Inside the Clinic: Acute Graft-versus-Host Disease - Episode 16

Acute GVHD: An Evolving Treatment Paradigm


Corey S. Cutler, MD, MPH, FRCPC: There are a couple of other important considerations when we’re caring for patients with acute graft-vs-host disease [GVHD]. It turns out I’m attending on the ward right now, and we have a number of these patients. I think it’s important to not underestimate the other components of care that go into the patient with acute GVHD. We have to do meticulous wound care for skin disease. There’s the element of resting the intestinal tract and providing parenteral nutrition to feed the patients during their time course in the hospital with acute GVHD, and it’s really a multidisciplinary approach involving our dietitians, our physical therapists, our nurse colleagues, our research coordinators, and our research technicians and couching expectations with the patients. Understand that the patient is going to be in the hospital for several weeks should they be unfortunate to get acute acute graft-vs-host disease. Any comments on the supportive care of the acute GVHD patients you want to add?

Joseph Antin, MD: I just want to add to the multidisciplinary approach, that it’s critical to have our infectious disease colleagues involved. Because even in the absence of GVHD, patients in the early stages after transplant are quite immunocompromised and are subject to all sorts of bizarre and unexpected infections, in addition to the usual expected infections. In addition to that, many patients will get pneumonias and things of that nature. Our pulmonary colleagues were often quite helpful in that regard as well.

With respect to conventional supportive care, I think for skin involvement the dermatologists are often quite helpful in terms of not only coming up with topical regimens to ease the discomfort of the skin but also helping facilitate healing and reducing inflammatory manifestations of the skin. Of course, for somebody with very severe GVHD—what we would consider grade stage IV skin disease, blistering graft-vs-host disease—we sometimes have to have them in the burn unit because they can actually desquamate most of their body.

Stage IV skin GVHD is relatively uncommon, but severe intestinal graft versus host disease is quite common, and this is where we need to confirm these diagnoses by biopsy because there are a number of things that can simulate graft-vs-host disease. Adenovirus, cytomegaly virus, may not be apparent in the blood and may not seem like a conventional viral infection, but we can get intestinal involvement with these. Of course, if you’re treating an adenovirus infection with prednisone or CMV [cytomegalovirus] with prednisone without specifically targeting the virus, you may make things worse. These are extremely important corollaries, in addition to the conventional immunosuppression that we use, that we need to be aware of.

Corey S. Cutler, MD, MPH, FRCPC: I think you touched on a very important point about involving our colleagues from infectious disease. We certainly have made some strides in the management of acute GVHD, but over time probably the biggest contributor to our success in the last 10 to 20 years has really been the advent of broad-spectrum effective antifungal agents and the use of drugs that have CMV activity, both in the preventive and the therapeutic senses. We have, in fact, improved outcomes of graft-vs-host disease. There are analyses from the CIBMTR [Center for International Blood and Marrow Transplant Research], for example, that have documented that the outcomes of late-stage GVHD are improving. But I think we do have to ascribe some of our successes to our colleagues, particularly in infectious disease.

Joseph Antin, MD: Absolutely. As I think back over my career, in the early days it was amphotericin, which was a horror to administer. Twenty-five percent of our patients died of CMV. In our program we do about 275 allogeneic transplants a year, and maybe 1 or 2 die of CMV. Whereas in the previous era we would expect close to 75 to 100 of them to die of CMV. That’s how infection control, a critically important advent, has benefited our patients.

Corey S. Cutler, MD, MPH, FRCPC: What else? What are the next step in acute graft-vs-host disease? Where is our field moving, do you think, in the next few years?

Joseph Antin, MD: I think most of us would agree that prophylaxis is more important than therapy if we can maintain graft vs leukemia, if we can foster immunologic reconstitution and prevent graft-vs-host disease. This is the holy grail of transplantation: prevent GVHD, allow effective immune reconstitution, and provide an effective anticancer effect, then we win and our patients win. One of the newer regimens that is becoming increasingly popular is the use of post-transplantation cyclophosphamide. This is maybe 6 or 7 years old; it was a little counterintuitive.

It took a little while to catch on but actually has been very effective at controlling both acute and chronic graft-vs-host disease. We still don’t know to what extent the rest of the holy grail can be achieved; that is, these patients are extremely immunocompromised, and there may be some degree of loss of graft vs leukemia. What our group is focusing on are things like cancer vaccines. One of our colleagues, Vincent Ho, will generate a leukemia vaccine for the patient’s endogenous leukemia. We’re using that to foster the graft-vs-leukemia effect in the absence of acute graft-vs-host disease. We also have some cellular therapies; you might want to comment on natural killer cells, for instance.

Corey S. Cutler, MD, MPH, FRCPC: We’re working a great deal. Our colleague, Dr Rizwan Romee, is working and leading our efforts in providing cellular therapy against tumor relapse by generating interesting NK [natural killer]—derived cellular products. But I think what you’re trying to say is that simply solving acute graft -vs-host disease isn’t the big-picture answer. It’s taking care of the primary malignancy and putting GVHD in the place of preventing complications, preventing the disease from initial relapsing, and fostering long-term immunologic reconstitution and overall good health.

Joseph Antin, MD: I agree.

Corey S. Cutler, MD, MPH, FRCPC: Dr Antin, thanks very much for joining me here today at this OncLive Insights® session on acute GVHD. We went over some of our institutional practices. Notably, I learned most of these from you. But it’s been a pleasure talking to you today, and we hope all of you learned a little about this.

Transcript Edited for Clarity