De novo sarcomas in solid organ transplant recipients.
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Adolescent↗
Biomedical subjects
M J Hanaway
Publications and source records attributed to M J Hanaway.
Polyomavirus in kidney and kidney-pancreas transplantation: a defined protocol for immunosuppression reduction and histologic monitoring.
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Biopsy↗
Transmission of donor cancer into cardiothoracic transplant recipients.
BACKGROUND: The demand for transplantable organs exceeds donor supply. Patients with central nervous system (CNS) or other tumors are controversial donors, and the donor cancer transmission rates in cardiothoracic transplant recipients have not been determined. The Israel Penn International Transplant Tumor Registry (IPITTR) was queried to define the risk of donor cancer transmission in cardiothoracic transplant recipients. METHODS: All heart, lung, or heart-lung recipients of organs from donors with a history of malignancy were reviewed. Donor and recipient demographics, histologic findings, and recurrence were reviewed. RESULTS: Twenty-two patients received 17 hearts, 3 lungs, and 2 heart-lung transplants from donors with known CNS or other malignancies. No malignancy transmissions were noted with astrocytomas (n = 3) or glioblastomas (n = 1), except a medulloblastoma that recurred at 6 months. The transmission rate for CNS tumors was 17% (1 of 6), and 1- and 3-year survivals were 67% and 50%, respectively. The most common non-CNS donor cancer was renal cell carcinoma (n = 5). Two renal cell cancer transmissions occurred, both when vascular extension was present. The most aggressive tumor transmission was choriocarcinoma (n = 2) and melanoma (n = 2). Two of 3 choriocarcinomas metastasized with 67% mortality, and both melanomas were transmitted and resulted in death. Other donor cancers included angiosarcoma (n = 2), cervical (n = 1), lung (n = 1), prostate (n = 1), and a liver adenocarcinoma. The transmission rate for all non-CNS groups was 56% (9 of 16) with a 2-year survival of 40%. CONCLUSIONS: The IPITTR experience indicates that tumor transmission is high (10 of 22, 45%) in cardiothoracic transplant recipients. Similar to intra-abdominal organ recipients in the IPITTR, (1) renal cell carcinomas without capsular invasion appear safe with no transmission, (2) vascular invasion in renal cell carcinoma appears to result in early tumor transmission, and (3) melanoma and choriocarcinoma have high rates of transmission with early and almost universal death.
Brain Neoplasms↗
The role of anti-Galalpha1-3Gal antibodies in acute vascular rejection and accommodation of xenografts.
BACKGROUND: A major impediment to the transplanting of porcine organs into humans is the susceptibility of porcine organs to acute vascular rejection, which can destroy a vascularized xenograft over a period of hours to days. Acute vascular rejection of porcine-to-primate xenografts is thought to be triggered by binding of xenoreactive antibodies to the graft. We tested whether antibodies, binding to Galalpha1-3Gal epitopes in porcine tissue, initiate this phenomenon. METHODS AND RESULTS: Specific depletion of anti-Galalpha1-3Gal antibodies from the blood of baboons, using extracorporeal perfusion of separated plasma through columns of Sepharose beads covalently linked to the antigenic trisaccharide, Galalpha1-3Galbeta1-4GlcAc, averted the development of acute vascular rejection in porcine organs transgenic for human decay-accelerating factor and CD59. More importantly, after immunodepletion was stopped and Gala1-3Gal antibodies were allowed to return, these same organs continued to function and remained pathologically normal and thus seemed to achieve a state of accommodation. CONCLUSION: These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.
Acute Disease↗
Long-term results of liver transplantation in older patients 60 years of age and older.
BACKGROUND: Advances in perioperative care and immunosuppression have enabled clinicians to broaden the indications for organ transplantation. Advanced age is no longer considered a contraindication to transplantation at most centers. Although short-term studies of elderly liver transplant recipients have demonstrated that the incidence of complications and overall patient survival are similar to those of younger adults, transplant center-specific, long-term data are not available. METHODS: From August of 1984 to September of 1997, 91 patients 60 years of age or older received primary liver transplants at the University of Wisconsin, Madison. This group of patients was compared with a group of younger adults (n=387) ranging in age from 18 to 59 years who received primary liver transplants during the same period. The most common indications for transplantation in both groups were Laennec's cirrhosis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, and cryptogenic cirrhosis. There was no difference in the preoperative severity of illness between the groups. Results. The length of hospitalization was the same for both groups, and there were no significant differences in the incidence of rejection, infection (surgical or opportunistic), repeat operation, readmission, or repeat transplantation between the groups. The only significant difference identified between the groups was long-term survival. Five-year patient survival was 52% in the older group and 75% in the younger group (P<0.05). Ten-year patient survival was 35% in the older group and 60% in the younger group (P<0.05). The most common cause of late mortality in elderly liver recipients was malignancy (35.0%), whereas most of the young adult deaths were the result of infectious complications (24.2%). CONCLUSION: Although older recipients at this center did as well as younger recipients in the early years after liver transplantation, long-term survival results were not as encouraging.
Aged↗
The promise of xenografting.
Advances in understanding the rejection of foreign tissues has renewed enthusiasm about the possibility of overcoming the present organ shortage by transplanting porcine kidneys into humans. Currently, three known forms of organ rejection stand as obstacles to xenotransplantation as a clinical reality--hyperacute rejection, acute vascular rejection, and cellular rejection. Progress in the knowledge of xenoreactive antibodies and of complement, along with new transgenic technologies, have enabled researchers to overcome hyperacute rejection in xenografts. The advances have brought into focus such issues as the ability of the porcine kidney to replace the physiologic functions of the human kidney and the risk associated with the potential transmission of infectious agents from animals to humans. Despite the remaining hurdles to clinical application of xenotransplantation, the rapid pace of research and emerging technologies would seem to make xenotransplantation a renal replacement therapy of great promise.
Animals↗
Split tolerance induced by immunotoxin in a rhesus kidney allograft model.
BACKGROUND: Renal allografts were performed in rhesus monkeys using FN18-CRM9, a potent immunotoxin capable of depleting T cells to less than 1% of baseline levels in blood and lymph nodes, as a preparative agent. We have recently reported that animals pretreated with FN18-CRM9 1 week before transplantation without further immunosuppression had prolonged graft survival time compared with control animals, and frequently became tolerant. METHODS: This report examines the alloimmune responses of recipient monkeys to the donor, including cytotoxic T lymphocyte precursor (CTLp) frequency, mixed lymphocyte response, and antidonor IgG response. RESULTS: CTLp frequencies declined significantly (P<0.01) after FN18-CRM9 treatment and renal transplantation. This decline in CTLp was initially nonspecific, as CTLp frequencies against third-party animals also declined (P<0.01). The decrease in CTLp was maintained in five of five animals tested 6 months after transplant. However, unresponsiveness was limited to the CTL arm of the immune response as antidonor IgG was detected in four of four animals tested, and the 5-day mixed lymphocyte response stimulation index and relative response were not significantly different before and after transplant. In long-term survivors (>150 days), an increase in anti-third-party CTLp was detected 1 month after grafting with third-party skin. No change was seen in the antidonor CTLp frequency after donor skin grafting, indicating that a specific defect in the antidonor CTL response had developed. CONCLUSIONS: These data suggest that FN18-CRM9 treatment of rhesus monkeys allows the development of specific down-regulation of antidonor CTL activity in renal allograft recipients.
Animals↗
FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts.
BACKGROUND: Transplant tolerance, rather than immunity, may be favored in the setting of a lower mature lymphoid mass in the recipient induced by anti-T cell agents. A novel immunosuppressive agent, FN18-CRM9, known to specifically kill T cells with great potency, was evaluated in a transplant model. METHODS: In order to ablate recipient T cells, the immunotoxin FN18-CRM9 was administered to rhesus monkey recipients of MHC-mismatched renal allografts. Donor lymphocytes were injected intrathymically into some animals. RESULTS: All monkeys with T-cell depletion by immunotoxin had prolonged allograft survival, and tolerance confirmed by skin grafting has been confirmed in five of six long-surviving recipients. CONCLUSIONS: In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance.
Animals↗
Immunosuppressive effects of an HLA class I-derived peptide in a rat cardiac allograft model.
B7.75-84, a 10-amino-acid peptide derived from the HLA-B7 molecule, prolongs rat heterotopic cardiac allograft survival time (GST) when used with cyclosporine in the Lewis-to-ACI strain combination. We evaluated the ability of B7.75-84 to prolong GST in other strain combinations without cyclosporine and studied the effect of B7.75-84 on the immune response in the Wistar-Furth (WF)-to-ACI strain combination. GST was markedly prolonged in most low-responder (ACI) recipients but only slightly prolonged in the high-responder (Lewis) recipient. Cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) limiting dilution assays (LDA) were performed 10 days after cardiac allografts from WF donors were placed in ACI recipients treated with B7.75-84. HTL-LDA assays at 10 days posttransplant showed a slight decrease in HTL precursor frequency and a decrease in their IL-2 production in B7.75-84 treated recipients with prolonged GST in response to donor antigen as well as third-party (Lewis) antigen. CTL-LDA assays at day 10 showed no difference in CTL precursor frequency among treated recipients but did show a significant decrease in CTL killing activity against donor cells in recipients with prolonged GST. No significant difference in CTL killing activity was seen against third- party cells. Antibody analysis was performed at day 8 in treated recipients. Serum from B7.75-84-treated recipients with prolonged graft survival generally showed no detectable IgG antibody response against donor MHC class I antigen. All B7.75-84 treated recipients showed a strong IgM response against donor antigen regardless of allograft outcome. Our results suggest that the immunosuppressive effect of B7.75-84 in rats is greater using a low-responder RT1 haplotype. Furthermore, B7.75-84 induces a nonspecific decrease in HTL function while producing a donor-specific decrease in CTL function and a diminished antidonor MHC class I IgG response.
Animals↗