Patient Profile: A 48-Year-Old Man with Chronic GVHD

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EP: 1.Patient Profile: A 48-Year-Old Man with Chronic GVHD

EP: 2.Transplant Conditioning Regimens and GVHD Prophylaxis

EP: 3.Overview of GVHD Types and Symptoms

EP: 4.Therapy Options for Patients with Chronic GVHD

EP: 5.Treatments for Steroid-Refractory Chronic GVHD

EP: 6.Second-Line Approaches to Treating GVHD

EP: 7.Clinical Insights on the Future of GVHD Treatment

Case: A 48-Year-Old Man with Chronic GVHD

• 48-year-old man undergoes myeloablative conditioning followed by matched unrelated donor hematopoietic cell transplant for acute myeloid leukemia w/ tacrolimus + methotrexate as graft versus host disease prophylaxis
  • The donor is a cytomegalovirus seropositive 50-year-old woman with 3 children
• Day +22, acute GvHD of skin emerged, successfully treated with slow steroid taper
• Bone marrow testing performed at 6 months and 12 months post-transplant show AML in complete remission
• 1.5 years post-transplant, new-onset skin changes with hyperpigmentation, lichen-planus and superficial sclerodermatous-like features on lower trunk and lower extremities (not confirmed); 15% BSA involved
• Prednisone initiated, initial dose 0.5 mg/kg/d (max 10 mg/kg per week), then 4-week taper
• After 7 days of prednisone, initial improvement in BSA involvement (now 10% to 15%), with no improvement in range of motion, remained stable thereafter on 0.5 mg/kg every other day

Transcript:

Yi-Bin Chen, MD: Hi, my name is Yi-Bin Chen. I’m the director of the hematopoietic cell transplant and cellular therapy program at Massachusetts General Hospital in Boston. Today I have the pleasure of discussing a case of chronic graft-vs-host disease [GVHD].

We’ll start with a 48-year-old man who undergoes myeloablative conditioning followed by a matched unrelated donor hematopoietic cell transplant for acute myeloid leukemia [AML] in first remission. He receives standard tacrolimus and methotrexate for graft-vs-host disease prevention. His donor is an unrelated donor who is a full match, is cytomegalovirus seropositive, and has had 3 children in the past. The graft source is peripheral blood stem cells. Our patient goes through transplant with the expected off-target toxicities we see, has an uneventful count recovery, and is discharged home.

At his first follow-up visit on day 22, he presents with a skin rash that is consistent with acute graft-vs-host disease, which covers about 80% of his body surface area. The skin rash is consistent with stage III, grade 2 overall acute graft-vs-host disease. He’s treated with systemic corticosteroids and a slow steroid taper. He has a satisfactory response. Bone marrow biopsies performed at 6 months and at 12 months after transplant show that his AML remains in complete remission, and his hematopoiesis is of full donor origin.

About 18 months after transplant, he presents with new onset skin changes: some hyperpigmentation, some lichen planus, and superficial scleroderma-like features on his lower trunk and lower extremities. This involves about 15% to 20% of his body surface area. At this point, systemic prednisone, which has been discontinued for several months, is reinitiated at a dose of 0.5 mg/kg per day. Once a response is achieved after 4 weeks, he’s initiated on a taper. That was the initial plan. After 7 days of systemic prednisone, in a follow-up with the patient, his initial improvement in terms of his body surface area is now down to about 10% to 15% from what was previously 15% to 20%. He has no improvement in his range of motion, which wasn’t hugely limited at presentation, but certainly was not full. Therefore, he remains stable on 0.5 mg/kg every other day of prednisone.

In looking at this case, we have to acknowledge and understand that allogeneic transplantation is always undertaken for curative potential these days. With every reasonably young and healthy patient with acute myeloid leukemia, we think about if we can proceed to allogeneic transplantation as a consolidative therapy. With the advent of reduced intensity and improvements in supportive care, we’ve been able to expand our patient upper age limit as well as accept certain comorbidities. But we do think about risks, benefits, and overall prognosis. The calculation is sort of 2 calculations. One is based on the biology of the underlying disease. What are the chances we can achieve a durable remission or “cure” with allogeneic transplant? The other calculation is, what is the risk? Ultimately that can be best summarized by nonrelapse or transplant-related mortality. The ultimate risk is death from complications. But even before that, there is morbidity that can happen from transplant-associated complications.

For this patient, we know he has acute myeloid leukemia in first remission, and he’s undergoing a myeloablative allogeneic transplant. Based on the heterogeneity of AML, I think his prognosis can range anywhere from a 20% to 25% chance of durable remission for AML with high biological risk features such as complex karyotype with a concurrent TP53 mutation, to as high as possibly 70% to 75% if he has standard risk that is minimal residual disease negative by high sensitivity molecular diagnostics, or even those with what we believe to be a FLT3-ITD mutation, where we can add FLT3 tyrosine kinase inhibitor maintenance afterward. His long-term durable remission from his AML varies depending on the underlying biology. In terms of his overall risk from transplant, for a myeloablative conditioning for this type of patient who’s 48 years old, we’d likely use myeloablative busulfan and fludarabine. We’d probably quote somewhere around a 10% risk of 2-year transplant-related mortality. Overall, the characteristics of his disease would dictate the tenor of the conversation about prognosis.

In terms of thinking about the modern indications for transplant, most of our patients undergoing allogeneic transplant have a hematological malignancy, though the specific hematological malignancy has changed throughout the years. This field was built on performing matched sibling transplants for chronic myeloid leukemia in chronic phase, and it’s rare these days if we transplant 1 or 2 patients with chronic myeloid leukemia annually at our center. In 2023, our most common indications are myeloid malignancies. That includes acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, and acute lymphoid leukemia would come in after that. The other diagnoses are far less common. The incidence of transplant for non-Hodgkin lymphoma and Hodgkin lymphoma has certainly decreased with the advent of other therapies as well.

In terms of graft sources for transplant, improvements in platforms, supportive care, and graft-vs-host disease prophylactic regimens have allowed us to expand the donor options as well as graft sources. In terms of the actual sources, we’re able to use conventional bone marrow, which has decreased in numbers recently. A lot of that has been driven by pandemic-related dynamics and the ability to secure and guarantee fresh bone marrow. Peripheral blood stem cells, or peripheral blood progenitor cells, mobilized by GCSF [granulocyte colony-stimulating factor] and collected by apheresis remains the most common graft source from related or unrelated donors. We are able to use umbilical cord blood. The incidence of using umbilical cord blood has decreased over the years as well, with the rise of the ability to use either haploidentical, or mismatched-related transplants, as well as mismatched-unrelated donors.

Transcript edited for clarity.