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Commentaries

Donors With Central Nervous System Cancer

Proceed With Vigilance

Nalesnik, Michael A. MD1

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doi: 10.1097/TP.0000000000002995
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In this issue of Transplantation, Lee et al1 document the absence of disease transmission among 87 transplant recipients who received organs from 28 brain-dead donors with central nervous system (CNS) tumors. Specific tumor pathology was available in the cases of 17 donors (51 recipients) and was unknown for the other 11 (36 recipients). Six were considered high-risk tumors by World Health Organization (WHO) histological classification (grade III or IV) and the other 11 low-grade (WHO I–II). They conclude that organ donation from donors with CNS tumors should be actively promoted because the risk of disease transmission is very low.

This study sends an important message for standardization about these potential donors in the Republic of Korea. The Korean Organ Transplant Act was enacted in 2000 to introduce transparency to the process of deceased donor organ allocation, and the Korean Network for Organ Sharing has had to overcome difficulties in its efforts to meet the medical need.2 In 2018, deceased donors accounted for only 16% of the 2854 donors who provided organs for 3907 transplants in the Republic of Korea.3

Korean transplant policy has strict criteria about potential donors with cancer but does allow transplantation in the case of “primary brain tumors not transmitted to other organs.” However, the lack of more refined criteria means that individual institutions are left to make arbitrary decisions about transplantation in this circumstance.

The study of Lee et al,1 although dealing with a relatively small number of patients, is well documented and their conclusion falls in line with other reports. In 1999, Chui et al4 documented an absence of tumor transmission among 96 recipients who received organs from donors with malignant CNS tumors. Three years later, Kauffman et al5 reported Organ Procurement and Transplantation Network/United Network of Organ Sharing data that showed no evidence of transmission among 1220 organs transplanted from donors with CNS tumors or histories of CNS tumors. Although, in most cases, the histological tumor types were unknown, 56 recipients received organs from donors with WHO grade IV tumors. In 2003, Buell et al6 called attention to potential risk factors for CNS tumor transmission based on features of cases reported to the Israel Penn International Tumor Registry. They found ventriculoperitoneal shunts, high-grade tumors, extensive craniotomies, and cerebellar lesions to represent individual risk factors. Transmission frequency was 7% in the absence of risk factors, 36% with 1 risk factor, and 43% with 2 risk factors. Importantly, they recognized that their event-based registry likely overestimated these frequencies and concluded that there was a real, but undefined, increase in tumor transmission in the presence of these factors. In 2010, Watson et al7 reported the results of transplants in the UK registry from donors with CNS tumors. No tumors were seen in 448 recipients of organs from donors with CNS tumors. In this case, 33 of the 179 donors had known WHO IV neoplasms and the study encouraged increased utilization of these donors with the caveat of balancing the risk of transmission against the likelihood of mortality on the waitlist. In a follow-up study, Warrens et al8 formalized the risks based on these data and concluded that the risk of extraneural metastases of primary WHO grade IV CNS tumors excepting lymphomas (which are contraindicated) was 2.2% with a 95% upper confidence limit of 6.4%. The risk of metastases for WHO grade III tumors had an upper 95% confidence limit between 1.5% and 6.4%, and other primary CNS neoplasms had an upper confidence limit of 1.5% for extraneural spread. Regarding iatrogenic risk factors, they estimated that the increased risk from CSF shunt was likely <1% and they found no increased risk of extraneural spread in the settings of prior surgery, chemotherapy, or radiotherapy.

Although recent studies show the same trend, low risk does not mean risk-free, and all reports contain unavoidable shortcomings. Many reported donor CNS tumors do not include pathological diagnoses. Because approximately 70% of CNS tumors are benign, the majority likely fall into this category. Benign tumors are often reported along with malignant tumors, which could serve to “dilute” the results. Because most series report few to no transmissions, this may be inconsequential but may give a false sense of security regarding the strength of the evidence. Reliance on registry data can also introduce error. Engels et al9 found that the US Scientific Registry of Transplant Recipients missed 17.8% (26/191) of deceased donors and 100% (5/5) of living donors with brain cancer when compared with cancer registries, and also noted that cancer registries missed a proportion of diagnoses recorded in the US Scientific Registry of Transplant Recipients. Thus, the reported risk frequencies and derivative statistics are convenient yardsticks, but we must remain cautious of their accuracy.

Lee et al1 also state that their 11 donors considered as low risk by WHO criteria would be considered high risk by the United Network for Organ Sharing Disease Transmission Advisory Committee guidelines10 on the basis of iatrogenic risk factors. However, those Disease Transmission Advisory Committee criteria, derived from the original Buell study,6 are meant to be applied to malignant tumors and not to benign tumors such as grade I meningiomas. Nevertheless, additional data since that 2011 study suggest that the risk categorization for many malignant CNS tumors might be lowered from high to intermediate grade and an update to this guidance is awaited.

To their credit, Lee et al1 clearly report their patients in a manner that allows incorporation into the larger database of cumulative experience and this will ultimately aid in expanding the donor organ supply. Until we have the magic test that can quickly tell us if a CNS tumor in a potential donor will undergo extraneural spread, this type of information, along with clinical judgment and the wishes of the informed patient, will continue to serve as the basis that will allow us to follow the timeless precept: primum non nocere.

REFERENCES

1. Lee M-S, Cho W-H, Ha J, et al. Safety of donation of brain-dead organ donors with central nervous system tumors: analysis of transplantation outcomes in Korea.Transplantation2019
2. Min SI, Ahn C, Han DJ, et al. To achieve national self-sufficiency: recent progresses in deceased donation in Korea.Transplantation201599765–770
3. International Registry in Organ Donation and Transplantation.2019Available at www.irodat.org. Accessed September 15, 2019
4. Chui AK, Herbertt K, Wang LS, et al. Risk of tumor transmission in transplantation from donors with primary brain tumors: an Australian and New Zealand registry report.Transplant Proc1999311266–1267
5. Kauffman HM, McBride MA, Cherikh WS, et al. Transplant tumor registry: donors with central nervous system tumors.Transplantation200273579–582
6. Buell JF, Trofe J, Sethuraman G, et al. Donors with central nervous system malignancies: are they truly safe?Transplantation200376340–343
7. Watson CJ, Roberts R, Wright KA, et al. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK registry data.Am J Transplant2010101437–1444
8. Warrens AN, Birch R, Collett D, et al; Advisory Committee on the Safety of Blood, Tissues and Organs, UKAdvising potential recipients on the use of organs from donors with primary central nervous system tumors.Transplantation201293348–353
9. Engels EA, Castenson D, Pfeiffer RM, et al. Cancers among US organ donors: a comparison of transplant and cancer registry diagnoses.Am J Transplant2014141376–1382
10. Nalesnik MA, Woodle ES, Dimaio JM, et al. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk.Am J Transplant2011111140–1147
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