Title

Male-Specific Late Effects in Adult Hematopoietic Cell Transplantation Recipients: A Systematic Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation

Authors

Rachel Phelan, Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: rphelan@mcw.edu.
Annie Im, University of Pittsburgh/UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.
Rebecca L. Hunter, Division of Hematology, University of Colorado Anschutz Medical Center, Aurora, Colorado.
Yoshihiro Inamoto, Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
Maria Teresa Lupo-Stanghellini, Hematology and Bone Marrow Transplantation Unit, IRCC San Raffaele Scientific Institute, Milan, Italy.
Alicia Rovo, Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Sherif M. Badawy, Division of Hematology, Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Linda Burns, Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Hesham Eissa, Department of Pediatrics, Center for Cancer and Blood Disorders, University of Colorado School of Medicine, Aurora, Colorado.
Hemant S. Murthy, Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida.
Pinki Prasad, Department of Pediatrics, Louisiana State University Health Sciences Center/Children's Hospital of New Orleans, New Orleans, Louisiana.
Akshay Sharma, Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
Elizabeth Suelzer, Medical College of Wisconsin, Milwaukee, Wisconsin.
Vaibhav Agrawal, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California.
Mahmoud Aljurf, Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
Karen Baker, Duke University Medical Center, Durham, North Carolina.
Grzegorz W. Basak, University Clinical Centre, Medical University of Warsaw, Warsaw, Poland.
David Buchbinder, Division of Pediatric Hematology, Children's Hospital of Orange County, Orange, California.
Zachariah DeFilipp, Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, Massachusetts.
Lana Desnica Grkovic, University Hospital Centre Zagreb, Croatia.
Ajoy Dias, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Hermann Einsele, Department of Internal Medicine II, Universitätsklinikum Würzburg, Würzburg, Germany.
Michael L. Eisenberg, Department of Urology, Stanford University School of Medicine, Stanford, California.
Narendranath Epperla, Division of Hematology, Department of Medicine, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio.
Nosha Farhadfar, Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, Florida.
Arthur Flatau, Austin, Texas.
Robert Peter Gale, Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
Hildegard Greinix, Division of Hematology, Medical University of Graz, Graz, Austria.
Betty K. Hamilton, Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
Shahrukh Hashmi, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; Department of Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
Peiman Hematti, Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin, Madison, Wisconsin.
Kareem Jamani, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
Dipnarine Maharaj, South Florida Bone Marrow Stem Cell Transplant Institute, Boynton Beach, Florida.

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.

Publication Title

Transplantation and cellular therapy

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