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First-line chemotherapies administered before hematopoietic cell transplantation in children with acute leukemia: effect on the spermatogonial pool

Bone Marrow Transplantation volume 60, pages 927–931 (2025)Cite this article

Subjects

Approximately 20% of pediatric patients presenting with acute leukemia (AL) receive an allogeneic hematopoietic stem cell transplantation (HSCT) either in the first or subsequent complete remission [1]. Survivors are exposed at adulthood to fertility impairment, which is one of the most worrisome long-term side effects of pre-HSCT myeloablative conditioning regimens [2], while conventional chemotherapy is associated with a low risk of infertility [3]. Thus, fertility preservation is highly recommended in young patients before HSCT [4]. Testicular tissue cryopreservation (TTC) is the only option offered to prepubertal patients, with the perspective of restoring fertility from the spermatogonia contained in the immature tissue. Previous studies on 37 patients have reported that, despite the low risk on fertility, first-line AL treatments containing alkylating agents have a deleterious effect on the spermatogonial pool, impairing the potential success of fertility restoration programs using cryopreserved testicular tissue [5]. Cyclophosphamide has been reported to be the most gonadotoxic agent on spermatogonia, although data concerning other non-alkylating drugs commonly used in AL therapies are extremely scarce and contradictory [6,7,8].

In our center, prepubertal patients with AL are offered TTC before HSCT, i.e., after front-line chemotherapies containing alkylating agents in ALL and alkylating agents-free in AML. The systematic histological analysis of one testicular tissue fragment we performed to look for malignant cells gives the opportunity to characterize the effect of those therapies on spermatogonia. The objective of our study was to report the effect of alkylating and non-alkylating drugs of first-line chemotherapies administered in children with AL on the spermatogonial pool of testicular tissue collected before HSCT.

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Data availability

The datasets generated during and analyzed during the current study are not publicly available due to French restricted law on electronic personal medical data. These data are available from the corresponding author on reasonable request.

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Acknowledgements

Our sincere thanks to the HISTIM platform of the Cochin Institute, where some of the immunostainings were performed, and some of the tissue slides were scanned. We are also grateful to Danielle Cesari, Anicée Crouzil, Lilia Grira, Corinne Journo, Marie Carmen Rosso, and Cécile Thiebaut Monneret, who performed the TTC in our fertility center.

Funding

SG was supported by a grant from the ARC Fondation pour la Recherche contre le Cancer (DOC20180507400). The human Spermatogonial Stem Cell research project (A-SG, CL, LR, J-PW, PF, and V.B-L) was funded by grants from the Agence de Biomédecine and Électricité De France. It also received funding from the Laurette Fugain and the EGMOS Associations.

Author information

Author notes

  1. These authors contributed equally: A. S. Gille, L. Lenez. C. Poirot, V. Barraud-Lange.

Authors and Affiliations

  1. University Paris Cité, Paris, France

    A. S. Gille, J. H. Dalle, M. Peycelon, M. Sibony, C. Patrat, J. P. Wolf & N. Boissel

  2. Team From Gametes To Birth. Departments Genetic and cellular plasticity. Metabolism and endocrinology. Cochin Institute, INSERM U1016, Paris, France

    A. S. Gille, L. Lenez, C. Chenouf, C. Chalas, C. Patrat, J. P. Wolf & V. Barraud-Lange

  3. AP-HP.Center-University Paris Cité. Cochin Hospital. Department of Reproductive Biology CECOS, Paris, France

    A. S. Gille, C. Chalas, C. Patrat, J. P. Wolf, C. Poirot & V. Barraud-Lange

  4. Gustave Roussy. Department of pediatric and adolescent oncology, Villejuif, France

    L. Lenez

  5. Sorbonne Paris North University, Interdisciplinary Research Institute on Social issues (IRIS), UMR 8156-997, Aubervilliers, France

    A. Vanhæsebrouck

  6. AP-HP, Jean-Verdier Hospital, Department of legal and social Medicine, 93140, Bondy, France

    A. Vanhæsebrouck

  7. Sorbonne University, INSERM, Pierre Louis Institute of Epidemiology and Public Health, Department of Social Epidemiology, Paris, France

    A. Vanhæsebrouck

  8. AP-HP. Sorbonne University. Tenon Hospital. Department of Reproductive Biology CECOS, Paris, France

    D. Rivet-Danon

  9. Paris Cité University, CEA, Genetic Stability, Stem Cells and Radiation, Laboratory of Germinal Stem Cells, Fontenay-aux-, Roses, France

    C. Lapoujade, L. Riou & P. Fouchet

  10. Paris-Saclay University, CEA, Genetic Stability, Stem Cells and Radiation, Laboratory of Germinal Stem Cells, Fontenay-aux-, Roses, France

    C. Lapoujade, L. Riou & P. Fouchet

  11. APHP.North-University Paris Cité. Robert Debré University Hospital. Department of Pediatric Immunology and Hematology, Paris, France

    J. H. Dalle, K. Yakouben & M. Fahd

  12. APHP.North-University Paris Cité. Robert Debré University Hospital. Department of Pediatric Surgery and Urology. Centre de Référence des Malformations Rares des Voies Urinaires (MARVU), ERN eUROGEN accredited center, Inserm UMR 1141 NeuroDev, Paris, France

    M. Peycelon & A. Paye-Jaouen

  13. Sorbonne University, Paris, France

    G. Leverger, H. Boutroux, S. Irtan & C. Poirot

  14. AP-HP.Sorbonne University. Armand Trousseau Hospital. Department of Pediatric Onco-Hematology, Paris, France

    G. Leverger, M. D. Tabone, H. Boutroux & C. Poirot

  15. AP-HP.Sorbonne University. Armand Trousseau Hospital. Department of Visceral Pediatric Surgery, Paris, France

    S. Irtan

  16. AP-HP.Center-University Paris Cité. Cochin Hospital, Paris, France

    M. Sibony

  17. AP-HP.North-University Paris Cité. Saint-Louis Hospital. Department of Hematology, Adolescents and Young Adults Unit, Paris, France

    N. Boissel & V. Barraud-Lange

Authors
  1. A. S. Gille
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  2. L. Lenez
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  3. A. Vanhæsebrouck
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  4. D. Rivet-Danon
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  5. C. Lapoujade
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  6. L. Riou
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  7. J. H. Dalle
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  8. K. Yakouben
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  9. M. Peycelon
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  10. M. Fahd
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  11. A. Paye-Jaouen
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  13. M. D. Tabone
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  15. S. Irtan
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  16. C. Chenouf
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  17. M. Sibony
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  18. C. Chalas
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  19. C. Patrat
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  20. J. P. Wolf
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  21. N. Boissel
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  22. P. Fouchet
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  23. C. Poirot
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  24. V. Barraud-Lange
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Contributions

GAS, LC, RL, FP and BLV designed and performed the experiments; LL, CheC and RDD collected the clinical data. VA performed the statistical analyses; GAS, BLV, PoC, LL, VA and BN interpreted the data; GAS, BLV, LL and PoC were in charge of the preparation, drafting, and editing of the manuscript; PoC and CC performed the fertility preservation counselling for the patients; DJH, YK, MF, GL, TMD, BH referred the patients to the fertility preservation consultation as referring physicians. PM, PJA and IS performed the testicular retrieval. SM performed the systematic anatomopathological analysis and gave access to the biological material to perform the study. PaC and WJP critically reviewed the manuscript, and all of the authors agreed to the final version of the manuscript.

Corresponding author

Correspondence to V. Barraud-Lange.

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The authors declare no competing interests.

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Parents (or Legal guardians) provided their informed consent for the use of their children’s medical data in the present study.

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Gille, A.S., Lenez, L., Vanhæsebrouck, A. et al. First-line chemotherapies administered before hematopoietic cell transplantation in children with acute leukemia: effect on the spermatogonial pool. Bone Marrow Transplant 60, 927–931 (2025). https://doi.org/10.1038/s41409-025-02547-9

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