A 53-Year-Old Man With Steroid-Refractory Acute Graft-Versus-Host Disease - Episode 1

Case Assessment: 53-Year-Old With Steroid-Refractory Acute GVHD

March 22, 2021
Michael Bishop, MD

Michael Bishop, MD, discusses his concerns for a 53-year-old man diagnosed with acute graft-versus-host disease later deemed as steroid refractory, based on the typical prognosis for patients in similar scenarios.

Michael Bishop, MD: Today we have a case presentation of a 53-year-old man with steroid-refractory acute graft-versus-host disease [GVHD]. The patient had high-risk acute myeloid leukemia. He fortunately achieved a complete remission with standard induction chemotherapy and consolidation with 1 round of high-dose cytarabine, and underwent a matched donor, volunteer donor peripheral blood stem cell transplant.

He presented to clinic day-plus-40 post-transplant. Over the weekend, he had developed a new rash, abdominal pain, and as he described it, countless loose stools for the past 4 days. He had just been seen in clinic that Friday. Over the weekend, this seemed to be getting worse. His past medical history is relatively unremarkable. He did not have any significant other medical problems. On physical examination, he was known to have a relatively diffuse and confluent erythematous rash that primarily involved his arms and upper trunk. It was estimated that the rash involved approximately 45% of his body surface area. When we tried to quantify his stool volume, we were able to demonstrate he was probably having somewhere between 10 and 12 stools per day. Looking at that, that was quantified to be approximately 1100 cc per day.

His laboratory test results from that clinic visit demonstrated that he had a total bilirubin of 2.6 mg/dL. His AST [aspartate aminotransferase] and ALT [alanine transaminase] were 60 U/L and 75 U/L, respectively. His hemoglobin was 9.8 g/dL, but his white blood cell and platelet counts were relatively normal.

He underwent serologies for hepatitis C and hepatitis B, as well as CMV [cytomegalovirus], EBV [Epstein-Barr virus], and HHV-6 [human herpesvirus 6]. All were negative. A stool sample was sent for bacterial and viral infection, including PCR [polymerase chain reaction]. This was negative for any specific viruses, including adenovirus and CMV. Because of the skin rash and the suspicion for graft-versus-host disease, he did undergo a skin biopsy on the arm. The skin biopsy came back the next day and demonstrated he had exocytosed lymphocytes within the skin, and there were dyskeratotic epidermal keratinocytes with follicular involvement. These findings were thought to be consistent with a pathological diagnosis of acute graft-versus-host disease of the skin.

He was referred to GI [a gastroenterologist] and they were able to do a flexible sigmoidoscopy. That demonstrated that he had numerous apoptotic bodies in the crypt epithelium. Again, this was consistent with a pathological diagnosis of graft-versus-host disease of the gut. He underwent staging by organ system for acute graft-versus-host disease. He was staged as stage 2 of the skin, stage 2 of the gut, and stage 1 of the liver, based upon a bilirubin of 2.6 mg/dL. By modified Glucksberg criteria, he was found to have grade 3 disease. He was also thought to be grade 3 using the Mount Sinai Acute GVHD International Consortium criteria. Of significant importance, he had an ECOG performance status of 1, which is important relative to the Glucksberg criteria.

The patient happened to be at day 40. He was already on tacrolimus as part of his graft-versus-host disease prophylaxis. They initiated methylprednisolone at 1 mg/kg and also started with additional topical steroids. After 2 days of treatment, there was absolutely no improvement in either the skin or his stool frequency. The methylprednisolone dose was increased to 2 mg/kg per day. He was continued on this treatment for an additional 5 days, and the rash decreased minimally. There was a decrease in intensity and a slight decrease in extent, but it was still about 25% to 30% of his body surface area.

He was deemed to have steroid-refractory response, not having any response for now over 7 days of treatment at a pretty good steroid dose. He was started on ruxolitinib, given 5 mg orally twice a day, which he tolerated well. He did not have any significant adverse effects, and most importantly, his blood counts stayed stable. Because of that, his dose of ruxolitinib was increased to 10 mg PO BID [orally twice a day] after the third day.

In regard to my initial impression of this case, this is a person who I’m significantly concerned about. He has demonstrated that he has steroid-refractory acute graft-versus-host disease, and this is coming at a time when he’s still on GVHD prophylaxis. The prognosis for this group of patients is not very good. He’s already demonstrated that he’s failed first-line treatment for graft-versus-host disease. The mortality rate tends to be very high, in terms of 50% treatment-related mortality, and that’s primarily due to infection. There’s also a risk for subsequent progression of his disease—going from grade 3 graft-versus-host disease to, potentially, grade 4 graft-versus-host disease.

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