Consensus conference on clinical practice in chronic graft. Graftversushost disease is a condition in which donor cells think the recipients cells are foreign and attack them. However, graft versus host disease gvhd remains a potential source of nonrelapse morbidity and mortality for these patients. Acute graft versus host disease agvhd remains the second leading cause of death. Conditioning regimen cause profound damage to the host tissues leading to release of inflammatory cytokines like tumor necrosis factor and interleukin1. The pathophysiology of acute gvhd is complex and can be conceptualized to be a threestep process based on murine studies. Despite considerable advances in our understanding of the pathophysiology of graft versus host disease gvhd, its prediction remains unresolved and depends mainly on clinical data. Preclinical model systems in patients undergoing allogeneic hsct have enriched our understanding of pathophysiology of gvhd and led to the development of immunosuppressive prophylaxis for gvhd. Pdf the pathophysiology of acute graftversushost disease. The pathophysiology of chronic gvhd is poorly understood because of the lack of highly satisfactory animal models and basic studies. Acute graft versus host disease mukta arora md msmukta arora md. Graft versus host disease gvhd is a complication that can develop after a person has had a bone marrow or stem cell transplant. Ferrara abstract the pathogenesis of acute graft versus host disease gvhd is multistep process. Gvhd can be considered an exaggerated, undesirable manifestation of a normal inflammatory mechanism, in which donor lymphocytes encounter foreign.
Directions to hospitals treating type page name here. Pathophysiology of acute graftversushost disease gvhd. Graftversushost disease gvhd is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation hsct. Acute graftversushost disease gvhd occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. The therapeutic potential of hematopoietic cell transplantation hct for the treatment of malignant disease relies on graftversusleukemia gvl or graftversustumor gvt responses to eradicate residual tumor cells via immunological mechanisms. Treatment of graftversushost disease in human allogeneic marrow graft recipients. Pathogenesis and therapy of graftversushost disease. Chronic graftversushost disease cgvhd remains the major cause of morbidity and nonrelapse mortality after allogeneic hematopoietic stem cell transplantation sct.
Risk factors for the development of acute gvhd include human leukocyte antigen hla disparity, increasing age of the recipient, donor and recipient gender disparity particularly a multiparous female donor with a male recipient, type and status of underlying disease, transplant conditioning regimen intensity, abo compatibility, performance score, whiteblack race, cytomegalovirus. However, graft versus host disease gvhd remains the most frequent and serious complication following allogeneic hct and limits the broader application of this. Pathophysiology of chronic graftversushost disease and. Gvhd can be considered an exaggerated, undesirable manifestation of a normal inflammatory mechanism, in which donor lymphocytes encounter foreign antigens in a milieu that fosters inflammation. Pathophysiology of acute graft versus host disease. Advances in graftversushost disease biology and therapy. Depending on the time at which it occurs after hct, gvhd can be either acute or chronic47. Pathophysiology the pathophysiology of acute gvhd is. Furthermore, in the thymic medulla, singlepositive t cells will encounter marrowderived apcs also bearing. Graftversushost disease james l m ferrara, john e levine, pavan reddy, ernst holler haemopoieticcell transplantation hct is an intensive therapy used to treat highrisk haematological malignant disorders and other lifethreatening haematological and genetic diseases.
In the context of the clinical history, the morphologic findings are compatible with graft versus host disease add differential diagnoses if applicable. Graft versus host disease gvhd usually follows bone marrow transplantation. Treatment of established human graftversushost disease by antithymocyte globulin. Pathophysiology, prevention, and treatment of acute graftversushost disease abhinav deol, voravit ratanatharathorn, joseph p ubertidepartment of oncology, blood and marrow stem cell transplant program, barbara ann karmanos cancer institute, wayne state university school of medicine, detroit, mi, usaabstract. Review article from the new england journal of medicine pathophysiology of chronic graftversushost disease and therapeutic targets. Complications of allogeneic hematopoietic stem cell transplantation hsct remain barriers to its wider application for a variety of diseases. Pdf pathophysiology of acute graftversushost disease pavan reddy academia. Since the discovery of sickle cell disease scd in 1910, enormous strides have been made in the elucidation of the pathogenesis of its protean complications, which has inspired recent advances in targeted molecular therapies. When t cells from a bone marrow donor begin to attack the host within 3 months after hematopoieticcell transplantation, acute graftversushost disease results. Graftversushost disease gvhd has been the primary limitation to the wider application of allogeneic bone marrow transplantation bmt. In step 1, the conditioning regimen leads to the damage and. Pathophysiology of acute graftversushost disease pavan reddy department of internal medicine, university of michigan comprehensive cancer center, ann arbor, mi, usa summary graftversushost disease gvhd has been the primary limitation to the wider application of allogeneic bone marrow transplantation bmt. Graft versus host disease gvhd is an immune mediated disease due to complex interaction between donor lymphoid tissue and recipients immunity occurring after transplantation. The role of calcineurin inhibitors remains controversial, especially in patients with low risk for mortality normal platelets counts, whereas patients.
The pathophysiology of acute gvhd is complex and can be conceptualized to be a three. The disease usually appears after day 100 and is characterized by signs and symptoms similar to autoimmune diseases. Gvhd also applies to other forms of transplanted tissues such as solid organ transplants. Depending on the time at which it occurs after hct, gvhd can be either acute or chronic 4 7.
Pathophysiology of graftversushost disease request pdf. Differential diagnosis the most important distinguishing feature between gvhd and the diagnoses below is the clinical history of bone marrow or solid organ transplant. Acute graft versus host disease orphanet journal of rare. Pdf pathophysiology of graftversushost disease pavan. Graftversushost disease gvhd is a complication that can occur after certain stem cell or bone marrow transplants in which the transplanted cells attack the recipients body. Despite adequate posttransplantation immunosuppressive therapy, acute graft. Acute graftversushost disease agvhd is an immunologically mediated inflammatory. Pathogenesis and management of graft versus host disease.
Despite considerable advances in our understanding of the pathophysiology of graftversushost disease gvhd, its prediction remains unresolved and depends mainly on clinical data. Gvhd is commonly associated with stem cell transplants such as those that occur with bone marrow transplants. Frontiers pathophysiology of gvhd and other hsctrelated. Risk calculators and risk factors for graftversushost disease pathophysiology. Ferrara md professor of medicine and pediatrics director and others published the pathophysiology of graft. Chronic gvhd occurs in 30 to 70% of patients who have undergone allogeneic hematopoietic stemcell transplantation allotransplantation of. In the first phase, highdose chemoradiotherapy causes damage to host tissues, including a selflimited burst of inflammatory cytokines such as tumor necrosis factor tnf alpha and interleukin 1. Remestemcell, the first cellular therapy product for the. Daly alberta blood and marrow transplant program, tom baker cancer center, clinical associate professor, university of calgary, calgary, alberta, canada. Activated donor t cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. Pdf pathophysiology of acute graftversushost disease. However, the major toxicity of allogeneic hct, graftversushost disease gvhd, remains a lethal complication that limits its wider application. The pathophysiology of chronic graftversushost disease. Fifty years ago billingham formulated three requirements for the development of gvhd.
Pathophysiology, prevention, and treatment of acute graft. Graftversushost disease pathophysiology in the news. Acute graft versushost disease gvhd is a significant barrier to the. The pathophysiology of acute gvhd is complex and can be conceptualized to be a threestep process based on. Acute graftacute graftversushost diseasehost disease demographics and population at riskdemographics and population at risk diagnosis and staging clinical presentation response. In the disease, the host body comes under attack from the donated. Clinical characteristics and risk factors for acute graftversushost. The pathophysiology of acute graftversushost disease gvhd is a complex process that can be conceptualized in three phases.
Chronic graftversushost disease gvhd is currently the leading cause of longterm morbidity and mortality following allogeneic hematopoietic stem cell transplantation hsct. This attack is mediated by t cells, a type of white blood cell normally occurring in. Graftversushost disease gvhd, condition that occurs following a bone marrow transplant, in which cells in the donor marrow the graft attack tissues of the recipient the host. Graftversushost disease gvhd is a syndrome, characterized by inflammation in different organs, with the specificity of epithelial cell apoptosis and crypt drop out. Pathophysiology and management of graftversushost disease. In step 1, the conditioning regimen leads to the damage and activation of host tissues and induces the secretion of. Graft versus host disease etiology bmj best practice.
In 1962, barnes and loutit first described gvhd in mice. In acute graftversushost disease, the most common nonhematologic adverse reactions incidence 50% were infections and edema dose modifications may be required when administering jakafi with strong cyp3a4 inhibitors or fluconazole or in patients with renal or hepatic impairment. The occurrence of an immunologically mediated and injurious set of reactions by cells genetically disparate to their host, otherwise known as graft versus host disease gvhd, is a phenomenon that has been described as the age of bone marrow and solid organ transplantation has emerged. Graftversushost disease gvhd is a serious complication that may occur after allogeneic stem cell transplantation. In the first phase, highdose chemoradiotherapy causes damage to host tissues, including a selflimited burst of inflammatory cytokines such as tumor necrosis factor tnf. Chronic graftversushost disease cgvhd after allogeneic hematopoietic stem cell transplantation is still associated with significant morbidity and mortality. In acute gvhd, there is usually a sparse interface or lichenoid lymphocytic infiltrate which infiltrates the epidermis figures 1a, 2a and. M arrs, ms, aprnbc, aocnpa ssociate editor marlana r. Graftversushost disease gvhd what is graftversushost disease gvhd. Pathophysiology of graftversushost disease sciencedirect.
Clinically divided into classic acute graft versus host disease occurring within 100 days of transplant, persistent recurrent late onset acute graft versus host disease occurring 100 days posttransplant and chronic graft versus host disease defined by presence of diagnostic clinical signs and symptoms. Graftversushost disease gvhd is the major cause of morbidity and mortality following allogeneic hsct. Gvhd can be considered an exaggerated, undesirable manifestation of a normal inflammatory mechanism, in which donor lymphocytes encounter foreign antigens in a milieu that fosters. Graftversushost disease gvhd is still a major cause of transplantrelated morbidity and mortality following allogeneic hct allohct.
448 76 1087 361 76 880 721 210 1563 1039 938 110 1331 734 162 306 1571 1633 1640 1126 1602 208 1088 1163 413 583 987 847 1233 753 1008 560 1333 505 806 473 48 1320 193 226 859 621 805