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Clinical and Translational Research

Cancer Transmission From Organ Donors—Unavoidable But Low Risk

Desai, Rajeev1,5; Collett, Dave1; Watson, Christopher J.2; Johnson, Philip3; Evans, Tim4; Neuberger, James1

Author Information
doi: 10.1097/TP.0b013e318272df41
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Transmission of cancer from organ donor to recipient is a well-recognized complication of transplantation (1). Cancer transmission has been reported from donors with (2–7) and without a history of cancer (8–12). The most recent and largest transplantation registry report published 10 years ago estimated that the risk of cancer transmission was 0.01% (13). This study included all donors regardless of whether they had a history of cancer. The risk of tumor transmission from a donor with a history of a specific cancer is not known. Since this report, the risk profile of the donors has changed with increasing donor age and higher proportion of donation after circulatory death (DCD) donors (14).

The published literature regarding cancer transmission from donors primarily includes case reports and small series and so does not allow an accurate estimation of this risk. The most extensive review of this literature was published by the Disease Transmission Advisory Committee of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) and included guidelines for stratification of transmission risk for donors with known cancer (15). The NOTIFY project is the initiative of the World Health Organization (WHO) addressing this issue, in collaboration with the Italian National Transplant Centre. This project also highlighted different levels of confidence about the donor origin of the transmitted cancer (proven, probable, possible, unlikely, or intervention undertaken without documented transmission) based on the heterogeneity of data (16).

Isolated cases of donor-transmitted cancers (DTCs) reported from recipients from the United Kingdom include melanoma, colon cancer, and lung cancer (9, 11, 17). Here, we report the results of the first comprehensive national survey of all transplantation centers in the United Kingdom to establish the extent of DTC and donor-derived cancer [DDC], donor characteristics, circumstances of cancer transmission, recipient management, and outcome. This assessment of the risk of cancer transmission is vital for obtaining informed consent from prospective recipients and has clinical and medicolegal implications.


A total of 30,765 solid organ transplantations performed between January 1, 2001, and December 31, 2010, were included. The kidney recipient group included recipients of kidney only (n=19,784); kidney and pancreas (n=1112); kidney and liver (n=119); kidney and heart (n=12); and kidney, liver, and pancreas (n=2). The liver recipient group included recipients of liver only (n=6612), liver and pancreas with or without intestine (n=28), liver and heart (n=2), and liver and lung (n=3). The lung recipient group included recipients of lungs only (n=1257) and heart and lung recipients (n=110).

Donor origin cancers (DOCs) were identified in 18 recipients (18/30,765 [0.06%]; Table 1). Of these, three cases were likely DDC (0.01%). One was a transitional cell carcinoma occurring in the recipient of a kidney from a live donor, diagnosed 23 months after transplantation. This is likely to be a DDC because of interval from transplantation; the donor remains free from cancer 50 months after donation. The second case was of a renal cell cancer found incidentally in a kidney explanted for benign disease. This was likely a DDC because the tumor was small (not seen on cross-sectional imaging) and was found 38 months after transplantation. The third case was a lymphoma of (suspected) donor origin presenting as a mass in the hilum of the transplanted liver 5 months after transplantation. The deceased donor showed no evidence of lymphoma at donation.

Transplant activity in the United Kingdom and cases of DOC between 2001 and 2010

DTC is Rare but Unavoidable

Of 30,765 recipients, 15 (0.05%) developed DTC from 13 donors (Table 2). In none of the cases was the presence of cancer known at the time of transplantation. These donors had donated organs to 19 other recipients, none of whom showed evidence of cancer. Cancer was transmitted from one donor to multiple recipients on two occasions (lung cancer and lymphoma).

Cancer transmission and nontransmission from donor to recipients

Cancer Transmission is Associated With Donor Age

During the study period, 25,697 organs were transplanted from 14,986 donors. Organs from 13 donors, transmitted cancer giving a cancer transmission rate of 0.09% for donors (13/14,986) and 0.06% for organs transplanted (15/25,697). The cancer transmission rate was 0.14% for donation-after-brain-death donors (9/6559) and 0.24% for DCD donors (4/1653). There was no case of cancer transmission from living donors. We compared the donors who transmitted cancer against donors who did not (Table 3, unadjusted results). Multivariate analysis using logistic regression showed that the risk of cancer transmission was significantly associated with donor age 45 years or older (odds ratio [OR], 9; 95% confidence interval [CI], 1.2–69.6). None of the other variables tested showed a significant association with transmission of cancer after adjusting for all other factors—donor gender (OR, 2.2 for males; 95% CI, 0.7–7.3), smoking history (OR, 1.6 for smokers; 95% CI, 0.5–4.8), donor obesity (OR, 2.2; 95% CI, 0.6–7.3), donor type (OR, 1.9 for DCD relative to donation after brain death; 95% CI, 0.6–6.5).

Donor characteristics (unadjusted results)

Although it would have been helpful to assess transmission rates from donors with a past history of a specific cancer, because none of the donors whose donated organs resulted in transmission had a history of cancer at the time of transplantation, it was not possible to assess cancer-specific transmission rates.

Early DTC are Localized and Amenable to Surgery

Of 15 recipients, 11 (73%) developed early DTC (presenting within 6 weeks of transplantation) and were diagnosed at a median time from transplantation of 7 days (range, 0–39). Nine of these (six renal cell cancers and three lung cancers) were detected incidentally on histology and ultrasound scan performed for other reasons or in the explanted graft. In the remaining two cases (of lymphoma from the same donor), DTC was diagnosed on biopsies of the grafted kidneys performed after the identification of cancer during postmortem examination of the donor liver that looked macroscopically normal. None of the cases of early DTC showed evidence of spread of cancer outside the graft. Surgical treatment (explant/excision) was recommended to all recipients with early DTC (except for one recipient who had <1-mm renal cell cancer that could not be localized on cross-sectional imaging) and was accepted by eight recipients. The two recipients with donor-transmitted lymphoma both refused surgery and, after chemotherapy, were well and cancer free 12 months after transplantation.

Four recipients developed late DTC including lung cancer (two), neuroendocrine tumor (one), and colon cancer (one) diagnosed after a median duration of 318 days (range, 192–849). In three of these cases, the cancer had metastasized outside the graft at the time of diagnosis.

DTC has an Adverse Effect on Recipient Outcome and Outcome is Worse With Late DTC

Of 15 recipients, 3 (20%) with DTC died as a direct consequence of cancer, and all 3 developed late DTC. Out of seven kidney recipients undergoing explantation, six returned to long-term dialysis. Five-year survival of kidney recipients was lower in recipients with transmitted cancer as compared with recipients without transmitted cancer (83% and 93%, respectively), and this difference approached but did not reach statistical significance (P=0.077). Kidney recipients with DTC had more risk of death within 5 years of transplantation compared with recipients without DTC, but this difference was not statistically significant (P=0.116) after adjusting for age and gender (hazard ratio, 3; 95% CI, 0.8–12.1).


Clinical Implications

The incidence of DTC in our series (0.05%) is higher than the rate of 0.01% reported by the OPTN/UNOS (13). This study analyzed 108,062 recipients from 34,933 donors for a period of 51 months and reported 15 cases of DTC. There was only one case of transmitted renal cell cancer, which was diagnosed 37 months after transplantation. In contrast, we found six cases of transmitted renal cell cancer, diagnosed at a mean duration of 4 days after transplantation (7% of all DTC compared with 38% in our series). However, a more recent report (18) from OPTN/UNOS indicates that, of 20 DTCs, 7 (35%) were renal cell cancers. In our study, all six cases of renal cell cancer were identified as incidental findings on biopsies performed routinely at the time of transplantation or to assess early graft dysfunction. There were two cases of transmitted lung cancer in the earlier OPTN/UNOS cohort compared with the five cases in our cohort (13% of all DTCs compared with 33% in our series). Two of the transmitted lung cancers in our cohort were identified on routine biopsies performed at transplantation. The reasons for these differences may include different periods, differing donor profiles, and variations in reporting and in indications for biopsy.

Although many countries have efficient and large national transplantation registries, the number of DTC cases remains small, and this highlights the importance of global initiatives, such as the NOTIFY project led by WHO and the Italian National Transplant Centre, in helping understand the extent of the problem. Data collated from several countries are more likely to increase the robustness of the study and the power of statistical analysis. However, the limitations of such multinational projects would include the different demography of donors and recipients, varying inclusion/exclusion criteria for donors with known cancer, and genetic differences that may result in heterogeneity in the types of cancers and their biologic behavior.

Reducing the Risk of Cancer Transmission

All donors undergo assessment to detect transmissible diseases before organ donation. This includes history; examination; chest x-ray; blood tests; and enquiry with family, close friends, and primary care physician. In the United Kingdom, cross-sectional imaging and tumor markers are not routinely requested before donation, but reports are reviewed, if available. A history of recent or active cancer in the donor usually results in exclusion from transplantation. Exceptions to this are localized nonmelanoma skin cancers and selected cancers of the central nervous system, which have low risk of transmission. In our series, at the time of transplantation, none of the donors whose organs transmitted cancer was known to have past or active cancer highlighting the difficulty in eliminating the risk of cancer transmission completely.

In the United Kingdom, donor age is increasing (14). In 2010 to 2011, 53% of the donors were aged 50 years or older as compared with 42% in 2001 to 2002. With increasing proportion of older donors, the likelihood of occult cancer in the donor is likely to increase, resulting in increased chances of cancer transmission to the recipients. There have been cases of transmitted cancer in the United Kingdom before our study period, such as the case of transmitted melanoma (17), and such cases continue to be diagnosed since this report was completed.

Management of Recipients With Transmitted Cancers

Based on these observations and those in the literature, it is possible to make some tentative recommendations. However, wider discussion is needed before these observations can be translated into formal guidelines.

Before Transplantation

All potential transplantation candidates should be counseled about the benefits and risks of transplantation in line with current practice. Informed consent should include information about the risk of cancer transmission. As shown in our study with an incidence of 0.05% and cancer-related deaths in 20% of recipients developing DTC, it is important to highlight the rarity of transmission and also the possible outcome when such transmission does occur. Informed consent provides significant advantages in clinical management and also has medicolegal implications.

After Transplantation

Management of the recipient with transmitted cancer will be dependent on many factors, including the type and stage of cancer, organ transplanted, comorbidities, time after implantation, immunosuppression, and recipient’s wishes. As the number of recipients who developed transmitted cancer in our cohort was small and treatment varied, it is not possible to provide evidence-based guidelines. Graft explantation is likely to benefit kidney/pancreas recipients with transmitted cancer diagnosed in the early posttransplantation period and is likely to be most beneficial when there is no evidence of spread of cancer outside the graft. In the presence of metastatic disease, explantation should be discussed because the outcome from cancer is likely to improve after stopping immunosuppression as the tumor is rejected (19). However, the ability to be rejected may also be a reflection of the degree of tumor differentiation and expression of donor human leukocyte antigen; a very poorly differentiated tumor may not incite the same immunologic response by the recipient as a well-differentiated tumor. In transplants other than kidney/pancreas transplants, benefits of explantation should be weighed against the risks associated with retransplantation and the likelihood that the tumor has already spread beyond the graft. In cases where explantation is not an option, lowest possible immunosuppression should be used. Use of mammalian target of rapamycin inhibitor immunosuppression may be considered because it seems to be active against some tumors (20, 21).

Management of Recipients of Other Organs

When a recipient develops a transmitted cancer, recipients of other organs from this donor should be informed and investigated for cancer transmission. Accurate stratification of risk of cancer transmission to such recipients is difficult. This depends on the type, stage, and grade of cancer in the index recipient; tumor biology; and donor postmortem details, when available. It is notable in our series that transmission of cancer to multiple recipients was seen only when the donor cancer was a lymphoma or small cell lung cancer. Recipients with no evidence of cancer transmission should undergo cancer surveillance. Benefits of graft explantation in such situations should be assessed based on the details of the cancer in the index recipient.

Caveats of the Study

As with all such studies, the reported incidence of DTC is likely to be an underestimate. DTCs were identified retrospectively, and we included only those cases where donor origin was confirmed (or suspected, in one case). It is possible that, in some cases of cancers in the recipient, donor origin was not suspected or investigated, and some recipients may have died with transmitted cancer that was not identified. It is also possible that not all cases were reported, although we have worked exhaustively to mitigate these concerns and conclude that the risk of significant underestimation is very low.


The U.K. Transplant Registry was used to identify all recipients of solid organ transplant in the United Kingdom, between January 1, 2001, and December 31, 2010. Recipients who had developed DOC were identified by a combination of methods including database search at the transplantation centers, consultation with transplantation consultants and coordinators, and by searching through clinical governance reports held by the National Health Service (NHS) Blood and Transplant. Cancers in the recipients had been confirmed to be of donor origin using histology, molecular genetic techniques, or human leukocyte antigen analysis in all cases except for one case of donor-derived lymphoma (where the donor origin of cancer was suspected).

Classification of DOC as DDC and DTC is useful, but it can often be a challenge to distinguish the two. In comparison with DDC, DTC can be diagnosed with a high degree of confidence when the cancer is identified at the time of or soon after transplantation or in those cases where the donor is known to have the same type of cancer. The criteria for inclusion as DTC were:

  • - Cancers identified in the graft at the time of or within 6 weeks of transplantation
  • - Metastatic cancer deposit of donor origin identified in the graft (or elsewhere) any time after transplantation, without evidence of primary cancer (for example, colon cancer deposits in the liver graft with normal colonoscopy and normal colonic computed tomography)

Other DOCs were classified as DDC.

Cases of DTC were divided into early DTC (diagnosed within 6 weeks of transplantation) and late DTC (diagnosed after 6 weeks of transplantation).

Donors whose organs had resulted in cancer transmission were identified using the U.K. Transplant Registry and their characteristics (age, gender, type, smoking history, and body mass index [BMI]) were compared against the donors who did not transmit cancer, during the study period. Donors with unknown gender (n=20) were excluded. In donors older than 18 years, obesity was defined using the WHO definition (BMI≥30 kg/m2) (22). For donors between the ages of 5 and 18 years, WHO growth charts were used, and a BMI higher than the 95th percentile for age and gender was considered as obesity (23). Obesity rates for donors younger than 5 years were excluded from the analysis.

There are eight cancer registries in England, and these record all new cases of cancer. These have pooled their data to form the National Cancer Data Repository (NCDR), which contains data relating to cases of cancer registered by any one of the English registries. When a donation resulted in cancer transmission to one solid organ recipient, all other recipients of organs from this donor were identified using the U.K. Transplant Registry, and their details (NHS number, name, address, gender, date of birth, and date of death) were matched with those of the NCDR to establish if these donors and recipients were recorded to have cancer. Cancer data after 2008 and data for residents of Wales, Northern Ireland, and Scotland were not available in the NCDR. For these cases, data were obtained from the U.K. Transplant Registry and the transplantation centers.

For assessment of incidence, recipients who received a kidney with or without another solid organ were included in the kidney recipient group. Recipients of a liver with or without another solid organ (except kidney) were included in the liver recipient group. Combined heart and lung transplant recipients were included in the lung recipient group. Recipients of pancreas with or without intestine were included in the pancreas recipient group. Recipients registered with non-NHS transplantation centers (n=60) and recipients of intestinal transplant only (n=29) were excluded.

Unpaired t test without assuming equal variances was used to compare donor age and BMI between donors resulting and not resulting in cancer transmission. Donor characteristics and their association with cancer transmission were assessed using logistic regression. Differences in incidence rates of transmitted cancer between recipient groups were investigated using the Fisher exact test. Recipient survival was compared between recipients with and without DTC using the log-rank test. Hazard of death in recipients with and without DTC was compared using Cox regression. All calculations were performed using Statistical Analysis Software (SAS Institute, Cary, NC).


The authors thank the transplantation centers in United Kingdom for contributing to the data.


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Organ transplantation; Transmitted cancer; Donor assessment; Cancer transmission risk

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