Overview of Acute and Chronic GVHD


Nelson J. Chao, MD, gives an overview of acute and chronic GVHD, and details the classical presentation and staging process.

Case: A 35-Year-Old Woman with Chronic GVHD

  • A 35-year-old woman received busulfan and cyclophosphamide conditioning prior to a matched unrelated donor peripheral blood stem cell transplant for acute myeloid leukemia; tacrolimus and methotrexate were administered as graft-vs-host disease prophylaxis.
  • PMH of type 2 diabetes.
  • Post-transplant, experienced the following:
    • +1 month post-transplant, grade II acute skin GVHD, resolved with glucocorticoids
    • +6 months post-transplant, grade I vaginal dryness, treated with topical estrogen
    • +11 months post-transplant, grade I dry eyes/foreign body sensation, treated with lubricating eye drops
  • Now, + 12 months post-transplant, grade 2 muscle and joint paint that limits daily exercise routine, treated with prednisone
  • Supportive care and counseling provided
  • 1 mg/kg/day prednisone tapered to 0.25 mg/kg/day
  • During steroid taper, patient developed grade 2 mouth symptoms with ulceration and lichenoid features as well as maculopapular rash/erythema on lower torso (BSA 10%)


Nelson J. Chao, MD: The difference between acute and chronic was originally historic: acute was always thought to be within the first 100 days, and chronic was what happened after the first 100 days. It’s clear biologically that that’s not true. There are patients who developed chronic GVHD [graft-vs-host disease] before day 100, and patients who develop acute GVHD after day 100. The clinical manifestations of acute and chronic [GVHD] are different. Acute [GVHD] tends to be much more of a cytokine-driven response, whereas chronic GVHD is more autoimmune-type, fibrotic-type changes.

The incidence of acute [GVHD] in the calcineurin inhibitor methotrexate area is 50% to 60% of grade 2 or greater, and the incidence of chronic [GVHD] is 50% to 60%. The risk factors that increase the potential of developing graft-vs-host disease are an HLA mismatch, older age, a multiparous female donor into a male recipient using peripheral blood rather than bone marrow, and not using an adequate GVHD prophylaxis. And the more intensive the conditioning, the higher the risk of GVHD.

We do use prophylaxis for acute [GVHD], and successful prophylaxis for acute [GVHD] is probably the best prophylaxis for chronic [GVHD] because they tend to go hand in hand. The highest risk for developing chronic GVHD is having had acute GVHD. Prophylaxis for acute GVHD prevention is on the order of about 40% to 50%.

The classic symptoms, according to the NIH [National Institutes of Health] consensus criteria, are the involvement of those 9 organ sites. Those are the skin, mouth, GI [gastrointestinal] tract, liver, lungs, joints, fascia, and female genitalia. Remember, the score is 0 to 3: 0 is no involvement. For the mouth, a score of 1 would be mild symptoms without any significant limitation of oral intake. A score of 2 would be moderate symptoms with partial limitation of oral intake, and a score of 3 would be severe symptoms with the major limitation of oral intake. You can see that each of these organs would have a moderate amount to a severe amount and that’s how we would add up the extent of chronic GVHD.

The challenge of this system is that it takes time, but it allows you to use this over and over to get a better sense of what’s happening for the patient. It’s not very granular, as you can see. A score of 1 is a little bit, a score of 2 is a little more, and a score of 3 is a lot. But if you add together all the organs involved, you get a reasonable sense of how advanced or severe that patient is with chronic GVHD. What’s missing is a better overall global assessment. It’s missing a performance status that would be helpful to add to this staging system. Given that this patient has a score of 2 in the fascia, that would be felt to be moderate chronic GVHD.

Transcript edited for clarity.

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