A 50-Year-Old Woman With Steroid-Refractory Acute Graft Versus Host Disease - Episode 2

Predictive Prognosis and Risk-Stratification in aGvHD

March 12, 2021
Yi-Bin Chen, MD

Yi-Bin Chen, MD, gives insight into the current accuracy of predictive prognostics and the potential use of biomarkers to risk stratify patients with acute GvHD in the future.

Yi-Bin Chen, MD: Even though she was only overall grade 2, we feared that she had much more aggressive disease, given we were already seeing visceral involvement of her liver and lower GI [gastrointestinal] tract. Specifically, the lower GI disease is the most difficult organ to treat. If she hadn’t come that day and instead saw you 2 days later when the stool was maybe 1100 cc a day, her grade would have automatically been much worse, and you might think of her differently. That’s why you have to consider the perspective of when you’re seeing the patient and what the actual biology is.

Given the snapshot, we don’t have a measure of the biology of her disease to accurately predict the prognosis. Although the clinical grade does loosely correlate with prognosis, it is not a very good predictor. What we lack is something like noninvasive biomarkers that can accurately predict the prognosis of our patient. More importantly, we can have risk-stratified treatments for the different groups.

There are biomarkers that are commercially available and developed by MAGIC [Mount Sinai Acute GVHD International Consortium]. These measure 2 proteins called REG3-alpha and ST2, which are thought to be measures of mucosal injury in the bowel. They have been shown to predict for prognosis, but we don’t have proof that risk stratifying our treatments based on these biomarkers helps our patients. We have no proof that we should treat any of these patients differently based on their biomarker group. Future clinical trials and efforts can help us better accurately prognosticate patients, so we can develop these risk-stratified treatments.

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

Treatment

  • 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