Keywords
Neoplasms
Skin neoplasms
Kaposi sarcoma
Lymphoproliferative disorders
Chronic kidney disease
How to Cite
Abstract
Background: Kidney transplantation (KT) is the preferred modality of kidney replacement therapy (KRT) for patients with end-stage chronic kidney disease (CKD). However, it is associated with a significantly increased risk of neoplasms, which are the third leading cause of morbidity and mortality in this population, following infections and cardiovascular disease. The incidence of post-transplant neoplasms is approximately 10 times higher than in the general population and tends to follow a more aggressive course. International reports indicate incidence rates ranging from 3.9% to 14.9%. The most frequently reported neoplasms include non-melanoma skin cancer (NMSC), Kaposi's sarcoma (KS), and post-transplant lymphoproliferative disorder (PTLD), with cervical cancer considered a probable additional association.
Purpose: To describe the incidence, distribution, and characteristics of neoplasms in a Colombian cohort of kidney transplant recipients over a 30-year follow-up period.
Methodology: Retrospective observational study of 4572 kidney transplant recipients from 1993 to 2023. Clinical and oncologic variables were analyzed using frequencies, percentages, means or medians as appropriate. Student’s t-test or Mann-Whitney U, and chi-square or Fisher’s exact tests were applied. Cancer-free survival was estimated using Kaplan-Meier curves and compared with the log-rank test. A p-value < 0.05 was considered statistically significant.
Results: A total of 278 neoplasms were identified, yielding an overall incidence of 6%. Squamous cell carcinoma accounted for 24.4% of cases, basal cell carcinoma for 20.5%, PTLD for 11.5%, KS for 9%, and cervical cancer for 8.27%. These five malignancies made up 73.7% of all cases. The remaining 26.3% included other cancers such as prostate, bladder, stomach, colon, thyroid, breast, and clear cell renal carcinoma. KS, PTLD, and cervical cancer typically presented early (within the first 60 months post-transplant), while NMSC showed a later onset. The median time from transplantation to cancer diagnosis was 56 months (IQR: 24-93).
Conclusions: Post-kidney transplant neoplasms are frequent, often display aggressive clinical behavior, and significantly impact both patient quality of life and graft survival. Our findings underscore the need for comprehensive screening, prevention, and cancer management strategies in this population, through a multidisciplinary approach tailored to the local context.
References
Gutiérrez-Dalmau A, Revuelta I, Campistol JM. Renal transplantation and cancer: focus on immunosuppressive therapy. Trends Transplant. 2007;1:3-14.
Lanza LL, Wang L, Simon TA, Irish WD. Epidemiologic critique of literature on post-transplant neoplasms in solid organ transplantation. Clin Transplant. 2009;23(5):582-8. https://doi.org/10.1111/j.1399-0012.2009.01061.x
Gallagher MP, Kelly PJ, Jardine M, Perkovic V, Cass A, Craig JC, et al. Long-term cancer risk of immunosuppressive regimens after kidney transplantation. J Am Soc Nephrol. 2010;21(5):852-8. https://doi.org/10.1681/asn.2009101043
Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant. 2004;4(6):905-13. https://doi.org/10.1111/j.1600-6143.2004.00450.x
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. https://doi.org/10.3322/caac.21387
Farrugia D, Mahboob S, Cheshire J, Begaj I, Khosla S, Ray D, et al. Malignancy-related mortality following kidney transplantation is common. Kidney Int. 2014;85(6):1395-403. https://doi.org/10.1038/ki.2013.458
ANZDATA Registry. 39th Report, Chapter 10: cancer [internet]. Adelaide, Australia: Australia and New Zealand Dialysis and Transplant Registry; 2017. [citado 2017 jun. 15]. Disponible en: https://www.anzdata.org.au/wp-content/uploads/2018/04/c10_cancer_v2.0_20170418.pdf
Acuna SA, Fernandes KA, Daly C, Hicks LK, Sutradhar R, Kim SJ, et al. Cancer mortality among recipients of solid-organ transplantation in Ontario, Canada. JAMA Oncol. 2016;2(4):463-9. https://doi.org/10.1001/jamaoncol.2015.5137
D'Arcy ME, Coghill AE, Lynch CF, Koch LA, Li J, Pawlish KS, et al. Survival after a cancer diagnosis among solid organ transplant recipients in the United States. Cancer. 2019;125(6):933-42. https://doi.org/10.1002/cncr.31782
Brattström C, Granath F, Edgren G, Smedby KE, Wilczek HE. Overall and cause-specific mortality in transplant recipients with a pretransplantation cancer history. Transplantation. 2013;96(3):297-305. https://doi.org/10.1097/tp.0b013e31829854b7
Campistol JM, Cuervas-Mons V, Manito N, Almenar L, Arias M, Casafont F, et al. New concepts and best practices for management of pre- and post-transplantation cancer. Transplant Rev. 2012;26(4):261-79. https://doi.org/10.1016/j.trre.2012.07.001
Na R, Grulich AE, Meagher NS, McCaughan GW, Keogh AM, Vajdic CM. De novo cancer-related death in Australian liver and cardiothoracic transplant recipients. Am J Transplant. 2013;13(5):1296-304. https://doi.org/10.1111/ajt.12192
Yanik EL, Nogueira LM, Koch L, Copeland G, Lynch CF, Pawlish KS, et al. Comparison of cancer diagnoses between the US solid organ transplant registry and linked central cancer registries. Am J Transplant. 2016;16(10):2986-93. https://doi.org/10.1111/ajt.13818
ANZDATA Registry. 39th Report, chapter 8: transplantation [internet]. Adelaide, Australia: Australia and New Zealand Dialysis and Transplant Registry; 2017. [citado 2017 jun. 15]. Disponible en: https://www.anzdata.org.au/wp-content/uploads/2018/04/c08_transplantation_v3.0_20170424.pdf
Robson R, Cecka JM, Opelz G, Budde M, Sacks S. Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil. Am J Transplant. 2005;5(12):2954-60. https://doi.org/10.1111/j.1600-6143.2005.01125.x
Unger JM, Hershman DL, Fleury ME, Vaidya R. Association of patient comorbid conditions with cancer clinical trial participation. JAMA Oncol. 2019;5(3):326-33. https://doi.org/10.1001/jamaoncol.2018.5953
Au EH, Chapman JR, Craig JC, Lim WH, Teixeira-Pinto A, Ullah S, et al. Overall and site-specific cancer mortality in patients on dialysis and after kidney transplant. J Am Soc Nephrol. 2019;30(3):471-80. https://doi.org/10.1681/asn.2018090906
Kauffman HM, Cherikh WS, McBride MA, Cheng Y, Hanto DW. Deceased donors with a past history of malignancy: an organ procurement and transplantation network/united network for organ sharing update. Transplantation. 2007;84(2):272-4. https://doi.org/10.1097/01.tp.0000267919.93425.fb
Ison MG, Nalesnik MA. An update on donor-derived disease transmission in organ transplantation. Am J Transplant. 2011;11(6):1123-30. https://doi.org/10.1111/j.1600-6143.2011.03493.x
UNOS. Data and trends [internet]. Estados Unidos: UNOS; 2011. [citado 2023 jul. 01]. Disponible en: https://unos.org/data/
ONT. Organización Nacional de Trasplantes [internet]. España: ONT. [citado 2023 jul. 01]. Disponible en: www.ont.es
Kauffman HM, McBride MA, Cherikh WS, Spain PC, Delmonico FL. Transplant tumor registry: donors with central nervous system tumors1. Transplantation. 2002;73(4):579-82. https://doi.org/10.1097/00007890-200202270-00017
Nalesnik MA, Woodle ES, Dimaio JM, Vasudev B, Teperman LW, Covington S, et al. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant. 2011;11(6):1140-7. https://doi.org/10.1111/j.1600-6143.2011.03565.x
Wong G, Chapman JR. Cancers after renal transplantation. Transplant Rev. 2008;22(2):141-9. https://doi.org/10.1016/j.trre.2007.12.004
Santos Sampaio M, Cho YW, Qazi Y, Bunnapradist S, Hutchinson IV, Shah T. Posttransplant malignancies in solid organ adult recipients: an analysis of the U.S. National Transplant Database. Transplantation. 2012;94(10):990-8. https://doi.org/10.1097/tp.0b013e318270bc7b
Garrett GL, Blanc PD, Boscardin J, Abramson Lloyd A, Ahmed RL, Anthony T, et al. Incidence of and risk factors for skin cancer in organ transplant recipients in the United States. JAMA Dermatol. 2017;153(3):296-303. https://doi.org/10.1001/jamadermatol.2016.4920
Kang W, Sampaio MS, Huang E, Bunnapradist S. Association of pretransplant skin cancer with posttransplant malignancy, graft failure, and death in kidney transplant recipients. Transplantation. 2017;101(6):1303-9. https://doi.org/10.1097/tp.0000000000001286
Verghese PS, Schmeling DO, Knight JA, Matas AJ, Balfour HH. The impact of donor viral replication at transplant on recipient infections posttransplant: a prospective study. Transplantation. 2015;99(3):602-8. https://doi.org/10.1097/tp.0000000000000354
Piselli P, Busnach G, Citterio F, Frigerio M, Arbustini E, Burra P, et al. Risk of Kaposi sarcoma after solid-organ transplantation: multicenter study in 4,767 recipients in Italy, 1970-2006. Transplant Proc. 2009;41(4):1227-30. https://doi.org/10.1016/j.transproceed.2009.03.009
Gutiérrez-Dalmau A, Campistol JM. Kaposi’s sarcoma after renal transplantation. N Engl J Med. 2005;353(8):846-7.
Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med. 2005;352(13):1317-23. https://doi.org/10.1056/nejmoa042831
Hibberd AD, Trevillian PR, Wlodarczyk JH, Kemp DG, Stein AM, Gillies AHB, et al. Effect of immunosuppression for primary renal disease on the risk of cancer in subsequent renal transplantation: a population-based retrospective cohort study. Transplantation. 2013;95(1):122-7. https://doi.org/10.1097/tp.0b013e3182782f59
Musquera M, Pérez M, Peri L, Esforzado N, Sebastiá MC, Paredes D, et al. Kidneys from donors with incidental renal tumors: should they be considered acceptable options for transplantation? Transplantation. 2013;95(9):1129-33. https://doi.org/10.1097/tp.0b013e3182875e00
Acuna SA. Etiology of increased cancer incidence after solid organ transplantation. Transplant Rev. 2018;32(4):218-24. https://doi.org/10.1016/j.trre.2018.07.001
Bhat M, Mara K, Dierkhising R, Watt KDS. Immunosuppression, race, and donor-related risk factors affect de novo cancer incidence across solid organ transplant recipients. Mayo Clin Proc. 2018;93(9):1236-46. https://doi.org/10.1016/j.mayocp.2018.04.025
Opelz G, Döhler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4(2):222-30. https://doi.org/10.1046/j.1600-6143.2003.00325.x
Eminger LA, Hall LD, Hesterman KS, Heymann WR. Epstein-Barr virus: dermatologic associations and implications: part II. Associated lymphoproliferative disorders and solid tumors. J Am Acad Dermatol. 2015;72(1):21-34. https://doi.org/10.1016/j.jaad.2014.07.035
Opelz G, Unterrainer C, Süsal C, Döhler B. Efficacy and safety of antibody induction therapy in the current era of kidney transplantation. Nephrol Dial Transplant. 2016;31(10):1730-8. https://doi.org/10.1093/ndt/gfw086
Finalet Ferreiro J, Morscio J, Dierickx D, Vandenberghe P, Gheysens O, Verhoef G, et al. EBV-positive and EBV-negative posttransplant diffuse large B cell lymphomas have distinct genomic and transcriptomic features. Am J Transplant. 2016;16(2):414-25. https://doi.org/10.1111/ajt.13558
Kumar D, Patil N, Husain S, Chaparro C, Bhat M, Kim SJ, et al. Clinical and virologic outcomes in high-risk adult Epstein-Barr virus mismatched organ transplant recipients. Clin Transplant. 2017;31(7). https://doi.org/10.1111/ctr.13000
Hernández-Sierra A, Rovira J, Petit A, Moya-Rull D, Mazuecos MA, Sánchez-Fructuoso AI, et al. Role of HHV-8 and mTOR pathway in post-transplant Kaposi sarcoma staging. Transpl Int. 2016;29(9):1008-16. https://doi.org/10.1111/tri.12800
Lebbé C, Legendre C, Francès C. Kaposi sarcoma in transplantation. Transplant Rev. 2008;22(4):252-61. https://doi.org/10.1016/j.trre.2008.05.004
Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, et al. Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell. 2003;3(1):23-36. https://doi.org/10.1016/s1535-6108(02)00237-4
Desai R, Collett D, Watson CJE, Johnson PJ, Moss P, Neuberger J. Impact of cytomegalovirus on long-term mortality and cancer risk after organ transplantation. Transplantation. 2015;99(9):1989-94. https://doi.org/10.1097/tp.0000000000000641
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