Overview of cGVHD Symptoms, Diagnosis, and Tools for Severity Assessment

Video

An overview of common symptoms, diagnostic challenges, and tools for severity assessment of chronic graft-versus-host disease.

Case: A 58-Year-Old Man With Moderate Steroid-Refractory Chronic Graft-Versus-Host Disease

Initial Presentation

  • A 58-year-old man previously underwent myeloablative conditioning and an allogeneic PBSC transplant for acute lymphocytic leukemia
  • Received tacrolimus and methotrexate for GVHD prophylaxis
  • At 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 was started on oral prednisone at 1 mg/kg/day
  • After 4 weeks of treatment, the patient’s rash resolved but muscle/joint pain continued

Second-line Treatment

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

Pashna Munshi, MD: At onset, most of the patients present with some inflammatory skin changes. They can have oral sensitivities or dryness; they can have dry, irritated eyes; they can have liver dysfunction or transaminitis with eosinophilia. And these are typically easily controlled with upfront steroids, but oftentimes when we try to taper steroids, the symptoms can recur. Other manifestations can be less common, and they are slightly more difficult and challenging to control overall. These could be skin sclerosis, or tightening at the joints, immobility, fasciitis, bronchiolitis syndrome, which happens in the lungs. They can have oral ulcers that are painful and unresponsive to local therapies, severe dry eyes, gastrointestinal involvement, and so forth.

Acute GVHD [graft-vs-host disease] presents with rather 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, sort of a symptom, and easy to notice, and easy to, therefore, start actionable items like treating. But when it’s chronic GVHD, sometimes it can be more subtle, especially with changes to skin, with tightening and sclerosis that can creep up on the patient. And before they know it, they may find it difficult to raise their arm, extend their arm entirely over their head, or bend downwards, for example, if they’re developing sclerosis of their abdominal wall. Therefore, I find that in those situations where it’s a more protracted case, early identification of chronic GVHD becomes a challenge. Additionally, a lot of these patients far out from their transplant may not be followed routinely, and they often have an appointment a month apart. Maybe they’re seen in a community setting rather than a transplant program, and sometimes these subtle changes can be missed, and there are nuances to the identification of these symptoms and signs.

The NIH [National Institutes of Health] consensus conferences were developed in 2005 and 2014, and most recently in 2020, in an effort to standardize the reporting of response assessments, as well as severity scores for clinical trials. And then they made recommendations, which are now largely adopted into clinical practice. And we use these clinical criteria for grading and staging of chronic GVHD. Most frequently, the organs are scored on a 0 to 3 scale, where 0 is no involvement, and 3 is the severity of involvement. The final score is then based on the degree of individual organ involvement, and this yields a global severity score. And based on that, you can either have a score of mild, moderate to severe, and studies have shown that people with mild GVHD, a global score that’s mild, have overall good prognosis, whereas those with severe diseases [are] associated with higher treatment-related mortality and lower survival.

Transcript edited for clarity.

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