Experts on graft-vs-host disease review GVHD and methods of prophylaxis preceding transplant.
Preet M. Chaudhary, MD, PhD: Dr Tam, tell us a little bit about graft-vs-host disease [GVHD].
Eric Leon Tam, MD: In an allogeneic stem cell transplant, we’re using a donor and trying to replace the blood and the bone marrow in the recipient. A lot of complications can happen, but when we move the blood over we’re also moving over the entire immune system. Obviously, the immune system has to adjust and adapt to the new body. If the new system doesn’t fully adjust or adapt, and it starts to attack tissues in the body, such as the skin, the liver, or any other organ tissue, that’s considered graft-vs-host disease. We have to be very careful not to activate the immune system and to do our best to suppress it at least until the immune system can accommodate and adapt to the new host.
Preet M. Chaudhary, MD, PhD: How is it related to graft-vs-leukemia [GVL]?
Eric Leon Tam, MD: That’s a good question. Graft-vs-host disease and graft-vs-leukemia are always going to be interlinked. That’s because the overall effect that we want from the transplant is to have the immune system from the donor attack and keep the leukemia away by recognizing it as foreign and different. At the same time, we don’t want it to react to normal tissue. Graft-vs-leukemia is a favorable effect. That’s what we’re counting on to help keep the patient in remission. Graft-vs-host disease, however, can flare up. The more graft-vs-leukemia effect you push for, the higher the risk for graft-vs-host disease and vice versa. If you try to minimize graft-vs-host disease too much, you might sacrifice too much of the graft-vs-leukemia effect.
Preet M. Chaudhary, MD, PhD: A little graft-vs-host disease is good, but it could be too much if it gets out of control.
Eric Leon Tam, MD: Anecdotally, we feel that way. That at least tells us that the donor immune system is active. It may not be attacking the right thing, and it doesn’t guarantee that it’s attacking the leukemia, but at least we know the immune system is responsive and active.
Preet M. Chaudhary, MD, PhD: Dr Tam, tell us a little about the different transplant preparation regimens and GVHD prophylaxis regimens that you use in your practice.
Eric Leon Tam, MD: When we talk about allogeneic stem cell transplant conditioning, there are typically 3 categories. Nonmyeloablative is the lightest, and then we have reduced intensity and myeloablative conditioning. These are usually combinations of chemotherapy with radiation, sometimes with immunotherapy. How we decide which we regimen pick depends on the patient—their status, their age, their comorbidities, the disease status, whether they’re in remission or not, their risk for GVHD, the types of donors they’re using. All that comes into play. At our center, we have a very involved discussion about each patient to decide the best conditioning. Typically, we use radiation, chemotherapy, and immunotherapy.
Preet M. Chaudhary, MD, PhD: What are the general approaches with GVHD prophylaxis?
Eric Leon Tam, MD: The backbone of GVHD prophylaxis typically includes a class of medications called calcineurin inhibitors. This includes tacrolimus, cyclosporin, and sometimes mTOR inhibitors with sirolimus. The principle is to inhibit the immune system enough so that as the new donor cells graft and grow, we release them slowly over time so you don’t get a burst of immune system response recognizing the new host tissue, causing GVHD. The regimens for this start at the point of infusion of the new cells. We carry that on for 3 or 6 months at a minimum.
The beauty of allogeneic stem cell transplants compared with solid organ transplants is that immunosuppression isn’t expected to be lifelong. The immune system is adaptive and can learn to adapt to the host. Over 6 months, we’ll test and see. If the patient is doing well, we’ll try to reduce and eventually taper off and discontinue all medications. We don’t have to commit a patient to lifelong immunosuppression.
Preet M. Chaudhary, MD, PhD: Are there any new emerging treatments or strategies for GVHD prophylaxis?
Eric Leon Tam, MD: Definitely. New drugs are being approved by the FDA all the time, including 1 less than 6 months ago. Clinical trials continue to evolve around how to reduce the risk of GVHD. They’re looking at different things, including immunosuppressive medications but also medications that decrease scarring for chronic GVHD prophylaxis. Decreasing the level of immune system T cells sometimes helps decrease the risk of GVHD as well.
Transcript edited for clarity.