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

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. 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, while conventional chemotherapy is associated with a low risk of infertility. Thus, fertility preservation is highly recommended in young patients before HSCT. Testicular tissue cryopreservation (TTC) is the only option offered to prepubertal or peripubertal patients, with the perspective of restoring fertility from the spermatogonia contained in the immature tissue. Our study presents the largest series published to date about the testicular tissue content of spermatogonia in young patients with AL after administration of first-line chemotherapies. It shows that non-alkylating chemotherapies administered before TTC do not significantly reduce the spermatogonial pool. Our work also confirms in a large population that CCD over 4 g/m² causes sharp depletion of the spermatogonial pool. This study provides new valuable information regarding the reproductive potential of testicular tissue collected before HSCT from children with AL previously exposed to first-line chemotherapies including alkylating agent or not. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement A-S.G. was supported by a grant from the ARC Fondation pour la Recherche contre le Cancer (DOC20180507400). The human Spermatogonial Stem Cell research project (A.-S.G., C.L., L.R., J.-P.W., P.F., and V.B.-L.) was funded by grants from the Agence de Biomedecine and Electricite De France. It also received funding from the Laurette Fugain and the EGMOS Associations. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Research Ethics Committee of Cochin Hospital, Paris, France (AAA-2019-08014) and was conducted in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors