Sequencing of a central nervous system tumor demonstrates cancer transmission in an organ transplant

Gingras, Marie‐Claude; Sabo, Aniko; Cardenas, Maria F.; Rana, Abbas; Dhingra, Sadhna; Meng, Qingchang; Hu, Jianhong; Doddapaneni, Harshavardhan; Perez, Lesette; Korchina, Viktoriya; Nessner, Caitlin; Liu, Xiuping; Chao, Hsu; Goss, John A.; Gibbs, Richard A.

doi:10.26508/lsa.202000941

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…Although there were some recipient tumors with uncertain histology, raising the possibility of transmission, the knowledge that most donor-transmitted malignancies manifest within 2 years posttransplant makes transmission in these cases (which occurred several years after transplant) extremely unlikely . Ultimately, confirmation of tumor origin requires genetic analysis, which was beyond the scope of this study . Therefore, we cannot exclude cancer transmission with complete certainty.…”

Section: Discussionmentioning

confidence: 94%

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Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission

et al. 2023

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ImportanceCancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved.ObjectiveTo determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival.Design, Setting, and ParticipantsThis was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022.ExposuresA history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes.Main Outcomes and MeasuresTransmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history.ResultsThis study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls.Conclusions and RelevanceResults of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.

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Section: Discussionmentioning

confidence: 94%

“…65,66 Ultimately, confirmation of tumor origin requires genetic analysis, which was beyond the scope of this study. 67,68 Therefore, we cannot exclude cancer transmission with complete certainty. We also acknowledge that the risk stratification of the tumors in our study may be oversimplified.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission

et al. 2023

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Malignancy following solid organ transplantation: Current techniques for determination of donor versus recipient origin

Rojansky,

Marboe,

Berry

2024

Transplant Infectious Dis

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Among the post‐transplantation complications that patients may encounter, the transmission of a donor‐derived malignant neoplasm is uncommon but potentially life threatening. The determination of donor versus recipient origin is essential particularly in the setting of multiple transplant recipients from the donor. Advances in molecular biology now allow accurate discrimination utilizing routine tissue samples in a timely and cost‐effective manner. The techniques are routinely performed in hospital molecular biology laboratories and are also available in commercial labs. The current methodologies are discussed and future possibilities are presented for clinicians caring for solid organ recipients.

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The burden of medical contraindications to corneal donation: Time for review

Dorado-Cortez,

Poinard,

Epinat

et al. 2024

PLOS Glob Public Health

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Corneal graft (keratoplasty) is the most common allograft in the world, but the imbalance between the number of donors and the number of patients waiting for transplants is abysmal on a global scale and varies enormously from one country to another. The risk of transmission of systemic diseases from donor to recipient is demonstrably low. In over 50 years and an estimated 2.5 million transplants, only 8 cases of rabies, 2 cases of hepatitis B and 2 cases of Creutzfeldt-Jakob disease (CJD) have been documented. Conversely, other cases of rabies, HIV, hep C, hep B and CJD have not been transmitted via keratoplasty. The list of medical contraindications (CI) to corneal donation also includes diseases for which no actual, only theoretical, risk has been identified, in particular, neurodegenerative diseases, hematological malignancies, melanomas, tumors of the central nervous system, neoplastic meningitis and lymphangitic carcinomatosis. Their contribution to the reduction in the potential donor pool has not previously been investigated. We analyzed 45 months of exhaustive data from the hospital coordination for organ and tissue procurement at St-Etienne University Hospital (01/01/2020 to 06/09/2023). Out of the 2349 consecutive potential donors’ files analyzed by the coordination team,1346 (57%) had an CI to donation. The identification of a neurodegenerative disease was the most frequent, accounting for 16% of the files examined and 29% of CIs. Of these, 75% were related to cognitive disorders. The 5 diseases or families of diseases for which there is only theoretical risk of transmission equated to a loss of 712 potential donors, corresponding to 30% of the files examined and 53% of all CIs. Of the 1003 deceased without CI, 738 families (74%) were contacted. No objection to donation was received in 52% of cases, enabling 385 procurements to be carried out. Removing these 5 CIs would have increased the number of donors by 71% (658 instead of 385). The potential pool of corneal donors is significantly restricted by a group of CIs introduced decades ago in response to a theoretical transmission of disease. A substantive amount of evidence now suggests that many CIs now need to be reviewed, modified or discarded altogether. This approach will result in a highly significant worldwide increase in the availability of corneas for transplant and have an immediate and major impact in reducing corneal blindness across the globe. We propose that this reduction in CIs be accompanied by a prospective evaluation process, by allocating the corneas of these donors to patients aged 75 years and over, and by monitoring them for a minimum of 5 years.

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Sequencing of a central nervous system tumor demonstrates cancer transmission in an organ transplant

Cited by 3 publications

References 43 publications

Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission

Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission

Malignancy following solid organ transplantation: Current techniques for determination of donor versus recipient origin

The burden of medical contraindications to corneal donation: Time for review

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