Role of GVHD Prophylaxis

EP: 1.Overview of Graft-Versus-Host Disease

EP: 2.Diagnosis of Acute and Chronic GVHD

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EP: 3.Role of GVHD Prophylaxis

EP: 4.Initial Therapy in GVHD

EP: 5.Treatment for Steroid-Refractory Acute GVHD

EP: 6.Treatment for Steroid-Refractory Chronic GVHD

EP: 7.Emerging Therapies for Acute and Chronic GVHD

EP: 8.Unmet Needs in GVHD

Corey S. Cutler, MD, MPH, FRCPC: All patients undergoing transplantation require and receive some form of GVHD [graft-vs-host disease] prophylaxis. The GVHD prophylaxis in North America is for the most part pharmacologic. It’s generally based on a calcineurin inhibitor drug regimen, either tacrolimus or cyclosporine, but more commonly tacrolimus in North America. Tacrolimus is most commonly given with methotrexate or other agents, such as mycophenolate or sirolimus. There are other ways of preventing GVHD with pharmacologic prophylaxis as well. The most recently used regimen is the post-transplantation cyclophosphamide regimen, where the chemotherapeutic agent cyclophosphamide is given on the third and fourth days following transplantation, and then additional agents, such as tacrolimus, sirolimus, or mycophenolate, are administered for the next few weeks or months.

There are also nonpharmacologic ways of preventing acute graft-vs-host disease. Those involve manipulation of the graft, either with in vivo or ex vivo T-cell depletion. One can take the T cells out of the graft using bead columns to either positively select the stem cells or negatively select the T cells. You can also use drugs like ATG [antithymocyte globulin] or Campath [alemtuzumab], which are given to the recipient. Those drugs function to deplete T cells from both the host as well as the graft. Those are the ways we can prevent graft-vs-host disease. There are a number of new ways we are looking to prevent GVHD with novel pharmacologic agents and even newer graft manipulation strategies. What’s very encouraging is that these are now being tested in randomized phase 3 trials. While none are currently the standard of care, it’s hoped that in the next couple of years as we get the results of these phase 3 studies, the standard will evolve in graft-vs-host disease.

Haris Ali, MD: GVHD prophylaxis is prescribed to all of the patients. However, the intensity can differ. There are different types of GVHD prophylaxis. Usually they have a backbone of one of the calcineurin inhibitors, which could be tacrolimus or cyclosporine, and it is combined with any of the other agents: either sirolimus, methotrexate, CellCept [mycophenolic acid], or post-transplant Cytoxan [cyclophosphamide]. They are decided based on the institutional preference and expertise, but there are also situations where one might be used over the other. For example, we mostly use post-transplant Cytoxan in the haploidentical donor; that’s how these studies were done, using high doses of post-transplant Cytoxan. Generally speaking, the most common ones used are tacrolimus and methotrexate, tacrolimus and sirolimus, and post-transplant Cytoxan along with a combination of cyclosporine with CellCept. They can be used interchangeably for most patients.

Transcript Edited for Clarity