Graft Versus Host Disease Treatment Advances - Episode 4
Centering discussion on a scenario of acute graft vs host disease, expert panelists consider optimal workup of a patient showing signs of GVHD.
Yi-Bin Chen, MD: Let’s shift to a couple of the cases that we have. We’re going to go with case No. 1. This is a hypothetical 44-year-old man. He underwent a myeloablative conditioning, matched unrelated donor, peripheral blood stem cell transplant for an underlying diagnosis of acute myeloid leukemia. He received standard tacrolimus [Prograf] and methotrexate [Rheumatrex] as graft versus host disease [GVHD] prophylaxis. The donor was a CMV [cytomegalovirus] SEER-positive 48-year-old woman with 2 children. On day 26 after the transplant, the patient presented with a macular papular rash on his face, chest, forearm, shoulders, and back. It was estimated to involve approximately 60% of his body surface area. He also was experiencing, upon further questioning, 3 to 4 episodes a day of watery diarrhea, which is a little bit looser than what he was having in the past week. These GI [gastrointestinal] symptoms have been going on for 2 days. Do you think this is a typical presentation of acute GVHD? What would you do for evaluation and work-up for this patient?
Amin M. Alousi, MD: I’m still a firm believer that any patient early post transplant presenting with diarrhea has GVHD until proven otherwise. I believe this needs prompt—emphasis on prompt—evaluation and work-up. Generally that would include admission to the hospital and expedited endoscopies done with biopsies. Obtaining stool to rule out infectious ideologies or other medications…is part of that evaluation, but more times than not, this is going to turn out to be GVHD-related and getting prompt evaluation for it is important. I believe diarrhea is a high-risk manifestation of GVHD because we know that there’s a preponderance of lower GI GVHD in the steroid refractory setting, and we believe treating these patients early is important.
Yi-Bin Chen, MD: Let’s say you admit this patient to your hospital and the symptoms involved are rash and GI symptoms. You reach an impression that this does represent acute GVHD. Can you describe how we classify, or stage, or grade GVHD?
Amin M. Alousi, MD: Sure. If I understood the case correctly, the patient had 2 episodes per day of diarrhea.
Yi-Bin Chen, MD: It was 3 to 4 episodes per day, but feel free to assign a volume as well if he’s in the hospital.
Amin M. Alousi, MD: The fact that there’s a skin rash as well as diarrhea increases the likelihood that this is going to be GVHD related. Importantly, the Harris criteria that came out of the MAGIC consortium allow us…to apply staging. Provided that each of those 3 to 4 episodes was liquid stool, and that the definition of diarrhea is stool that could be poured, we could estimate this patient to have a stage I lower GI involvement. In terms of skin rash, we’re going to assess the body surface area, and if it’s less than 25%, then it’s stage I; 25 to 50%, stage II; but more than 50%, stage III. If there’s any evidence of separation of the dermis from the epidermis, or a bullous lesion, this would be stage IV. This patient’s looking at a minimum of having stage I lower GI GVHD. Did you give me a body surface area for the rash?
Yi-Bin Chen, MD: 60%.
Amin M. Alousi, MD: He is going to have stage III skin involvement of his GVHD. In terms of further assessments of the stage, we could then apply the Modified Minnesota Grading Scheme to this and determine if this is so-called “standard risk versus high risk.” By Minnesota criteria, this patient would qualify as standard risk. I would add a caveat that an analysis that we did at The University of Texas MD Anderson Cancer Center looked at patients who presented with stage I lower with concurrent skin rash and found that indeed these patients have a more high-risk phenotype. In fact, this patient would qualify for the multicenter CTN trial for high-risk acute GVHD based on that data. Although the volume of stool is only stage I, the combination of stage I lower with concurrent skin rash may suggest this patient is slightly more high risk than what would be traditionally assigned based on the Modified Minnesota Grading Scheme.
Yi-Bin Chen, MD: I agree with you. Part of the problem for this patient is when we treat him. We’re just seeing him at presentation. Most analyses, including the big analyses that define the Minnesota criteria, classify patients based on their maximal stage of GVHD, which you obviously don’t know when the patient presents. This patient could be going on 4 days or later and having 2 liters of diarrhea, and that’s a completely different story than how he’s presenting right now. It’s a huge problem in GVHD to prognosticate these patients because we’re trying to do studies that classify patients based on biological risk.
Transcript edited for clarity.