graftversushost

Graft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplantation in which donor immune cells attack the recipient's tissues. While GVHD is a major complication, donor immune cells can also mediate a beneficial graft-versus-leukemia effect by targeting residual malignant cells.

GVHD results when donor T cells recognize host alloantigens as foreign. In acute GVHD, inflammation is driven by T cells and antigen-presenting cells in the skin, liver, and gut, often within the first 100 days after transplant. Chronic GVHD is a more complex process involving alloimmune responses and tissue remodeling that can resemble autoimmune disease.

Acute GVHD presents with a characteristic skin rash (often maculopapular or erythrodermic), elevated liver enzymes and bilirubin, and diarrhea or ileus due to GI involvement. Chronic GVHD can cause dry eyes and mouth, lichen- or scleroderma-like skin changes, hepatic dysfunction, and GI symptoms.

Key risk factors include HLA mismatch, multiple-locus mismatch, older recipients, female donors to male recipients, high-intensity conditioning, and insufficient GVHD prophylaxis. Prophylaxis usually combines a calcineurin inhibitor (cyclosporine or tacrolimus) with methotrexate or mycophenolate mofetil, with strategies such as post-transplant cyclophosphamide used for haploidentical transplants to reduce risk.

Treatment of acute GVHD typically starts with systemic corticosteroids (e.g., prednisone 1–2 mg/kg/day). If steroid-refractory, second-line therapies include ruxolitinib, extracorporeal photopheresis, and other immunosuppressants. Supportive care targets infection prevention and organ support.

GVHD remains a major cause of non-relapse mortality after allo-HSCT. Outcomes vary with organ involvement and response to therapy, and chronic GVHD can require long-term immunosuppression and multidisciplinary care.