Signs and Symptoms of Acute and Chronic GVHD

EP: 1.Graft versus Host Disease Background

EP: 2.Overview of GVHD Risk Factors

EP: 3.Current GVHD Prophylaxis Strategies

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EP: 4.Signs and Symptoms of Acute and Chronic GVHD

EP: 5.Statistics on the Incidence of Chronic GVHD

EP: 6.Identification of Patients at High Risk for GVHD

EP: 7.Assessment of Chronic GVHD Symptoms

EP: 8.The NIH Clinical Scoring of Organ Systems

EP: 9.The Chronic GVHD Treatment Paradigm

EP: 10.Patient Case: A 48-Year-Old Man with Chronic GVHD

EP: 11.Treatment Goals for a Patient With Chronic GVHD

EP: 12.Steroid-Refractory Chronic GVHD Background

EP: 13.Therapy Options for Steroid-Refractory Chronic GVHD

EP: 14.Ibrutinib as Second-Line Therapy for Steroid-Refractory Chronic GVHD

EP: 15.The iNTEGRATE Trial: Ibrutinib With Prednisone as First-Line Therapy for cGVHD

EP: 16.The REACH3 Clinical Trial of Ruxolitinib in Chronic GVHD

EP: 17.Clinical Experience with Ruxolitinib for cGVHD

EP: 18.The ROCKstar Study of Belumosudil in cGVHD

EP: 19.Real-World Experience with Belumosudil

EP: 20.Summary of Axatilimab for cGVHD

EP: 21.Therapy Selection for Patients with Chronic GVHD

EP: 22.Discussion of Long-Term Effects of GVHD Therapy

EP: 23.Future Directions in Graft Versus Host Disease

Transcript:

Yi-Bin Chen, MD: The timing of graft-vs-host disease [GVHD] has shifted throughout the years. A lot of that is due to the advances we’ve talked about and the differences in immune reconstitution of the different grafts and platforms we use. This is how we view graft-vs-host [disease]: acute is broken up into classic and late. Classic is before day 100, and you can see the peak there from when it happens. If it happens after day 100, it’s still called acute based on clinical manifestations, but it’s classified as late. If a patient has clinical features of both acute and chronic, we call them an overlap patient. That definition has changed throughout the years.

You can see the timeline of chronic graft-vs-host disease, the manifestations of such, and when they happen. All of us taking care of many patients throughout the years, we can all say that none of our patients is ever at 0 risk for developing chronic graft-vs-host disease. That’s why there isn’t a great plateau on that curve for chronic. Any trigger in inflammation—an infection or something else—always seems to trigger some manifestation of chronic graft-vs-host disease. That’s why it’s become a huge focus of what we do in terms of prevention treatment, as well as other ways to improve the lives of patients surviving transplant. I’d like to touch on the clinical manifestations. Colleen, do you want to review the major manifestations of acute GVHD and then chronic as well?

Colleen Danielson, NP: When we’re seeing patients in clinic, we’re assessing for signs and symptoms of graft-vs-host disease, knowing that in the acute phase skin, the GI [gastrointestinal] tract and the liver can be involved. We’re looking for any rash in the skin or itching, any diarrhea, nausea, or vomiting. Any abdominal pain, cramping, and any jaundice that we see. There are potentially more organs that could be involved with chronic graft-vs-host disease. Obviously this list is a bit longer. Still, the skin could be involved. We’re assessing for rash and or itching with chronic GVHD but also any changes to the skin in terms of tightening or a luxury feeling to the skin or swelling. We’re assessing the mouth for dry mouth, pain, sensitivity and the eye for dryness or gritty feeling. We want to assess for the GI tract—specifically esophageal—involvement that could potentially lead to dysphasia or difficulty with swallowing, particularly food and pills. Is there any fatigue that patients are experiencing? Muscle symptoms are important to assess for muscle weakness, cramping, or pain, and decreased range of motion to the joints. We also want to assess for any genital involvement—dryness, itchiness, or pain.

Yi-Bin Chen, MD: When we assess for graft-vs-host disease, it often takes a while if you’re going to ask all these questions. Also, these aren’t specific. It’s our job as clinical providers to work with the patient to differentiate what’s what in trying to figure this out. Colleen already reviewed the most typical presentations. I’d like to ask a question to Corey and Catherine, because this will be somewhat impacted by the institution you work at. Corey, what’s your feeling on upper GI graft-vs-host disease? Does it exist? Does it matter?

Corey Cutler, MD, MPH, FRCPC: It’s a little of an East Coast–vs–West Coast issue. Certainly, it exists. If you do upper GI biopsies for individuals, you can see things like crypto apoptosis and loss of the architectural structure of the upper GI tract. That probably represents acute graft-vs-host disease, although one has to be careful because conditioning-related injury could appear very similar. On the other hand, the second part of your question was, does it matter? To address that, we performed a large retrospective analysis of the CIBMTR [Center for International Blood & Marrow Transplant Research] data set looking at the additive value of upper GI GVHD in terms of influencing prognosis. We were able to demonstrate quite clearly in a very large data set that adding upper GI GVHD doesn’t change the prognostic score of whatever stage the patient would have been in, in the absence of upper GI GVHD. It’s important to take care of the patient and address their symptoms, which might be nausea and feeling bloated and unable to eat with anorexia, but that doesn’t change the long-term prognosis of acute graft-vs-host disease.

Yi-Bin Chen, MD: We would share in that, being across town from you. I feel that there are upper GI GVHD issues. We have to look very hard to find the real cases that require the same dose that we treat other patients at. Catherine, you’ve moved to an institution that’s known to be very aggressive in identifying upper GI GVHD. What are your thoughts on it?

Catherine J. Lee, MD, MS: I agree with Dr Cutler. Clinically, I’ve seen multiple patients who express symptoms of nausea, bloating, and anorexia. At Hutch [Fred Hutchinson Cancer Center] early preemptive treatment is initiated. It’s very common. It could be a very short course of steroids, 2 to 4 weeks. We see symptoms improve remarkably. This may be done without actual tissue biopsy. It’s treated based on symptoms. In the acute setting, it’s difficult to differentiate between toxicity from therapy, but clinically we see that giving corticosteroids can help patients improve.

Yi-Bin Chen, MD: As Colleen will attest, we probably couldn’t get the number of endoscopies we would need to be aggressive about diagnosing our patients. A short course of steroids is part of care for a good number of patients, to get them through that period.

Transcript edited for clarity.