The article provides a comprehensive review of graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic cell transplantation (HCT). It discusses the etiology, clinical features, pathophysiology, prevention, and treatment of GVHD. Key points include: 1. **Etiology and Clinical Features**: GVHD occurs when donor T cells respond to genetically defined proteins on host cells, primarily Human Leukocyte Antigens (HLA). The incidence of acute GVHD is related to the degree of HLA mismatch between donor and recipient. Clinical manifestations include skin, gastrointestinal, and liver involvement. 2. **Pathophysiology**: GVHD involves three phases: activation of antigen-presenting cells (APCs), activation and proliferation of donor T cells, and destruction of target tissues by cellular and inflammatory mediators. APCs produce "danger" signals that activate donor T cells, which then cause tissue damage. 3. **Prevention**: Strategies include T cell depletion (TCD), use of anti-T cell antibodies, and pharmacological manipulation of T cells. Reduced-intensity conditioning (RIC) regimens reduce the incidence of severe GVHD but may delay the onset of acute GVHD. 4. **Treatment**: Steroids are the standard treatment for GVHD, but extracorporeal photopheresis (ECP) and blockade of inflammatory cytokines like TNF-α are also effective. Chronic GVHD is treated with immunosuppressants, but responses are unpredictable and toxicities are common. 5. **Supportive Care**: Meticulous supportive care is crucial due to the extended duration of immunosuppressive treatments and multiple medications. This includes infectious prophylaxis, management of infections, and monitoring for toxicities associated with immunosuppressants. 6. **Future Directions**: As allogeneic transplantation becomes more common, novel approaches to GVHD are needed. Identification of biomarkers and the use of cellular component therapy, such as regulatory T cells, may improve outcomes. The article emphasizes the importance of collaboration between hematologists and transplant specialists in managing GVHD and its complications.The article provides a comprehensive review of graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic cell transplantation (HCT). It discusses the etiology, clinical features, pathophysiology, prevention, and treatment of GVHD. Key points include: 1. **Etiology and Clinical Features**: GVHD occurs when donor T cells respond to genetically defined proteins on host cells, primarily Human Leukocyte Antigens (HLA). The incidence of acute GVHD is related to the degree of HLA mismatch between donor and recipient. Clinical manifestations include skin, gastrointestinal, and liver involvement. 2. **Pathophysiology**: GVHD involves three phases: activation of antigen-presenting cells (APCs), activation and proliferation of donor T cells, and destruction of target tissues by cellular and inflammatory mediators. APCs produce "danger" signals that activate donor T cells, which then cause tissue damage. 3. **Prevention**: Strategies include T cell depletion (TCD), use of anti-T cell antibodies, and pharmacological manipulation of T cells. Reduced-intensity conditioning (RIC) regimens reduce the incidence of severe GVHD but may delay the onset of acute GVHD. 4. **Treatment**: Steroids are the standard treatment for GVHD, but extracorporeal photopheresis (ECP) and blockade of inflammatory cytokines like TNF-α are also effective. Chronic GVHD is treated with immunosuppressants, but responses are unpredictable and toxicities are common. 5. **Supportive Care**: Meticulous supportive care is crucial due to the extended duration of immunosuppressive treatments and multiple medications. This includes infectious prophylaxis, management of infections, and monitoring for toxicities associated with immunosuppressants. 6. **Future Directions**: As allogeneic transplantation becomes more common, novel approaches to GVHD are needed. Identification of biomarkers and the use of cellular component therapy, such as regulatory T cells, may improve outcomes. The article emphasizes the importance of collaboration between hematologists and transplant specialists in managing GVHD and its complications.