Monday, October 10, 2011

Enter the Chimera

I've had the privilege of being a part of the care team for several patients who have participated in Stanford's Immune Tolerance program here in Palo Alto. The idea behind the program is pretty cool: create chimerism (the immune state, not the mythical beast) in the kidney transplant recipient in order to facilitate long term immune tolerance allowing the discontinuation of immunosuppressant medications.

Nate posted on the Mass General program for combined kidney and bone marrow transplants back in 2009 with reference to the original NEJM report from 2008. This past week in NEJM our fellowship director, John Scandling along with the transplant and basic science groups, reported on the followup of the initial 12 patients to undergo the protocol here at Stanford.

The protocol is incredible. Patients receive 10 doses of total lymphoid irradiation targeted to the lymph nodes, spleen, and thymus, and five doses of rabbit antithymocyte globulin during the first 10 days after kidney transplantation readying the recipient immune system for donor immune cell engraftment. Donor CD34+ cells and a defined dose of T cells are then given to the kidney recipient on day 11 in order to create the new "chimeric" bone marrow.

All patients get MMF for 1 month and cyclosporine for at least 6 months. Cyclosporine is discontinued as long as persistent chimerism can be demonstrated and there is no clinical or biopsy evidence of kidney rejection or graft-versus-host disease.

Seven of the initial 12 patients are now completely off immunosuppressant drugs without clinical or biopsy evidence of kidney rejection. One patient, who was off immunossupresant drugs for three years died suddenly while exercising four months after a myocardial infarction. Four patients continue to receive immunossupresant drugs because of recurrence of FSGS in one and episodes of rejection during the tapering of cyclosporine in the others.

The original protocol was applied to folks with perfectly HLA matched donors. These patients likely would have had excellent outcomes and allograft survival independent of chimerism but the protocol allows them to avoid the risks, side effects, expense and adherence issues that come with long term oral immunosupression. Patients with one mismatched HLA haplotype living donors have now entered the program and hopefully will be able to experience similar benefits.


Anonymous said...

This is the future, but the Mass. protocol (previously posted) has perhaps greater potential to overcome mismatched organs and thereby expand the inadequate supply.

Chimerism (perhaps via porcine thymus transplant) may also be an essential link in making xenotransplantation feasible.

Anonymous said...

This is a very upfront heavy protocol in terms of radiation and immunosuppression in a haploidentical population that currently experiences excellent survival on minimum immunosuppression.