Hematology Specialist Association 19 National Congress
Mais dadosGraft‐versus‐host disease (GvHD) is an important complication that can be observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The incidence of Acute GvHD (aGvHD) is around 30%-50% in HLA fully matched allo-HSCT. aGvHD is also common in haploidentical and matched unrelated donor transplantation.
The mechanism underlying tissue damage in aGvHD is massive inflammatory cytokine secretion. Proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] are seen, as well as the increased expression of the receptor repertoire (pattern recognition receptors) on antigen-presenting cells.
The most important risk factor for GvHD is HLA mismatch. Other risk factors include sex disparity between donor and recipient, the intensity of the conditioning regimen, increased age, multiparous female donors, ineffective GvHD prophylaxis, and the source of the graft. A study showed that aGvHD was significantly more common with total body irradiation involving a myeloablative regimen and peripheral stem cell transplantation from a fully matched related donor.
GvHD can be acute or chronic based on the clinical presentation and its occurrence after or before 100 days after allo-HSCT. aGvHD may occur beyond this arbitrary cut-off of 100 days. The widely accepted National Institutes of Health consensus criteria havebeen used to classify GvHD. GvHD is divided into four subclasses: 1) Classic aGvHD: Diagnostic and distinctive features of chronic GvHD (cGvHD) are absent. Clinical features of aGvHD and present within 100 days of allo-HSCT or donor lymphocyte infusion (DLI). 2) Persistent and/or recurrent late-onset aGvHD: Features of classic aGvHD without diagnostic manifestations of cGvHD occurring beyond 100 days after allo-HSCT or DLI. 3) Classic cGvHD: Present at any time after HSCT. Diagnostic and distinctive features of cGvHD are present without aGvHD. 4) Overlap syndrome; Features of both cGvHD and aGvHD can be seen.
The most commonly affected organsa are:Skin,eyes,oral mucosa,liver,GIS tract,genital organs,lungs,joints and fascia.
The most important step for the prevention of GvHD is minimizing risk factors with donor selection and a preparative regimen. GvHD prophylaxis is essential for patients undergoing allo-HSCT. Guidelines for GvHD prophylaxis have been proposed by the European Group for Blood and Marrow Transplantation and European LeukemiaNet . The most common form of GvHD prophylaxis has been the combination of cyclosporine and a short course of methotrexate, which demonstrated improved survival compared to either drug alone. Both cyclosporine and tacrolimus decreased the proliferation of T-lymphocytes . Tacrolimus plus methotrexate is better in decreasing the risk for aGvHD than the combination of cyclosporine and methotrexate, particularly in unrelated HSCT. Both regimens are considered as cornerstones for most GvHD prevention strategies for patients receiving allo HSCT. The effects of the addition of corticosteroids to the combination of cyclosporine and a short course of methotrexate have shown conflicting results.
Calcineurin inhibitors and Ruxolitinib, a JAK 1/2 inhibitor, are also used as prophylactic treatment.
Unfortunately, there is no standard indication or timing for the initiation of therapy for GvHD. Many agents have been tested alone or in combination with corticosteroids. Extracorporeal photopheresis (ECP), mycophenolate mofetil, sirolimus, everolimus, rituximab, and ibrutinib are available options.




