Bonnie J. Dirr, APRN: Getting back to the case with CB [patient case study], he did receive a wonderful response in terms of the oral steroids that were added to his tacrolimus immunosuppression. He was actually able to taper off steroids by day +90 in the management of his acute GVHD [graft-vs-host disease]. He had been transitioned back to dasatinib 70 mg po qd (one pill, by mouth, once each day) in the setting of his posttransplant maintenance for his PH+ ALL (Philadelphia chromosome-positive acute lymphoblastic leukemia). The 100-day staging bone marrow biopsy was free of disease, and thus tacrolimus taper was initiated, and he was smoothly tapered off by day +188. He returned to the clinic for a routine visit on day +240. Unfortunately, CB had developed scattered, dry, scaly patches on bilateral lower extremities. The skin fascia was tight, and it was causing him significant impeding of his mobility. He had ocular symptoms with morning secretions that he noted with thick crusting, dry eyes that had a quick progression. The treatment interventions at the time that were added—[he was] restarted on prednisone at 0.5 mg/kg with a total dose of 60 mg. His tacrolimus was restarted at 0.5 mg once a day, and cyclosporine drops in preservative-free re-wetting drops were also added for his ocular symptoms. ID prophylaxis, as we have highlighted before, was his acyclovir…trimethoprim, and isoconazole was added back as an antifungal agent in the setting of the steroid burden. As he proceeded on in his journey, on day +281, he developed moderate chronic skin and fascia changes to bilateral lower extremities. He did have some improvement of his ocular symptoms. In terms of his steroids, it was thought to be that was causing the response to his oral symptoms—the addition of the oral steroids. His skin was still bound down. Thus ruxolitinib, 5 mg po bid [medication taken by mouth, or orally] was added to his steroids, although, as we noted, his steroids were able to be tapered down to 50 mg a day, as they were not making much of a difference with his skin. His tacrolimus was increased to 0.5 mg twice a day, and his remaining therapies continued. He was referred to [Massachusetts] Eye and Ear Infirmary to our colleagues for assessment and management for his ocular GVHD. Dr Gooptu, we’ve seen the evolution of CB’s journey. He returned to clinic several weeks later following the taper of his immunosuppression of tacrolimus, and he exhibited what appeared to be chronic graft-vs-host disease symptoms. Can you please provide us an overview of chronic graft-vs-host disease, and generally, which systemic body parts are mainly affected by chronic graft-vs-host disease?

Mahasweta Gooptu, MD: Chronic graft-vs-host disease is a very different entity from the acute form of graft-vs-host disease. The one commonality is that both are mediated by the donor allograft. Chronic GVHD is a significant quality-of-life issue for transplant survivors and one of the issues which really increases morbidity long term. We are very focused on preventing and treating chronic graft-vs-host disease. [This disease] can affect various organ systems. Typically, if you divide it into 4 large groups, you go cutaneous, which could be ocular, oral, or even vaginal, and the GI tract. Skin and myofascial [symptoms], some of which CB developed; the lungs can be affected, which is a very severe form of chronic GVHD, which we call bronchiolitis obliterans. Then there are a basket group of others where you can have some nonspecific symptoms, which I think we learn with every patient but are clearly part of chronic GVHD. The manifestations can be somewhat protean, and it really takes practice time and a lot of experience to pick up on these symptoms. The patients themselves will often not notice the symptoms right away or just think they are nonspecific aches and pains [such as] ocular irritation. “Oh, I can’t tolerate spicy food.” They don’t always recognize that these are the first signs of chronic graft-vs-host disease. They may not even report it until they come to see you for a follow-up visit. In [CB’s] case, I think the presentation was quite classic. For particular organ systems such as the eye or the mouth, we do involve our ophthalmology and oral medicine colleagues, some of whom are specialized in the management of chronic GVHD, and there are specific diagnostic tests as well which have to be done. But again, it’s mainly a clinical diagnosis.

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