Combined Kidney/Bone Marrow Transplants

One of the interesting ongoing protocols at the Massachusetts General Hospital Kidney Transplant Program is the combined kidney/bone marrow transplant protocol. The idea here is to transplant both kidney & hematopoeitic stem cells from the same donor, which will hopefully induce a state of immune tolerance that allows a sparing (and ideally a complete cessation) of immunosuppressive drugs without inducing rejection. The protocol would be most useful in younger patients who want their kidney transplants to last for as long as possible–with a goal of minimizing the use of calcineurin inhibitor therapy, which we know can lead to progressive allograft toxicity over the long-term.

As described in this recent review by Megan Sykes, nonmyeloablative regimens are given–with the goal of not being so toxic as to result in marrow failure but sufficiently strong enough to overcome the potential reactivity of T-cells reactive to the HLA-mismatched donor stem cells. Apparently the key is to generate a state of mixed chimerism (some bone marrow cells from the recipient, some from the donor) to prevent rejection and avoid complications such as graft-versus-host disease.

In the following 2008 NEJM article, five patients with ESRD underwent a combined kidney/bone marrow transplant. This pilot study has been declared a relative success given that four of the five patients have successfully been weaned off of immunosuppression, without rejection, over a follow-up period of between 3-6 years.

Interestingly, some of the patients enrolled in this protocol develop a delayed graft function, with biopsies that look like rejection. Shouldn’t these patients be LESS prone to rejection given that matched nature of the kidney & stem cells transplanted as well as the additional myeloablative therapy that is given beforehand? It turns out that the stem cell transplantation process is associated with a “cytokine storm”-type situation which may render the patient at high risk for allograft damage in the immediate post-setting. Fortunately, this appears to be a transient issue and most of the time the allograft function recovers nicely.