A 61-Year-Old Man With Graft-Versus-Host Disease

Usama Gergis, MD: A 61-year-old man presented with generalized pruritic rash, abdominal pain, and diarrhea. He had approximately 8 to 12 bowel movements every day, which is equivalent to approximately 1200 to 1600 milliliters per day. The patient underwent haploidentical allogeneic hematopoietic stem cell transplantation for AML [acute myeloid leukemia] approximately 40 days ago.

A review of his laboratory values showed that the patient’s platelet count was 75,000/µL, and his ANC [absolute neutrophil count] was 0.7, so he has neutropenia. He has jaundice, so his bilirubin level of 8 mg/dL and the rest of his LFT [liver function test] results are acceptable. Hepatic viral testing, as well as EBV [Epstein-Barr virus], CMV [cytomegalovirus], and HHV-6 [human herpesvirus 6]test results were all negative. Stool studies were negative. He underwent a flexible sigmoidoscopyand a biopsy. The patient also has lower GI [gastrointestinal] moderate mixed inflammation in the lamina propria and scattered apoptotic bodies without crypt loss, which is a very classic finding for lower GI graft-versus-host disease [GVHD]. A skin punch biopsy showed hyperkeratosis and hypergranulosis associated with lichenoid inflammatory infiltrate. The patient’s graft-versus-host disease was classified as modified Glucksberg criteria grade III and MAGIC criteria grade III.

The treatment is typically systemic corticosteroids—prednisone, 2 mg/kg/day plus topical steroids. After 5 days, there was no treatment response and the patient was appropriately started on ruxolitinib, 5 mg orally twice a day. On day 6, the dose was increased to 10 mg orally twice a day.

This was a very classic case of an older man with AML, which is again approximately the average age for allogeneic transplantation, at least in the United States. The patient underwent haploid identical transplantation and suffers from acute graft-versus-host disease, which affects approximately 40% to 80% of all-comers. Fifty percent of these patients will respond to first-line treatment of high-dose glucocorticosteroids and 50% will not respond. This patient falls in the range of 40% to 80% of individuals suffering from this very common adverse event, and his prognosis will depend very largely on his response. But, if I count all-comers such as this patient—because he did not respond to the first-line treatment and each one trial, the 6-month nonrelapse mortality rate was approximately 50%, and at 1 year, the non-relapse mortality was 60%. Now that the patient has started ruxolitinib, he has a 50% chance of responding to treatment. As far as survival, he has an approximately 50% chance of dying from either graft-versus-host disease or causes other than relapse at 6 months.

Transcript edited for clarity.

Case Overview:

Initial presentation

• A 61-year old man presented with a generalized pruritic rash, abdominal pain and diarrhea (8-12 BMs/day)
• PMH: he underwent haploidentical allogeneic hematopoietic-cell transplantation for AML 40 days ago
• PE: maculopapular erythematous rash on bilateral palms, cheeks, ears and upper back (rash involvement >50% of skin); abdomen is tender to palpation diffusely
  
  

Clinical workup

• Labs: ANC 0.7 x 109/L, plt 75 x 109/L, total bilirubin 8 mg/dl, AST 54 U/L, ALT 60 U/L
  • Negative for HBV, HBV, CMV, EBV, HHV-6
• Negative stool tests
• Flexible sigmoidoscopy with biopsy:
  • Lower GI biopsy showed moderate mixed inflammation in the lamina propria and scattered apoptotic bodies without crypt loss
• Skin punch biopsy of the back shows hyperkeratosis, hypergranulosis associated with lichenoid inflammatory infiltrate
• Modified Glucksberg criteria: grade 3; MAGIC criteria: grade III
  
  

Treatment

• Systemic corticosteroids (prednisone 2 mg/kg/day) + topical steroids (triamcinolone)
  • No treatment response after day 5
• He was started on ruxolitinib 5 mg PO BID, increased to 10 mg PO BID on day 6