Overview of Symptoms, Diagnosis, and Tools for Assessing the Severity of GVHDc

Case: A 58-year-old man with mild, steroid-refractory chronic graft-versus-host disease

Initial presentation

  • A 58-year-old man previously underwent myeloablative conditioning and PBSC allograft for acute lymphocytic leukemia
  • Received tacrolimus and methotrexate for GVHD prophylaxis
  • 10 months post-transplant patient developed moderate muscle and joint pain with decreased range of motion, mild erythematous rash on cheeks

First-line treatment

  • Patient received topical steroid cream for rash and started oral prednisone 1 mg/kg/day
  • After 4 weeks of treatment, the patient’s rash disappeared but muscle/joint pain persisted

Second line treatment

  • Patient is now receiving ruxolitinib 10 mg orally twice daily, plus steroids 1 mg/kg/day

Pashna Munshi, MD: At first, most patients present with inflammatory skin changes. They may have tenderness or dry mouth; they may have dry, irritated eyes; they may have liver dysfunction or transaminitis with eosinophilia. And these are usually easily controlled with initial steroids, but often when we try to taper the steroids the symptoms can return. Other manifestations may be less frequent, and they are slightly more difficult and difficult to control overall. These can be skin sclerosis or joint tightening, immobility, fasciitis, bronchiolitis syndrome, which occurs in the lungs. They may have painful mouth ulcers that are unresponsive to local treatments, severe dry eyes, gastrointestinal involvement, etc.

Acute GVHD [graft-vs-host disease] has fairly rapid costs, with acute symptoms, namely diarrhea, or this very intense rash that people develop, or liver abnormalities. It’s right there in your face, kind of a symptom, and easy to notice, and therefore easy to start actionable things like treatment. But when it comes to chronic GVHD, sometimes it can be more subtle, especially with changes in the skin, with tightening and sclerosis that can manifest in the patient. And before they know it, they may have trouble raising their arm, extending their arm fully overhead, or bending down, for example, if they develop multiple sclerosis. of their abdominal wall. Therefore, I find that in situations where it is a more protracted case, early identification of chronic GVHD becomes a challenge. In addition, many of these patients far from their transplant may not be followed systematically and they often have an appointment a month apart. Perhaps they are seen in a community setting rather than a transplant program, and sometimes these subtle changes can be missed, and there are nuances in identifying these symptoms and signs.

The NIH [National Institutes of Health] Consensus conferences were developed in 2005 and 2014, and most recently in 2020, with the aim of standardizing the reporting of response assessments, as well as severity scores for clinical trials. And then they made recommendations, which are now widely adopted in clinical practice. And we use these clinical criteria to classify and stage chronic GVHD. Most often, the organs are rated on a scale of 0 to 3, where 0 corresponds to the absence of damage and 3 to the severity of the damage. The final score is then based on the degree of damage to individual organs, resulting in an overall severity score. And based on that, you can either have a mild, moderate to severe score, and studies have shown that people with mild GVHD, a mild overall score, have a good overall prognosis, while those with severe disease [are] associated with higher treatment-related mortality and lower survival.

Transcript edited for clarity.

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