Abstract
Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GVHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. These effects may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Here we provide a systematic review of male-specific late effects in a collaboration among transplantation physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. We used a systematic review methodology to summarize incidence, risk factors, screening, prevention, and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Most of the evidence regarding male GVHD is still based on limited data, precluding strong therapeutic recommendations. Therefore, we recommend systematic screening for male genital GVHD regularly and reporting of cases to large registries to allow for a better understanding. Future research also should address treatment, given the little published evidence currently available. Male-specific endocrine consequences of HCT include hypogonadism, which also may affect bone health. Given the scanty evidence, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases, and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, warranting the offer of sperm preservation for all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, underscoring the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent in HCT recipients compared with the general population; however, subsequent malignancies in general seem to be more prevalent in males than in females, and special attention should be given to skin and oral mucosa. Male-specific late effects, which likely are more underreported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplantation physicians and specialists from other involved disciplines. Future research should be directed toward better data collection on male-specific late effects and on studies about the interrelationships among these late effects, to allow the development of evidence-based effective management practices.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 335.e1-335.e17 |
| Journal | Transplantation and Cellular Therapy |
| Volume | 28 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2022 |
Funding
R.P. reports research funding from Amgen. H.E. reports grants and Hermann Einsele – reports Honorarium, Adv. Board with Takeda from BMS/Celgene, Janssen, Amgen, Sanofi, and GSK and other from Takeda during the conduct of the study. S.H. reports Shahrukh Hashmi – reports Advisory Board, Travel Grants, Educational Activities with Pfizer, Novartis, Therakos, Janssen and MSD from Pfizer, Novartis, Therakos, Janssen, and MSD outside the submitted work. Y.I. reports personal fees from Novartis, Janssen, and Meiji Seika Pharma outside the submitted work. R.R. reports Richard Ross – reports Director with Diurnal Plc from Diurnal during the conduct of the study. H.S. reports participation in advisory boards for Janssen and Novartis; speaker's fees from Incyte, Jazz Pharmaceuticals, Takeda, Novartis and the Belgian Hematological Society; travel grants from the EBMT, CIBMTR, Incyte, and Gilead; and research funding from Novartis and the Belgian Hematological Society outside of the submitted work. A.R. reports grants from Novartis, CSL Behring, and Alexion; personal fees from Novartis, BMS, and OrPha Swiss; and Alicia Rovo – reports financial support for congresses and conferences with Amgen, AstraZeneca, Sanofi and Celgene from Amgen, AstraZeneca, Sanofi, and Celgene outside the submitted work. A.S. reports grants from CRISPR Therapeutics, payment or honoraria from Vindico Medical Education, and personal consultancy fees from Spotlight Therapeutics and Medexus outside the submitted work. J.A.S. reports personal fees from Medac, Kiadis, Gilead, Janssen, Mallinckrodt, Jazz Pharmaceutical, and Actelion outside the submitted work. D.W. reports grants and personal fees from Novartis and personal fees from Mallinckrodt and Behring, outside the submitted work. R.P.G. serves as a consultant for Ascenage Pharma, BeiGen, Kite Pharma, Fusion Pharma, LaJolla NanoMedical, MingSight Pharmaceuticals, and CStone Pharmaceuticals; is the medical director for FFF Enterprises; is a partner in AZCA; serves on the board of directors of the RakFond Foundation for Cancer Research Support; and serves on scientific advisory boards for Antegene Biotech and StemRad. A.J.S. serves on medical advisory boards for Rocket Pharmaceuticals and Orchard Pharmaceuticals. N.E. serves on speaker's bureaus for Verastem and Beigene and on an advisory board for Karyopharm and has received an honorarium for Genzyme outside of the submitted work. Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute (NCI), National Heart, Lung and Blood Institute (NHLBI), and National Institute of Allergy and Infectious Diseases (NIAID); Grant HHSH250201700006C from the Health Resources and Services Administration (HRSA); and Awards N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and the following commercial entities: AbbVie, Accenture, Actinium Pharmaceuticals, Adaptive Biotechnologies, Adienne SA, AlloVir, Amgen, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, CareDx, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Eurofins Viracor, ExcellThera, Fate Therapeutics, Gamida Cell, Genentech; Gilead, GlaxoSmithKline, Incyte, Janssen/Johnson & Johnson, Jasper Therapeutics, Jazz Pharmaceuticals, Karyopharm Therapeutics, Kiadis Pharma; Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Medac, Merck & Co, Millennium, Miltenyi Biotec, MorphoSys, Novartis Pharmaceuticals, Omeros, Oncopeptides, Orca Biosystems, Ossium Health, Pfizer, Pharmacyclics, Priothera, Sanofi Genzyme, Seagen, Stemcyte, Takeda Pharmaceuticals, Tscan, Vertex, Vor Biopharma, and Xenikos BV.
Keywords
- Chronic graft-versus-host disease
- Genital
- Hematopoietic cell transplantation
- Hypogonadism
- Infertility
- Late effects
- Male-specific
- Sexual dysfunction
- Subsequent malignancies
- Survivorship
ASJC Scopus subject areas
- Immunology and Allergy
- Molecular Medicine
- Hematology
- Cell Biology
- Transplantation
