Selection of Patients for Initial Clinical Trials of Solid Organ Xenotransplantation

Abstract

Several groups have reported extended survival of genetically-engineered pig organs in nonhuman primates, varying from almost 10 months for life-supporting kidney grafts and >2 years for nonlife-supporting heart grafts to less than 1 month for life-supporting liver and lung grafts. We have attempted to define groups of patients who may not have an option to wait for an allograft. These include kidney, heart, and lung candidates who are highly-allosensitized. In addition, some kidney candidates (who have previously lost at least 2 allografts from rapid recurrence of native kidney disease) have a high risk of further recurrence and will not be offered a repeat allotransplant. Patients with complex congenital heart disease, who may have undergone previous palliative surgical procedures, may be unsuitable for ventricular assist device implantation. Patients dying of fulminant hepatic failure, for whom no alternative therapy is available, may be candidates for a pig liver, even if only as a bridge until an allograft becomes available. When the results of pig organ xenotransplantation in nonhuman primates suggest a realistic potential for success of a pilot clinical trial, highly-selected patients should be offered participation.

Advances in the immunology of heart transplantation

“…Perhaps those with complex congenital heart disease, who may have undergone previous palliative surgical procedures and are unsuitable for ventricular assist device implantation. 84 …”

Liver xenotransplantation

“…As such, initial trials should focus on including those patients who are unable to wait and in whom no alternative therapy is available. (25) Clinically, these patients often have the one of the follow three clinical conditions: 1) ALF, 2) primary liver allograft failure due to primary non function or hepatic artery thrombosis within seven days of transplant, or 3) acute decompensation in the setting of chronic liver disease. (25) In these individuals who would otherwise die due to lack of organ availability, experimental application of LXT could serve as a bridge until an organ is available for allotransplantation.…”

“…(25) Clinically, these patients often have the one of the follow three clinical conditions: 1) ALF, 2) primary liver allograft failure due to primary non function or hepatic artery thrombosis within seven days of transplant, or 3) acute decompensation in the setting of chronic liver disease. (25) In these individuals who would otherwise die due to lack of organ availability, experimental application of LXT could serve as a bridge until an organ is available for allotransplantation. (25) Assuming success with these initial clinical trials assessing the safety and efficacy of orthotopic LXT, destination therapy can then ultimately be pursued.…”

Xenotransplantation

“…Rapid improvement in the results of preclinical studies has made the field more hopeful of the initiation of clinical trials [8–11]. Recent papers have discussed the selection of patients for initial clinical trials for solid organ xenotransplantation [12] and islet xenotransplantation. We here briefly review progress in pig-to-NHP models.…”