Clinical Burden of Chronic GVHD
Risk factors associated with chronic graft-vs-host disease, and insight regarding how the condition commonly presents in patients.
Parameswaran Hari, MD, MRCP: Now we’ll be moving to the third segment, our main segment, on chronic graft-vs-host disease [GVHD]. Let me go back to Yi-Bin. In my experience, in actual practice, the single biggest predictor of chronic GVHD is whether a patient had acute GVHD. If you think of the patients getting chronic GVHD, there are people who never got acute GVHD and then they’re off of immune suppression and start developing chronic GVHD. Then there are people who merge from an acute GVHD that’s either inadequately controlled or merging overlapping into a chronic GVHD. Could you talk a little about the risk factors of chronic GVHD, going from graft source to everything else? What’s the clinical presentation of chronic GVHD?
Yi-Bin Chen, MD: A lot of the clinical risk factors for chronic GVHD mirror the clinical risk factors for acute GVHD, which is probably why it translates that those who had acute will get chronic. From the outset, all other things being equal, HLA [human leukocyte antigens] matching is traditionally the most important factor between donor and recipient. Conditioning regimen intensity is another factor. Myeloablative regimen yielded more acute and chronic graft-vs-host disease than reduced intensity, though that’s much more in the acute than the chronic sense.
The specific clinical risk factors for chronic GVHD have been proven in a randomized trial, BMT CTN 0201. This had myeloablative unrelated donor transplants randomized between peripheral blood stem cells and bone marrow as the graft source. Patients who received a peripheral blood stem cell source had a significantly higher rate of chronic graft-vs-host disease as well as increased severity. This later translated in long-term follow-up to patients who had received bone marrow being more productive and back to work, likely mediated by chronic graft-vs-host disease.
Graft sources have certainly played a role as well. We’ve seen analyses showing that umbilical cord blood, which is a naturally T-cell depleted product, also has less of an incidence of chronic graft-vs-host disease out back compared with the conventional regimens. Acute graft-vs-host disease certainly plays a big role. It sets the table for alloreactivity, and thus gets translated later.
There’s been a lot of work done that has yielded the whole B cell arm of chronic graft-vs-host disease. We tend to think of acute as a T-cell immune system pathway. Chronic is far more complicated, but recent work has illustrated this whole B-cell pathway for some patients, and that led to the basis behind why gender possibly matters when you think about chronic graft-vs-host disease. If you’re a male recipient and receive a graft from a female donor, there’s good research showing the existence of anti-Y-chromosome antibodies that serve as a marker for developing chronic graft-vs-host disease.
Those are the general clinical risk factors that we think about and have also yielded a bit of insight into developing treatments. But it’s important to realize that the genesis of chronic GVHD is at the time of transplant. That’s when the alloreactivity happens and sets the stage for what happens. We know this because if we deplete T cells at the beginning, we don’t see chronic out back a year later. It’s a really interesting phenomenon to think about.
Parameswaran Hari, MD, MRCP: Those are crucial points to make. And that explains why we have less chronic GVHD in the post-transplant cyclophosphamide setting, too.
Transcript edited for clarity.
