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Transmission of donor diseases: efforts to protect recipients and increase deceased donor organ transplants.

The shortage of transplantable organs has prompted the possible use of donors with certain diseases – usually neoplastic or infections – that were previously eliminated because of the risk of disease transmission to the recipient. The Editors of Transplantation are pleased to present this journal supplement devoted to analysis of the risk of disease transmission from deceased donors in large European national organ transplant networks. These papers represent the proceedings of a symposium on the risk of cancer transmission after solid organ transplantation held in Rome in June 2007. Alessandro Nanni Costa of the Italian National Transplant Center (CNT) and colleagues note that the organ shortage has caused increased use of older donors with consequent increased risk of transmission of donor diseases. The CNT created an expert commission to define guidelines for evaluation of organ donors to develop methods for identification of risk factors and to create an expert task force to provide evaluation and second opinions of difficult cases. The guidelines describe five risk categories (unacceptable risk, increased but acceptable risk, calculated risk, not assessable risk, and standard risk) and enumerate specific details of medical history, physical examination, laboratory tests, and pathology examinations used to determine specific risk categories. They assign standard risk to donors with low grade tumors (nonmelanotic skin tumors, carcinoma in situ of the cervix and vocal cords, uroepithelial non-invasive papillary carcinoma, low grade prostate cancer, encapsulated papillary thyroid cancer, minimally invasive thyroid follicular cell carcinoma, and low grade renal cell cancer). They suggest donors with tumors with higher risks for transmission could be used if the potential benefit from the organ transplant is higher than risk of tumor transmission after expert second opinion and informed consent from the patient and/or family. Since institution of the guidelines and second opinion program (September 2003 through June 2007) 9519 potential deceased donors were identified in Italy of which 1611 presented a neoplastic (674) or infectious risk (937); 457 of 674 donors with neoplastic risks were excluded for absolute contraindications while 213 were designated as standard risk or increased but acceptable risk and provided 380 organs for transplantation. Potential donors increased from 1892 in 2003 to 2107 in 2006 ( 11.36%), while neoplastic risk donors increased from 109 to 152 ( 39.44%). Identification of donor neoplasia before and during organ retrieval dramatically increased while that after transplantation has decreased and no posttransplant neoplasms have been detected since 2006. Seventy-four of 937 infection affected donors were categorically excluded while 843 were classified as calculated risks donors and utilized for transplantation. Over 2000 organs from donors with infectious risk factors were transplanted. The authors emphasize that use of specific guidelines and the expert second opinion program in analysis of disease transmission risk was a major factor in permitting maximum utilization of calculated risk donors. Grigioni and colleagues from the University of Bologna and CNT report results of an earlier Italian Multidonor Cancer Screening Protocol utilized in 2002 through 2005 (later modified by the CNT to the protocol described above). Donors were categorized for neoplastic disease transmission risk as standard risk (no transmission risk), non-standard risk (low transmission risk with use restricted to certain clinical situations), and unacceptable risk (unconditional exclusion). This protocol was applied to 7608 deceased donor candidates in the three major Italian transplant networks. Clinical suspicion of cancer was raised for 337 (4.6%) donors of which 198 (2.6%) were designated with unacceptable risk for tumor transmission after pathological examinations. Eighty (1%) were included in the standard risk category and the remainder (59) considered as non-standard risks; together these donors provided a total of 241 organs in 231 recipients. All recipients transplanted with organs from non-standard risk donors have been carefully followed and no donor-recipient tumor transmission has thus far been identified. Garrido and Matesanz from the Spanish National Transplant Organization (ONT) present an interesting analysis of the ONT Tumor Registry. They note that of 20,016 donors in the ONT from 1990 to 2006, 117 donors had some type of malignant tumor (5.8 per 1000 donors) and 155 recipients received organs from these donors. The source of the tumor was kidney (55), central nervous system (32), prostate (5), and other sites (25). Donors with tumors were significantly older than those without tumors and their cause of death was more frequently of cerebrovascular etiology. The status of 100 of these 155 recipients is known; 22 (22%) are dead but in only 7 of 22 was death cancer related. Only 13 of the 100 recipients followed developed a malignant tumor of which 10 of the 13 were donor related. These data would suggest the chances of tumor transmission from uncategorized donors with known malignant tumors would be in the 6 to 10 per cent range. Investigators from the University of Pittsburgh present two papers with implications for cancer etiology in the setting of immunosuppression. Taioli and colleagues analyzed predictors of survival after lung transplant in a large single center cohort of 990 patients. They found that overall survival was 41.6% and that females tended to live longer than males with male risk of dying being 1.18 (95% CI 1.01–1.40) relative to females. Females who had at least one full term pregnancy had better survival rates than females who had no full term pregnancies. They hypothesized a hormonal contribution to enhanced survival possibly by development of some type of immunotolerance after pregnancy. They also suggested that this concept would be useful for understanding the role of immunity in cancer. Studer and colleagues present a discussion of the use of new molecular tools such as gene expression microassays as biomarkers for diagnosis and prognosis in The authors declare no potential conflicts of interest. Copyright © 2008 by Lippincott Williams & Wilkins ISSN 0041-1337/08/8508S-49 DOI: 10.1097/01.tp.0000312673.26520.5d