MO986: Incidence And Predictors of Post-Transplant De-Novo Malignancy: A Single-Centre Retrospective Cohort Study
Authors: Austin Chukwu Chukwuma , Pullerits Kairi , Garland Shona , Middleton Rachel , Chinnadurai Rajkumar , A. Kalra Philip 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Improvement in short to medium term kidney transplant outcomes and increasingly successful transplantation older patients have led to increasing occurrence of long-term complications of transplantation. Amongst these complications, cancer has become an important cause of mortality following kidney transplantation necessitating the need to better understand the risk factors for the development of de novo malignancy.
This study aimed to evaluate the prevalence and the risk factors of de-novo malignancy in a single UK tertiary nephrology centre.

METHOD
This retrospective cohort study included all kidney transplant recipients (KTR) at our centre, that underwent kidney transplantation between 2000 and 2020 and followed up at our centre. The incidence and types of malignancies excluding non-melanoma skin cancer (NMSC) were analysed. The characteristics of KTR with post-transplant malignancy (excluding NMSC) were compared to those without post-transplant malignancy. Univariate and multivariate logistic regression analyses were conducted to identify the risk predictors of post-transplant cancers. Graft survival and dialysis free survival and death with functioning graft were assessed using Kaplan-Mayer analysis and Cox-regression.

RESULTS
We analysed the records of 962 KTR (mean age = 47 ± 15 years), followed-up over a median period of 16 years. About 365 (38%) were women, and 783(81%) were Caucasian. 268(32%) had a pre-emptive transplant and 277(29%) had a live donor transplant.
Post-transplant malignancy was diagnosed in 84(9%) KTR. KTR with post-transplant cancers were likely to be older (53 ± 14 versus 47 ± 15 years; P = 0.004), on long-term steroid maintenance therapy (64% versus 47%; P = 0.004) and have a history of post-transplant DNA virus infection (40% versus 29%; P = 0.029). Conversely, those with cancers are less likely to be on mycophenolic acid (MPA) therapy (65% versus 78%; P = 0.023). The most common cancers diagnosed were genitourinary cancers (27%) followed by gastrointestinal (24%) and haematological cancers (24%). Respiratory, neurological and others accounted for 10%, 2.4% and 11% of the diagnosed cancers.
In multivariate logistic regression analysis, increasing risk of post-transplant cancer was associated with older age at transplantation [OR: 1.81 (1.3–2.5; P &lt; 0.001)], male gender [OR 2.3 (1.3–8.3; P = 0.01)], corticosteroid maintenance [OR 2.3 (1.1–5.2: P = 0.03)], Tobacco smoking [OR: 3.33 (1.2–8.9: P = 0.01)], higher Baseline estimated glomerular filtration rate (eGFR), [OR: 1.2 (1.0–1.4; P = 0.02)], and post-transplant DNA-virus infection [OR: 2.3 (1.0–5.1; P = 0.02)] (Figure 1).
There was no difference in the death censored graft survival between the cancer group and the no-cancer group (log-rank, P = 0.51). However, those with cancers had a significantly worse dialysis free survival (log-rank; P = 0.04) and significantly higher death with functioning graft (log-rank; P = 0.02). In the multivariate Cox regression, adjusted for several confounders, dialysis free survival did not differ significantly between the cancer and non-cancer groups (adjusted hazard ratio; aHR: 1.6; P = 0.10). However, age (aHR: 1.16; P = 0.01), male gender (aHR: 1.6; P = 0.01), cardiovascular disease (CVD) (HR: 1.6; P = 0.01) and acute rejection (aHR: 1.7; P = 0.02) were predictors of lower dialysis free survival.

CONCLUSION
Post-transplant cancers occurred in 9% of our cohort during a median follow-up of 16years. Genitourinary cancers were the most commonly occurring cancers. Older age, male gender, corticosteroid maintenance, smoking and DNA virus infections were the risk factors of malignancy. There was no significant difference in dialysis free survival between the cancer group and the no cancer groups. Lower dialysis free survival was predicted by age, gender, CVD and a history of acute rejection.