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. They 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 between transplant 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 utilized 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. We therefore recommend to systematically screen for male genital GvHD regularly and report it to large registries to allow for a better understanding. Future research should also address treatment since little published evidence is available to date. Male-specific endocrine consequences of HCT include hypogonadism which may also affect bone health. Since the evidence is scarce, 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, which warrants offering sperm preservation in all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, hence 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 than in the general population; however, subsequent malignancies in general seem to be more prevalent in males than females, and special attention should be given to skin and oral mucosa.
Male-specific late effects, probably more under-reported 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 transplant physicians and specialists from other involved disciplines. Future research should be directed towards better data collection on male-specific late effects and on studies about the interrelationship between these late effects, to allow the development of evidence based effective management practices.
Transplantation and cellular therapy. 2021 Oct 29 [Epub ahead of print]
Rachel Phelan, Annie Im, Rebecca L Hunter, Yoshihiro Inamoto, Maria Teresa Lupo-Stanghellini, Alicia Rovo, Sherif M Badawy, Linda Burns, Hesham Eissa, Hemant S Murthy, Pinki Prasad, Akshay Sharma, Elizabeth Suelzer, Vaibhav Agrawal, Mahmoud Aljurf, Karen Baker, Grzegorz W Basak, David Buchbinder, Zachariah DeFilipp, Lana Desnica Grkovic, Ajoy Dias, Hermann Einsele, Michael L Eisenberg, Narendranath Epperla, Nosha Farhadfar, Arthur Flatau, Robert Peter Gale, Hildegard Greinix, Betty K Hamilton, Shahrukh Hashmi, Peiman Hematti, Kareem Jamani, Dipnarine Maharaj, John Murray, Seema Naik, Sunita Nathan, Steven Pavletic, Zinaida Peric, Drazen Pulanic, Richard Ross, Andrea Salonia, Isabel Sanchez-Ortega, Bipin N Savani, Tal Schechter, Ami J Shah, Stephanie M Smith, John A Snowden, Amir Steinberg, Douglas Tremblay, Sarah C Vij, Lauren Walker, Daniel Wolff, Jean A Yared, Hélène Schoemans, André Tichelli
CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI;; Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI;. Electronic address: ., University of Pittsburgh/UPMC Hillman Cancer Center, Pittsburgh, PA., Division of Hematology, University of Colorado Anschutz Medical Center, Aurora, CO., Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan., Hematology and Bone Marrow Transplantation Unit, IRCC San Raffaele Scientific Institute, Milano, Italy., Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern., Division of Hematology, Oncology and Stem Cell Transplant, Ann & Robert H. 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