Male Gonadal Function After Pediatric Hematopoietic Stem Cell Transplantation: A Systematic Review.


Journal

Transplantation and cellular therapy
ISSN: 2666-6367
Titre abrégé: Transplant Cell Ther
Pays: United States
ID NLM: 101774629

Informations de publication

Date de publication:
08 2022
Historique:
received: 27 01 2022
revised: 08 04 2022
accepted: 23 05 2022
pubmed: 2 6 2022
medline: 4 8 2022
entrez: 1 6 2022
Statut: ppublish

Résumé

Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development, sexual dysfunction, and infertility. However, no systematic review exists regarding prevalence and risk factors in relation to different treatment regimens. We aimed to systematically evaluate the current evidence regarding the prevalence of male gonadal dysfunction after pediatric HSCT, related risk factors, and the diagnostic value of surrogate markers of spermatogenesis in this patient group. We searched PubMed and Embase using a combination of text words and subject terms. The eligibility screening was conducted using predefined criteria. Data were extracted corresponding to the Leydig cell compartment involved in testosterone production and the germ cell compartment involved in spermatogenesis, respectively. Subsequently, data synthesis was performed. Of 2369 identified records, 25 studies were eligible. The studies were heterogeneous in terms of included diagnoses, gonadotoxic therapy, follow-up time, and definitions of gonadal dysfunction. The data synthesis revealed a preserved Leydig cell function in patients treated with non-total body irradiation (TBI) regimens, whereas the evidence regarding the impact of TBI conditioning on Leydig cell function was conflicting. Based on surrogate markers of spermatogenesis and only limited data on semen quality, the germ cell compartment was affected in half of the patients treated with non-TBI regimens and in nearly all patients treated with TBI conditioning. Testicular irradiation as part of front-line therapy before referral to HSCT led to complete Leydig cell failure and germ cell failure. Evidence regarding the impact of diagnosis, pubertal stage at HSCT, and chronic graft-versus-host disease is limited, as is the evidence of the diagnostic value of surrogate markers of spermatogenesis. Testicular irradiation as part of front-line therapy and TBI conditioning are the main risk factors associated with male gonadal dysfunction after pediatric HSCT; however, impaired spermatogenesis is also observed in half of the patients treated with non-TBI regimens. Methodological shortcomings limit existing evidence, and future studies should include semen quality analyses, follow-up into late adulthood, and evaluation of the cumulative exposure to gonadotoxic therapy.

Identifiants

pubmed: 35644480
pii: S2666-6367(22)01330-6
doi: 10.1016/j.jtct.2022.05.036
pii:
doi:

Types de publication

Journal Article Systematic Review Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

503.e1-503.e15

Informations de copyright

Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement There are no conflicts of interest to report.

Auteurs

Sidsel Mathiesen (S)

Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark. Electronic address: sidsel.mathiesen@regionh.dk.

Liv Andrés-Jensen (L)

Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Malene Mejdahl Nielsen (MM)

Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Kaspar Sørensen (K)

Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Marianne Ifversen (M)

Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Kirsi Jahnukainen (K)

New Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; NORDFERTIL Research Lab Stockholm, Department of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.

Anders Juul (A)

Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Klaus Müller (K)

Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

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