Bonnie J. Dirr, APRN:Let’s continue on with CB’s (example patient) case and go over a few more highlights. CB proceeded with his match related stem cell transplant, as we previously noted, with cyclophosphamide and TBI [total body irradiation] as part of his conditioning and [tacrolimus] and methotrexate as part of his GVHD [graft-vs-host disease] prophylaxis. We previously highlighted his prior comorbidities and, to note, he was also previously on the dasatinib and treated with blinatumomab. He began his cyclophosphamide on days -5 through -4 and his TBI conditioning was on day -3 through day -1. Those were all delivered prior to his actual stem cell transplant. Unfortunately, he did develop moderate mucositis requiring dexamethasone and a dose reduction of his methotrexate on day 11, given half dose, secondary to his increased secretions and respiratory symptoms. He did require pain management with a PCA [patient-controlled analgesia), although he did [experience] resolved improvement with his interventions. By day +13 he was transitioning back to pos [per os/by mouth, taking in liquids and solids, and otherwise, his nausea was managed with ondansetron and olanzapine. G-CSF [granulocyte colony-stimulating factor] was started on day +12 and his counts recovered quickly, and he became nonneutropenic by day +13. He was maintained, as we previously have noted, on acyclovir…trimethoprim as his ID prophylaxis, and he was continued on that regimen with quick count recovery. He was monitored weekly for viral and fungal infections, including CMV [cytomegalovirus], EBV [Epstein–Barr virus], beta-glucan, and galantamine. He received ursodiol for his hepatic veno-occlusive disease prophylaxis. His GI [gastrointestinal] decontamination was maintained with neomycin [and] polymyxin. Mouth care consisted of chlorhexidine, nystatin, and stannous fluoride. His GVHD prophylaxis, as we noted, was on days -3, and his methotrexate was started on day +1 through +11, and we already highlighted his dose reduction on day +11. Otherwise, the only notable remarkable factor was that he did develop some hypertension and…amlodipine [was] added. But his blood pressure briskly responded, and he was able to prepare for discharge pretty quickly. Dr Gooptu, this patient came in to see you on day +19 in the ambulatory clinic and unfortunately had a new rash on bilateral forearms, upper chest, and neck with a very quick onset within 24 hours. He did have resolving mucositis [and] hoarseness since his hospitalization. He had no progressive URI [upper respiratory infection] symptoms, no chest or nasal congestion. Eating and drinking well, as previously noted, reasonable energy and able to keep up with his ADLs [activities of daily living]. He was afebrile and he had no chills. His liver function tests were unremarkable, and the remaining labs also were denoted for no other remarkable changes. Review of systems otherwise for him was negative. The treatment interventions for CB: His prophylaxis was maintained [through] tacrolimus and methotrexate. His drug level was a little bit low on his current dose of 2.5 mg BID [two times a day], and those titrated up to 2.5 mg and 3 mg. Clearly at this point, he had had grade 2 of his skin and grade 1 overall of acute graft-vs-host disease [presenting on] upper arms, chest, back, and neck. Steroids were initiated at 1.5 mg/kg. The dose was rounded down secondary to the BMI [body mass index] to 100 mg per day. The patient was provided with education and started on the oral steroids. In the setting of the steroid burden, isoconazole was added to his ID prophylaxis, which we’ve previously discussed. We can see here that CB’s presentation of his acute GVHD appeared to be fairly rapid with his onset. Dr Gooptu, can you please discuss with us what presentations and symptoms are observed in patients with acute graft-vs-host disease, and do they all have a rapid onset such as in the case with CB?

Mahasweta Gooptu, MD: Acute GVHD, of course, is one of the most [detrimental] complications of stem cell transplantation, the allogeneic transplantation, and typically will present with a constellation of symptoms: diarrhea, rash, liver function abnormalities, hyperbilirubinemia, and transaminitis. The rash is typically a macular purpura erythematous rash, classically sometimes involving the palms and soles, and can involve various degrees of body surface area. In more severe cases, you can see an erythroderma [INAUDIBLE] in the most severe cases. Diarrhea is typically loose, watery stools multiple times a day with abdominal cramping, significant dehydration, and loss of protein through the day [via] stools. Finally, the liver function abnormalities, the way we grade acute GVHD with liver involvement, is by looking at the degree of hyperbilirubinemia. But you can also see elevations in alkaline phosphatase and transaminitis. These are the typical symptoms. I would say that onset can range from acute to slightly subacute but typically would be in days to maximum 1 to 2 weeks. Quite different from the chronic form of graft-vs-host disease, which is a much more insidious process. I would say CB’s presentation was pretty classic for acute skin GVHD.

Bonnie J. Dirr, APRN: Dr Gooptu, can you please explain to us how a diagnosis of acute graft-vs-host disease is made for your patients? [For] example, with CB, were there particular criteria in diagnosing his skin? We see that Dr Inyang is a very collaborative partner for us here at Dana-Farber. What other teams are involved in other subspecialties in caring for the transplant patient? Do you ever reach out to other disciplines such as dermatology in helping you make the diagnosis of graft-vs-host disease?

Mahasweta Gooptu, MD: That’s a great question. The acute GVHD is a clinical diagnosis at the outset and can be confirmed with various histopathologic tests. Because of the acuteness of presentation, we sometimes have to institute treatment based on clinical presentation before we even have results from any kind of diagnostic procedure. Having said that, we do look for the classical pattern of the rash, which is, as I said, macular purpura erythematous rash; we look for involvement of the palms and soles. We also try to exclude other factors which could cause such a rash, which is typically drugs. It is sometimes difficult to distinguish between a drug rash and an acute GVHD rash. If we really have a diagnostic dilemma, we will involve our dermatology colleagues, who also work very closely with us, and they can do a skin biopsy. That can often tell you that this is definitively acute GVHD, although again, sometimes [it is] difficult to distinguish between a drug rash and acute GVHD on pathology. Similarly, if you have a classic presentation of gut GVHD, you often will institute treatment right away but always try to confirm it with a colonoscopy or flexible sigmoidoscopy with biopsies, which can be diagnostic. Similarly, we can do liver biopsies, so we do work closely with our GI and [dermatology] colleagues in workup of GVHD. But I will say that the majority of patients who present with classical symptoms in the clinic will get treated even without a skin biopsy.

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