Prophylactic Strategies in Graft vs Host Disease Management

EP: 1.An Overview of the Graft vs Host Disease Landscape

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EP: 2.Prophylactic Strategies in Graft vs Host Disease Management

EP: 3.An Overview of Treatment Options for Chronic GVHD

EP: 4.REACH-2 Trial of Ruxolitinib in Steroid-Refractory Acute GVHD

EP: 5.REACH-3 Trial of Ruxolitinib in Steroid-Refractory Chronic GVHD

EP: 6.The Evolving Treatment Landscape of Chronic GVHD

Transcript:

Corey Cutler, MD, MPH, FRCPC: GVHD [graft versus host disease] prophylaxis is universal. The only time that we don’t do prophylaxis is when you have a transplant from identical twins, or when you are using the patient as their own donor, or autologous transplantation. Aside from those 2 scenarios, GVHD prophylaxis is absolutely required. It comes in 2 forms, either pharmacologic or via graft manipulation. Pharmacologic GVHD prophylaxis is far and away more common in North America. The standard of care in matched related and matched unrelated donor transplantation is the combination of a calcineurin inhibitor, such as tacrolimus or less commonly cyclosporine, in combination with methotrexate. This is the tried, tested, and true standard in North America, but there are some alternatives that can be considered. The use of post-transplantation cyclophosphamide, which is used predominantly in haploidentical transplantation, has now been adapted to matched transplantation. Although it does not appear to offer much in terms of advantage based on recent studies such as the PROGRESS II trial from the Blood and Marrow Transplant Clinical Trials Network. Then other agents added to tacrolimus and methotrexate can be considered. At our center we use sirolimus, particularly in our reduced-intensity transplants. There are a lot of other experimental approaches to preventing acute graft versus host disease.

Then there is the entire strategy of graft manipulation. That can be done using drugs such as antithymocyte globulin, which is given to the patient to both deplete T cells in the donor and in the graft, or can actually be administered right into the bag in the case of agents such as Campath [alemtuzumab], the monoclonal anti-CD52 antibody, which can be administered both to the patient and within the bag, which is commonly done in the United Kingdom. Ex vivo T-cell depletion by either positive selection of CD34 cells or depletion of T cells is a strategy that has been employed and continues to be used at certain centers in this country but is largely falling out of favor to some degree because of the results of the recent PROGRESS II trial. Although that really examined one specific way of graft manipulation.

Despite prophylaxis, a significant portion of our patients, unfortunately, do end up having acute GVHD. In the matched related donor setting, the rates of acute GVHD are in the 25% to 35% range. In matched unrelated donor transplantation, those rates are a little bit higher, 30% to 40%, perhaps even up to 50%. In alternative donor scenarios, such as haploidentical transplant, rates have been reported between 30% and as high as 60% in some series for acute graft versus host disease. Cord blood transplant is associated with slightly lower rates of acute GVHD. What’s important to understand is that not all GVHD is severe. We do grade acute GVHD. The numbers I just quoted refer to all clinically significant GVHD, that is grades 2 to 4. The rates of severe or grade 3 to 4 GVHD are significantly lower and fall somewhere between 5% and 20%, depending on the scenario and the GVHD prevention regimen that one is using.

Transcript edited for clarity.