Defining Steroid-Refractory and Steroid-Dependent GVHD

Yi-Bin Chen, MD outlines the definition of steroid-refractory vs steroid-dependent graft-vs-host disease.


Yi-Bin Chen, MD: Steroid-refractory or steroid-dependent chronic graft vs host disease is common in the patients I see in my clinic [at Massachusetts General Hospital]. Part of the reason is likely because by the time we start treating chronic graft-vs-host disease, a good amount of end-organ damage has already set in. Patients and providers probably recognize it too late. There’s something to be said for early intervention, though it remains to be seen if we can find a system to do that accurately.

In patients who start systemic steroids for the initial therapy of chronic graft-vs-host disease, one-half to two-thirds of patients will require a second-line therapy. Some meet the definition of steroid refractory, which means that systemic steroids haven’t brought about a partial or less complete response. For any therapy that I start, I try to give it at least 3 months to see if it will work. Within those first few weeks, if the disease worsens, then they are steroid refractory once you start steroids. If you have an objective measure, like liver function tests, where there’s a number, then you can make this diagnosis rather accurately.

However, for much of chronic graft-vs-host disease, it’s more subjective assessments that are more difficult to figure out if something is bringing a better response. At the 3-month mark, if patients haven’t achieved a satisfactory response from a practical quality-of-life standpoint, we’ll move on to something else. By 1 month, if patients haven’t achieved the response at all, if there’s no change in their symptoms, or if they’re worsening, then that meets the definition of steroid refractory as well. There are shades of gray. Part of it is how serious the symptoms are and how much it affects the patient’s overall quality of life.

Steroid-dependent chronic graft-vs-host disease is a little different. That refers to a population that has achieved a response, and as we’re trying to lower the steroids, or taper them, we drop below a certain threshold that causes the symptoms of their chronic graft-vs-host disease to flare or worsen. If you increase the steroids to a certain dose, those symptoms will go away. In that patient, you’ve defined their dependence on a certain dose of steroids. Depending on what dose of steroids that is, that will drive your motivation to add a second-line therapy to ultimately be able to lower the steroids less than that threshold. If it’s at 5 mg a day, that’s a different story [compared with] 30 mg a day for 2 different patients.

Transcript edited for clarity.

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