Case Overview: Steroid Refractory aGvHD


Yi-Bin Chen, MD, provides an overview of the case of a 50-year-old woman with steroid-refractory acute GvHD, including initial presentation, clinical work-up, and treatment.

Yi-Bin Chen, MD: Hello. I’d like to welcome everybody to our Targeted Oncology™ case discussion. We have a very interesting case illustrating current standards of treatment and evaluation for steroid-refractory acute graft-versus-host disease.

I’ll start with a case. This is somewhat based on a true story. This is a typical case that we see for those who take care of transplant patients. We have a 50-year-old woman who presents on day 32 for a routine follow-up visit after a myeloablative matched unrelated donor peripheral blood stem cell transplant for underlying diagnosis of acute myeloid leukemia in first remission.

When she comes into the office, she complains of a new, erythematous macular rash that had developed over the last 3 days and some mildly loose stools, which she estimates are approximately a little less than 0.5 L in the previous 24 hours, though obviously it’s a bit difficult to estimate that.

Her past medical history is not significant. She’s healthy otherwise and was a very active person before her diagnosis of leukemia. Her therapy for leukemia was rather uncomplicated until she proceeded to transplant.

On physical exam, I noted the aforementioned rash, which had a distribution on her neck, shoulders, and upper trunk. By estimation, it covered about 60% of her body surface area. Further clinical work-up that came back showed laboratory values significant for a total bilirubin of 2.7 mg/dL, with mildly elevated transaminases around twice the upper limit of normal.

Given this presentation, we admitted her to the hospital for inpatient expedited work-up with the suspicion that these findings could represent the initial onset of acute graft-versus-host disease. With our first battery of tests that we sent in the first 24 hours, we found that her stool testing was negative for any bacteria or viral infections, including C. diff [Clostridium difficile]. Blood tests were negative for any evidence of infection or reactivation of viruses, including hepatitis B and C, CMV [cytomegalovirus], EBV [Epstein-Barr virus], as well as HHV6 [human herpesvirus 6].

We did perform a biopsy of the affected area, and it came back showing sparse inflammation and abundant dyskeratotic keratinocytes. Given her diarrhea present in the hospital, which went along with her estimated volume of about 400 to 500 cc in 24 hours and was quite watery, we did ask our colleagues in GI [gastrointestinal] to perform a flexible sigmoidoscopy with random mucosal biopsies. Macroscopically, we did see some areas of patchy erosive ulceration in her sigmoid colon. The biopsy itself showed an inflammatory infiltrate with evidence of cryptitis and apoptosis.

Based on these findings, she was diagnosed with the initial onset of acute graft-versus-host disease. In terms of consensus staging criteria, given the body surface area of her skin, she will be a skin stage II. Given the volume of her diarrhea was less than 500 cc a day, she’d be a GI stage I and with lower GI involvement. Based on her total bilirubin level at 2.7 mg/dL, she’d be a liver stage I. Considering the individual organ stages, translation into an overall grade would be consistent with a grade 2 overall acute graft-versus-host disease.

Given this diagnosis, we initiated therapy with IV [intravenous] steroids at a dose of 1 mg/kg of intravenous methylprednisolone per day. We did give topical steroids for the skin rash as well, with the hope that this initial therapy would provide a response. At the same time, we feared—given the evidence of visceral involvement already in terms of the liver and the diarrhea—that we were seeing the beginning of it, where the snapshot we were getting was not helping us get a glimpse into the actual biology. We feared that our initial steroid dose would not be enough.

This was proven correct; after 3 days, there was no response in terms of her diarrhea or her liver tests. In fact, the diarrhea did progress to reach almost about 1 L a day, and the bilirubin stayed right around 3 mg/dL. Her skin rash did fade a bit and didn’t spread. It turned a bit darker, but it didn’t disappear right away. Because there was no response and things were worsening after 3 days, her steroid dosage was increased to more conventional dosing of 2 mg/kg per day in divided doses of IV methylprednisolone.

Even with the increased steroid dosing, after a total of 7 days of systemic steroids, she still had not experienced a response with her graft-versus-host disease. The diarrhea was now between 1000 and 1500 cc a day, even on bowel rest. Her bilirubin stood around 4 mg/dL. Her skin rash faded and seemed to be resolving. That may have been the only organ that was experiencing any type of response.

At this point, a week into therapy with this course, she certainly met the definition of steroid-refractory acute graft-versus-host disease. She was then started on ruxolitinib 5 mg orally twice a day, which was well tolerated from a subjective, as well as laboratory, point of view. Three days later, we were able to increase to up to 10 mg twice a day.

Transcript edited for clarity.

Case: A 50-Year-Old Woman With Steroid-Refractory Acute Graft Versus Host Disease

Initial Presentation

  • A 50-year-old woman presents on day +32 for a routine follow-up visit after myeloablative matched unrelated donor peripheral blood stem cell transplant for AML.She complains of a new erythematous macular rash and some mildly loose stools which she estimates is 450cc in 24 hours.
  • PMH: unremarkable
  • PE: rash noted on her neck, shoulders, and upper trunk (~60% BSA)

Clinical Work-up

  • Labs: total bilirubin 2.7 mg/dl, AST 60 U/L, ALT 75 U/L
  • Stool testing negative for bacterial/viral infection
  • Negative for HBV, HBV, CMV, EBV, HHV-6
  • Skin biopsy of the rash showed sparse inflammation and abundant dyskeratotic keratinocytes
  • Flexible sigmoidoscopy showed patchy erosion and biopsy showed inflammatory cells with cryptitis
  • She was diagnosed with aGvHD:
    • Skin stage 2
    • GI stage 1
    • Liver stage 1
    • Modified Glucksberg Criteria: grade II; MAGIC Criteria: grade II
  • ECOG 1


  • Admitted as an inpatient for evaluation and initiated methylprednisolone 1.0 mg/kg and topical steroids
  • No treatment response after 3 days, after dose increase of up to 2.0 mg/kg/day IV methylprednisolone
  • After 7 days of systemic steroids diarrhea was around 1500 cc/day, rash was better
  • She was started on ruxolitinib 5 mg PO BID which was tolerated well; increased to 10 mg PO BID 3 days later

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