A 53-Year-Old Man With Steroid-Refractory Acute Graft-Versus-Host Disease - Episode 4

Acute GVHD: Assessing Response to Steroid Therapy

Considerations for assessing response to steroid therapy as initial therapy for acute graft-versus-host disease and factors that impact next-line therapy, when necessary.

Michael Bishop, MD: In terms of considerations for treating the patient in our case presentation with steroids, I said he doesn’t have any other specific medical problems. The one thing I worry about is, what about that patient who has underlying diabetes mellitus, especially type 1 diabetes? While patients are on calcineurin inhibitors, we often uncover that they have underlying borderline type 2 diabetes. Calcineurin inhibitors inhibit insulin production and downregulate insulin receptors. Therefore, a lot of these patients have hyperglycemia.

So if you have a patient who’s already in that trouble and all of a sudden you add steroids, you know you’re in trouble. If the patient has bad hypertension, steroids will cause problems. Again, this patient had an ECOG 1 performance status, which would be a Karnofsky score of 70 to 80. The modified Glucksberg criteria are taking into consideration what the performance status is, although it has to be a pretty bad performance status to affect overall outcomes. But I’m worried about using steroids here, because it’s going to be debilitating to that individual.

And then finally and probably most importantly, does the patient have any active infections? When you start using big time steroids, you’re at increased risk for fungal infections and you’re going to suppress the patient. They’re going to be at increased risk for viral infections. All of those things play an important role when determining how much therapy and for how long, and whether I’m going to think about using alternative therapies. But my goal in almost every single patient is to get them off steroids as soon as possible.

In regard to determination of clinical response—there’s been a ton of research done on this—you want to see complete resolution in all organ involvement as an overall goal. We use the same staging system that we do for organs. Every time I see a patient in clinic who has graft-versus-host disease, we mark out what their maximum stage for each organ is and each grade. Every time we see them, we also look at what is happening with each of those organs. For example, if the patient’s BSA [body surface area] involvement was about 45%, and when I saw him it was down to 30%, that 30% still puts his condition at stage 2 disease.

I’m going to look at what their stool volume is. When the guy says, “I can’t count the number of times,” I make him maintain a strong diary. Then I know he was having stool volumes 8 to 9 times a day, and now that’s down to 5 to 6 times per day, and he is starting to get his appetite back. So for a clinical response, we want to see a downgrading in the organ system. But the other thing is we just want to see our patients doing better. If they’re able to function despite having active graft-versus-host disease, that’s an improvement, overall. However, I realize that likely can’t be sustainable for a long time.

Transcript edited for clarity.


Case: A 53-Year-Old Man With Steroid-Refractory Acute Graft-Versus-Host Disease

Initial presentation

  • A 53-year-old man presents on day +40 for a routine follow-up visit after matched donor peripheral blood stem cell transplant. He complains of a new rash, abdominal pain and ‘countless’ loose stools every day for the last 4 days
  • PMH: unremarkable
  • PE: Rash noted on arms and upper trunk (~45% BSA); diarrhea was quantified to about 1100 cc/day

Clinical workup

  • Labs: total bilirubin 2.6 mg/dl, AST 60 U/L, ALT 75 U/L, Hb 9.8 g/dl
  • Negative for HBV, HBV, CMV, EBV, HHV-6
  • Stool testing negative for bacterial/viral infection
  • Skin biopsy of the rash showed exocytosed lymphocytes, and dyskeratotic epidermal keratinocytes with follicular involvement
  • Colonoscopy with biopsy showed numerous apoptotic bodies in the crypt epithelium
  • He was diagnosed with acute GVHD:
    • Skin stage 2
    • GI stage 2
    • Liver stage 1
    • Modified Glucksberg Criteria: grade II; MAGIC Criteria: grade II
  • ECOG 1

Treatment

  • Initiated methylprednisolone 1.0 mg/kg and topical steroids
  • There was minimal response to treatment after 2 days, dose was increased to 2.0 mg/kg/day
  • Continued on systemic steroids for 5 more days; rash subsided minimally
  • He was started on ruxolitinib 5 mg PO BID, tolerated well; increased to 10 mg PO BID at day 3