Cancer. The authors declare no competing interests.
TRIAL REGISTRATION NUMBER: Not applicable.
SUMMARY ANSWER: This pilot study demonstrates the feasibility of detecting MRD in cryopreserved TT, which could guide the choice of the safest techniques for fertility restoration.
WHAT IS KNOWN ALREADY: Fertility preservation through testicular tissue freezing (TTF) is offered to (pre)pubertal boys undergoing highly gonadotoxic treatment. However, the risk of reintroducing leukemic cells during fertility restoration has not been adequately addressed. To date, no study has evaluated the feasibility of detecting residual disease using molecular biology within cryopreserved, thawed and unfixed TT.
STUDY DESIGN, SIZE, DURATION: This pilot study analyzed cryopreserved TT from 14 (pre)pubertal boys diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) who had already received first-line chemotherapy and underwent TTF before hematopoietic stem cell transplantation.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included cryopreserved TT from 14 (pre)pubertal boys. Molecular biology techniques, including RT-qPCR and qPCR, were used to detect oncogenic fusion genes or clonal rearrangements of immunoglobulin genes or T-cell receptor (Ig/TCR) in cryopreserved TT samples.
MAIN RESULTS AND THE ROLE OF CHANCE: MRD was identified in 36% (5 out of 14) of TT samples using molecular biology techniques. A 21% discordance was observed between conventional histopathology and molecular detection, with molecular methods showing higher sensitivity. No significant association was found between clinical or histological characteristics and MRD status in the TT.
LIMITATIONS, REASONS FOR CAUTION: This study is a pilot study with a small sample size of TT samples from patients with ALL or AML, which may limit the generalizability of the findings. Further studies with larger cohorts are needed to validate our data.
WIDER IMPLICATIONS OF THE FINDINGS: The detection of MRD in cryopreserved TT using molecular biology techniques could help guide the selection of the safest fertility restoration strategies for leukemic patients by minimizing the risk of reintroducing malignant cells. This approach underscores the importance of cryopreserving TT after complete remission of acute leukemia (AL).
STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Rouen University Hospital, GIRCI NO, French Biomedicine Agency, and Ligue National Contre le Cancer. The authors declare no competing interests.
TRIAL REGISTRATION NUMBER: Not applicable.