When the Treatment Fights Back

June 29, 2012 | Melissa Marino

Graft-versus-host disease (GVHD) – the main complication of allogeneic stem cell transplants – is the exact opposite of solid organ rejection: instead of your body rejecting the new organ, the new organ (the donor immune system) rejects you.

In the acute post-transplant period, GVHD typically manifests as an itchy skin rash, gastrointestinal symptoms like nausea, vomiting and diarrhea, or liver dysfunction with jaundice – but if the condition becomes chronic, it can wreak havoc on any organ system.

Vanderbilt-Ingram researchers are investigating how GVHD develops and looking for ways to predict who will be affected by GVHD as well as how to potentially prevent or treat the condition.

Brian Engelhardt, M.D., MSCI, studies the role of immune cells in GVHD.

In a stem cell transplant, mature donor immune cells (primarily T cells) come along as “passengers” with the donor stem cells (graft). These mature cells serve important functions, like helping the stem cells take up home as their new host’s bone marrow and serving as the patient’s initial immune system after the transplant. But one subtype of T cell, Th1 cells (“inflammatory T cells”), are the main instigators of early GVHD, Engelhardt says.

He and his colleagues are studying the role of inflammatory T cells and the “good guy” T cells known as regulatory T cells (Tregs) in the course of GVHD.

“The goal is to predict who is going to get GVHD prior to the clinical development of disease,” says Engelhardt, an assistant professor of Medicine. “If we have this biomarker, we can begin treatment early to prevent GVHD from developing – or try to increase the number of functional Tregs to regulate the immune system.”

One promising therapy, called photopheresis, involves collecting the patient’s white blood cells (which, post-transplant, come from the donor), exposing them to UV light, and infusing them back into the patient.

The UV light appears to kill off the inflammatory T cells but has recently been shown to also increase Tregs, Engelhardt notes.

“We’ve actually shown some pretty encouraging results (with photopheresis),” says Madan Jagasia, M.D., director of the Outpatient Transplant Program and section chief for Hematology and Stem Cell Transplant at Vanderbilt-Ingram. “It’s a neat thing because you’re not penalizing the patient with any additional chemotherapy or steroids.”

Diabetes is another post-transplant complication that appears intricately linked to immune function. It develops in 30 percent to 60 percent of patients. Sometimes it resolves on its own, but about 10 percent to 30 percent of patients will have diabetes long-term.

Engelhardt and colleagues are also trying to identify predictors of post-transplant diabetes and therapies to prevent the condition and/or reestablish normal immune function.

“The better your immune system functions after transplant, the more likely you’re going to have a positive outcome after transplant,” says Engelhardt. “That means less GVHD, less infectious complications, less metabolic disturbances, and therefore likely improved transplant outcomes, which means improved survival and improved quality of life, which is important for our patients.”

 

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