TLI + ATG for Liver Transplantation

(TEMPO-LT Trial)

This trial tests a new approach for individuals who have undergone a liver transplant, aiming to reduce or eliminate the need for lifelong immune-suppressing drugs. It combines two treatments: Anti-Thymocyte Globulin (ATG), an immune-suppressing drug, and Total Lymphoid Irradiation (TLI), a type of radiation therapy. These treatments help the body accept the new liver without rejection. The trial includes two groups: one receives the treatments immediately after surgery, while the other receives them later. It suits those undergoing a liver transplant at Stanford University who have no contraindications to these treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Research has shown that Anti-Thymocyte Globulin (ATG) is generally well tolerated by liver transplant patients, with studies indicating that serious side effects are rare. One study found that ATG significantly reduced the rate of organ rejection in transplant patients, with some experiencing a decrease from 31.8% to 14.5%.

However, ATG carries a higher risk of bacterial infections, with reports indicating about a 50% rate. Despite this, ATG is linked to lower mortality rates in liver transplant patients.

Regarding Total Lymphoid Irradiation (TLI), specific data is limited. It has been used safely in kidney transplants to reduce the need for immune suppression drugs, suggesting potential safety for liver transplants as well.

Researchers are excited about using Anti-Thymocyte Globulin (ATG) combined with Total Lymphoid Irradiation (TLI) for liver transplantation because it offers a novel way to induce immune tolerance. Unlike standard treatments that often rely on long-term immunosuppressive drugs to prevent organ rejection, this approach aims to improve graft engraftment by conditioning the immune system right after the transplant. This could potentially reduce the need for lifelong immunosuppression, minimizing side effects and improving the quality of life for transplant recipients. Additionally, the two treatment arms—synchronous and delayed tolerance—allow researchers to explore the timing of this conditioning regimen, which could lead to more personalized and effective transplant care.

This trial will evaluate the use of Anti-Thymocyte Globulin (ATG) and Total Lymphoid Irradiation (TLI) in liver transplants. Research has shown that ATG can lower the risk of organ rejection, with one study finding that ATG improved survival rates and reduced rejection episodes in liver transplant patients. TLI may help the body accept the new liver by calming the immune system, which otherwise might cause rejection. Experience with TLI in kidney transplants suggests it could benefit liver transplants as well. In this trial, participants will receive either synchronous or delayed tolerance regimens of ATG and TLI. These treatments aim to reduce the need for long-term use of immune-suppressing drugs, which often have many side effects.⁵⁶⁷⁸⁹