Identifying and Treating Chronic GVHD Early to Minimize Potential Long-Term Negative Outcomes

Clinical Pearl: Early identification of symptoms requires frequent assessment of physical objective and subjective signs. Psychosocial factors are important in accurately diagnosing and treating GVHD in the ambulatory setting. GVHD can continue and worsen in spite of appropriate therapy choices if evaluation and shared decision-making are not a main focus of the therapeutic relationship.

AK is a 28-year-old female with acute myeloid leukemia. She undergoes haploidentical transplant, with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil (MMF) for GVHD prophylaxis. The hematology team stops MMF on day +35. Tacrolimus is titrated at each visit based on lab values and patient presentation; however, the levels are often not therapeutic. After many adjustments, AK reports difficulty adhering to therapy, but the regimen is continued as ordered.

At day +60, AK presents to the AP with symptoms of nausea and vomiting and is admitted to the hospital. She declines endoscopy and is treated with intravenous tacrolimus and methylprednisolone for presumed GVHD. Her symptoms stabilize and she is discharged per her insistence.

On day +85, AK is readmitted to the hospital for recurrent nausea/vomiting and abdominal pain. The AP orders compounded oral budesonide and starts her on corticosteroids 30 mg. She reports continued difficulty taking her tacrolimus as prescribed at home. Her symptoms stabilize, and she is discharged.

Four months posttransplant, AK develops a COVID infection, but no long-term sequelae are noted. Around day +150, she reports dyspnea and shortness of breath (SOB) and presents to the ER. A large pericardial effusion and bilateral pleural effusions are identified on imaging, and AK is treated with antibiotics empirically. No infectious agent is identified. She continues on the GVHD regimen. Her symptoms improve, and she is discharged.

At her post-discharge follow-up visit to the hematology clinic, AK presents with anasarca, painful skin, reduced range of motion, and worsening SOB. The AP also notes diffusely hyperpigmented skin. She is anxious and tearful, imploring the team for an answer and resolution of symptoms. Steroid-refractory GVHD was noted in the past. AK has now developed serositis. She is admitted and placed on solumedrol intravenous 80 mg 2x/day. Oral ruxolitinib 10 mg 2x/day is also started in the hospital.

Within 5 days, AK’s symptoms begin to improve and the steroid taper begins. She transitions to oral prednisone and is discharged 2 weeks after admission to continue ruxolitinib at home.

On day +225, AK reports resolution of SOB. Some dyspnea on exertion is noted, but she is able to complete all activities of daily living. Hyperpigmentation of the skin remains, but erythema is reduced to 20% of body surface area (originally 60%), and the anasarca resolved.

Common Early Presentations of Chronic GVHD and Treatment in Steroid-Dependent Disease

Clinical Pearl: Identifying steroid dependence early in the disease continuum is critical to identifying the need for further intervention and potential mitigation of long-term effects.

PM is a 56-year-old male with angioimmunoblastic T-cell lymphoma. He receives a haploidentical transplant from his brother, with GVHD prophylaxis with sirolimus/tacrolimus. On day +15, he develops intractable nausea and skin rash on his chest and face and is admitted to the hospital. The AP adds prednisone 1 mg/kg/day to his regimen. Within 5 days, the nausea abates and the skin rash improves. The AP reduces the prednisone to 0.5 mg/kg/day, and PM is discharged home.

On day +115, he returns to clinic with reports of abdominal fullness and discomfort. His wife states that his eyes have been “a little yellow.” The rash he experienced in the hospital has returned. This presentation includes tightness in the wrists and around the mouth. Lichen planus is noted at the wrists. The AP notices that he is wearing sunglasses in the exam room. He states that his eyes are irritated by the air conditioning and that they have been watering a lot. His symptoms became noticeable about 2 weeks prior. PM states he didn’t want to call the clinic and alarm anyone, and his wife had been urging him to call. He remains on tacrolimus, and his prednisone dose is reduced to 15 mg daily. Lab results for this visit:

Based on the progression of symptoms while tapering steroids, and the requirement of the dose being > 0.25 mg/kg/day to achieve control of symptoms, PM is diagnosed with steroid-dependent chronic GVHD. The AP increases his prednisone dose to 0.5 mg/kg/day and starts ruxolitinib 10 mg 2x/day. PM is advised to use artificial tears 4x/day.

By day +140, PM has tapered the prednisone to < 0.25 mg/kg/day, and he remains on ruxolitinib 10 mg 2x/day. His liver function tests have stabilized and returned to baseline. He requires the use of artificial tears as needed only. He reports needing the drops once a day on average. PM also has partial resolution of lichen planus on his wrists, and he able to open his mouth completely.