A 49-Year-Old Man With Steroid-Refractory Chronic Graft Versus Host Disease - Episode 1

Case Overview: 49-Year-Old Man With Chronic GvHD

Corey S. Cutler, MD, MPH, FRCPC: Today I’ll be presenting a case of chronic graft-versus-host disease [GvHD]. The case is of a 49-year-old man who underwent a matched, related allogeneic stem cell transplant from his brother approximately 9 months prior to this presentation. He was previously well and healthy and had no other major medical problems. He received standard tacrolimus and methotrexate as his primary GvHD prophylaxis. He presents to the clinic with complaints of a change in the color and the texture of his skin, some issues with his nail beds, and some oral sensitivity to spicy and hot foods. He also notes that he had elbow and shoulder discomfort and was having trouble raising his arms to perform his activities of daily living, such as brushing his hair.

Upon physical examination, he has some deep pigmentation changes over his face and has lichen planus-like features as well over his chin, nose, cheeks, as well as his shoulder girdle, and his forearms. On the inside of his mouth, he’s got some erythema. There’s longitudinal ridging of the fingernails, and he has joint stiffness as well as a decreased range of motion. When we examine him even closer, he has a photographic range of motion score of 4, and his laboratory evaluation reveals a platelet count of 70,000 µL with a normal hematocrit and a normal white blood cell count. His total serum bilirubin is 7.6 mg/dL with elevated transaminases, an AST [aspartate aminotransferase] of 150 U/L, an ALT [alanine transaminase] of 165 IU/L, and an alkaline phosphatase of 430 IU/L. His performance status is an ECOG [Eastern Cooperative Oncology Group] performance score of 1, and overall he is given an NIH [National Institutes of Health] global severity score of moderate chronic GvHD based on the number of organs he has involved.

First, I’ll describe the initial presentation and the prognosis. He has NIH moderate chronic graft-versus-host-disease, and there are a couple of ways of trying to prognosticate how he’s going to do with therapy and over time. The main prognostic scoring system was published by Mukta Arora, MD, MBBS, MS, and colleagues in Blood in 2011 and looks at a number of clinical factors that we could use to generate a risk score. These factors include the age of the patient at the time of transplantation, the presence of prior acute graft-versus-host disease, the time from transplantation to the presentation of chronic graft-versus-host disease, his serum bilirubin. His total platelet count is important, his performance status, and then some factors about his transplant itself—the type of GvHD regimen he received, whether he received a sex mismatched or matched transplant, and who his donor type was.

Taking all of these factors into consideration, he gets an overall risk score of 5 points with a maximum of well over 10. That corresponds to risk group 2 and corresponds to non-relapse mortality of about 20% at 5 years from the time of initial presentation, and an overall survival of about 67%. This is the most commonly used way we can gauge prognosis from the time of diagnosis of chronic graft-versus-host disease.

The patient we have been discussing unfortunately had no response to corticosteroids after 4 weeks at a dose of 0.5 mg/kg/day. The treating physician decided to add ruxolitinib at that point at a dose of 5 mg twice a day and escalate it up to 10 mg twice a day. I will mention that this is off-label use of ruxolitinib, but it is a fairly standard practice among my colleagues. The nice thing about ruxolitinib is that when subjects do respond to it, generally responses are fairly rapid, so one tends to know that a patient is going to respond or not within 2 to 3 weeks. It is one of the advantages of this compound that one gets to decide early on whether we’re going to pursue this in the long term.

Typically what we would see is that oral sensitivity would go down, and skin rashes will start to fade. They may be changing from lichenoid or erythematosus changes to a brownish, hyperpigmented type of discoloration, suggesting that inflammation was going down. The bilirubin hopefully would start to go down as well rather quickly. I think for this patient the most ominous sign of their chronic GvHD is in fact the hyperbilirubinemia. Joints are difficult to get to respond quickly.

There is often an element of fasciitis or sclerosis around the joint space, so sometimes it’s a mixture of fascial and actual joint involvement. That type of change does take time to reverse, and I wouldn’t necessarily change therapy if the joints were not improving very rapidly. I would look to organs such as the mouth and the inflammatory skin changes to make a decision on early change off of ruxolitinib if in fact it wasn’t working. The liver would probably be the strongest signal for us to decide whether ruxolitinib was working.

Transcript edited for clarity.


Case: A 49-Year-Old Man With Steroid-Refractory Chronic Graft Versus Host Disease

Initial presentation

  • A 49-year-old man complains of “color and texture” changes to his skin, nails and the inside of his mouth; he also complains of shoulder and elbow joint discomfort limiting his normal daily activity
  • PMH: he underwent matched related allogenic transplant from his brother for treatment of AML
  • PE: depigmentation and lichen planus-like features noted on his chin, nose, cheeks and forearms bilaterally, and in the oral mucosa (~40% BSA); longitudinal ridging of the fingernails; joint stiffness and decreased range of motion

Clinical workup

  • Labs: plt 70 x 109/L, total bilirubin 7.6 mg/dl, AST 150 U/L, ALT 165 U/L, ALP 430 U/L
    • Negative for HBV, HBV, CMV, EBV, HHV-6
  • NIH Global Severity of cGvHD moderate cGvHD; P-ROM score 4
  • ECOG 1

Treatment

  • Tacrolimus + dexamethasone oral rinse
    • No treatment response after 4 weeks
  • He was started on ruxolitinib 5 mg PO BID which was tolerated well; increased to 10 mg PO BID on day 6