Donor Chimerism and Graft Survival Following Combined HLA-Identical Sibling Living Donor Kidney and Hematopoietic Stem Cell Transplantation Utilizing a Conditioning Regimen of Total Lymphoid Irradiation and Rabbit Anti-Thymocyte Globulin
Jeffrey Veale, MD
Summary
The purpose of this study is to find out if an investigational treatment will allow kidney transplant recipients to better accept their new kidney and stop immunosuppressive medicines. This study is for kidney transplant recipients who receive a kidney from a sibling donor. The investigational treatment is started after kidney transplant. It begins with a regimen of a drug called rabbit anti-thymocyte globulin (rATG) combined with radiation therapy (known as total lymphoid irradiation, or TLI) to the lymph nodes and spleen. This is followed by an infusion of blood stem cells, which will be donated by the same sibling who donated their kidney. Researchers think that this treatment allows immune cells from the donor and recipient to live side by side, a condition referred to as "mixed chimerism." Mixed chimerism may help create a state of "tolerance" in kidney transplant recipients in which all immunosuppressive medications can be stopped without rejection of the transplanted kidney. This study will test whether (1) the investigational treatment will allow patients to stop immunosuppressive medications after their kidney transplant and (2) if the treatment impacts the rate of kidney rejection and the side effects of immunosuppressive medications.
Description
In spite of the pronounced benefit of kidney transplantation in prolonging survival and improving the quality of life of patients with end stage renal disease, it is still hampered by the risk of graft rejection and the need for lifelong immunosuppression. Researchers have sought to circumvent these challenges through the use of combined kidney and hematopoietic stem cell transplantation to induce immune tolerance. This study will build upon published reports showing favorable results for the TLI/rATG regimen in HLA-matched living donor transplant recipients. The investigators seek to confirm…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Recipient Inclusion Criteria: 1. Males and females ages 18 years and older receiving living donor kidney transplant from an HLA-identical sibling at UCLA Medical Center. 2. Agrees to participate in the study and is able to give informed consent. 3. Resides or is willing to stay within 3 hours distance from UCLA Medical Center by ground transportation for the first three to six months of the trial at the physician's discretion. 4. Meets institutional criteria for kidney and HSPC transplant. 5. No known contraindication to administration of rATG or radiation. 6. If patient is a female of reprod…
Interventions
- BiologicalDonor CD34+ and CD3+ cells
Infusion of GCSF-mobilized, Miltenyi-enriched CD34+ hematopoietic stem/progenitor cells (HSPCs) (≥ 5 million cells/kg) and CD3+ cells (5 million cells/kg) from an HLA-identical sibling living donor, following pre-conditioning regimen of rATG and TLI.
Location
- University of California, Los AngelesLos Angeles, California