Donor blood stem cells and T cells could help patients wean off immunosuppressive drugs after organ transplant

Dr. Samuel Strober is refining a process that eliminates the need for the many immunosuppresant drugs normally required after a transplant.
Image credit: Stanford Medicine News Center

In 2019, there were over 23,000 kidney transplants in the United States, according to figures from the United Network for Organ Sharing (UNOS). These transplants can be lifesaving, but the donated organ can be perceived as a foreign invader by the patient’s immune system and attacked. In order to protect the organ from attack, transplant recipients are required to take numerous drugs that suppress the immune system, which are referred to as immunosupressive (IS) drugs. Unfortunately, these drugs, while helping protect the organ, can also cause long term problems such as hypertension, diabetes, heart disease, infection, a high concentration of fats in the blood, and cancer.

To address this problem, Dr. Samuel Strober and his team at Stanford University are conducting a CIRM-funded clinical trial that gives patients getting a kidney transplant a mixture of their own blood cells and cells from the kidney donor, a process called mixed chimerism.

Pairing patients and donors for transplants is done via Human Leukocyte Antigen (HLA) matching. HLA are markers on most cells in your body and are used by your immune system to recognize which cells belong to the body. If you are fully HLA matched that means your cells and the donor cells are immunologically compatible, and so less likely to be rejected. If they are HLA haplotypes, it means they are close but not fully matched so rejection is more likely.

In the trial, fifty-one patients with end stage renal failure that had just received a kidney transplant were infused with blood stem cells (cells that can give rise to different kind of blood cells) and T cells (a cell that plays a role in the immune response) obtained from the donor to achieve a mixed chimerism. Of the 51 patients 29 were fully HLA matched, and 22 were HLA haplotype matched.

Standard IS drugs were administered to all the patients after transplantation and the patients were monitored from six to twelve months to ensure there was no organ rejection or graft vs host disease (GVHD), a condition where donated blood stem cells attack the body.

After this period, the patients were taken off the IS drugs and the results of this trial are very promising. Twenty-four of the fully HLA matched patients with a persistent mixed chimerism for at least six months were able to stop taking the IS drugs without evidence of rejection for at least two years. Ten HLA haplotype matched patients with a persistent mixed chimerism for at least twelve months were able to stop taking some of the IS drugs without rejection.

This is encouraging news for patients undergoing any kind of transplant, leading to hope that one day all patients might be able to get a life-saving organ without having to take the IS drugs forever.

The full results of this study were published in Science Translational Medicine.

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