Solid Organ Transplants From Deceased Donors With Primary Brain Tumors

Recipients of solid organ transplants face a small risk of disease transmission from donor to recipient, and active malignancy is usually a contraindication to organ donation. However, because primary brain tumors rarely spread beyond the central nervous system, the use of organs from patients with primary brain tumors is generally accepted.

According to George H. B. Greenhall, MBChB, and colleagues, there are varying opinions regarding the safety of organ transplants from donors with brain tumors. International guidelines reflect this uncertainty, with wide variation in risk stratification, and guidelines in the United States are notably more conservative than in Europe.

The researchers conducted a cohort study in England and Scotland to determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. The researchers also sought to examine the association between brain tumors and organ usage and posttransplant survival. Results of the study were reported in JAMA Surgery [2023;158(5):504-513].

The study was conducted from January 1, 2000, to December 31, 2016; follow-up continued to December 31, 2020. The researchers utilized 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 Services (England), and the Scottish Cancer Registry. In secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure.

The study exposure was a history of primary brain tumor in the organ donor, identified from all three data sources using disease codes. The primary outcome of interest was transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes included organ utilization, and survival of kidney, liver, heart, and lung transplants and their recipients. Tumor grade and treatment history in donors with brain tumors were key covariates.

The study population included 13,274 solid organ donors. Of those, 2% (n=282) had primary brain tumors. Median age of the cohort with a primary brain tumor was 42 years, 55% (n=154) were female, and 45% (n=128) were male. Compared with donors without brain tumors, those in the brain tumor cohort were younger, had fewer comorbidities (eg, hypertension [15%, 42/282 vs 25%, 3230/12,992]) and lifestyle risk factors (eg, smoking [24%, 69/282 vs 46%, 5970/12,991]). Donors with brain tumors also had more favorable organ risk markers (median terminal creatinine, 65 µmol/L vs 75 µmol/L). Median time from brain tumor diagnosis to death was 8 days. Of the 282 tumors, 74% (n=210) had a histological diagnosis, and 8% (n=22) were confirmed on biopsy at the time of organ retrieval.

There were a total of 887 transplants utilizing 1014 organs donated from the 282 donors with primary brain tumors. Of those, 88% (n=778) were included in the analysis for the primary study outcome. There were 262 transplants from donors with high-grade brain tumors, including 81 from donors with grade 3 tumors and 142 from donors with grade 4 tumors. Sixty-three percent of transplants (n=490) were from donors with prior neurosurgical intervention or radiotherapy. Donors defined as high risk by Organ Procurement and Transplantation Network (OPTN) guidelines generated 605 transplants, including 60 transplants from donors with glioblastoma and no history of neurosurgery or radiotherapy which may be considered as intermediate risk by OPTN criteria.

Median age of recipients of transplants from donors with brain tumors was 48 years, and 61% (n=476) were male. Recipient characteristics of recipients of transplants from brain tumors were similar to recipients of transplants from donors without brain tumors.

Over a median follow-up of 6 years, there were 83 posttransplant malignancies (excluding nonmelanoma skin cancer) in 79 recipients of transplants from donors with brain tumors. Of 45 tumors in recipients of kidney transplant, 33% (n=15) were reported to National Health Services Blood and Transplant. No recipient tumors had a histological type matching that of the donor brain tumor. There were four tumors in kidney recipients with unspecified primary site or histology, occurring between 4 and 14 years following transplant; expert review concluded that cancer transmission was highly unlikely in those cases. In all other cases, transmission of donor brain tumor was excluded.

The 10-year survival of transplants from donors with brain tumors was 65% (95% CI, 59%-71%) for single kidney transplants, 69% (95% CI, 60%-76%) for liver transplants, 73% (95% CI, 59%-83%) for heart transplants, and 46% (95% CI, 29%-61%) for lung transplants. Nine transplants from donors with brain tumors (6 kidney, 2 liver, 1 heart) were excluded from the matched survival analysis due to lack of follow-up data (n=2), incomplete matching variables (n=4), or no available matches (n=3). Compared with matched controls, there was no evidence of a difference in transplant survival. Results were similar in separate analysis of patient and graft survival.

The researchers cited some limitations to the study findings, including the inability to incorporate data from the Welsh and Northern Ireland cancer registries, and the possibility that the risk stratification of the tumors in the study may be oversimplified.

In conclusion, the authors said, “This cohort study has three principal findings. First, results suggest that the risk of cancer transmission from donors with primary brain tumors was lower than that previously thought. No transmission occurred despite many donors having high-grade tumors or undergoing prior surgical intervention, both of which are considered as increasing the risk of transmission. Second, results suggest that donors with brain tumors were a source of good-quality organs, as evidenced by favorable risk markers and excellent transplant outcomes. Third, there may have been an aversion by transplant clinicians or their patients to use some organs from donors with high-grade brain tumors. The variation in utilization between organs may reflect differences in risk tolerance, although it is interesting that the rate of lung utilization was so low, considering the high mortality of patients on the waiting list for lung transplants.

“Taken together, these observations suggest that it may be possible to expand organ usage from donors with primary brain tumors without negatively impacting outcomes. Although this is likely to result in a modest increase in the number of transplants in the United Kingdom, our findings may be particularly relevant to counties with more conservative guidelines, including the United States. Our findings should help transplant clinicians when discussing the risks and benefits of accepting an organ offer. Analysis of pooled data could help to refine risk estimates in this area.”

Takeaway Points

1. Researchers reported results of a study examining the risk of cancer transmission associated with solid organ transplants from donors with primary brain tumors.
2. Despite many donors having high-risk tumors or undergoing prior surgical interventions, there were no cancer transmissions from donor to recipient.
3. As shown by favorable risk markers and good transplant outcomes, deceased donors with primary brain tumors were a source of good-quality organs in this study cohort.

Source: JAMA Surgery