Graft-versus-host disease primary prevention
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Graft-versus-host disease |
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Differentiating Graft-versus-host disease from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Primary Prevention
- DNA-based tissue typing allows for more precise HLA matching between donors and transplant patients, which has been proven to reduce the incidence and severity of GVHD and to increase long-term survival.[1].
- The T-cells of umbilical cord blood (UCB) have an inherent immunological immaturity[2], and the use of UCB stem cells in unrelated donor transplants has a reduced incidence and severity of GVHD[3].
- Methotrexate, cyclosporin A and tacrolimus are common drugs used for GVHD prophylaxis.
- Graft-versus-host-disease can largely be avoided by performing a T-cell depleted bone marrow transplant. Umbilical cord blood, for example, contains few T cells and thus confers a decreased risk for GvHD. However these types of transplants come at a cost of diminished graft-versus-tumor effect, greater risk of engraftment failure or cancer relapse[4], and general immunodeficiency, resulting in a patient more susceptible to viral, bacterial, and fungal infection. In a multi-center study, disease-free survival at 3 years was not different between T cell depleted and T cell replete transplants[5].
- Suppression of cytokine-mediated effects can prevent GvHD. It has been postulated that tumor necrosis factor (TNF), derived from T cells, is a major cytokine involved in the pathogenesis of GvHD. Thus, elimination of soluble TNF can be considered as a theoretic prevention strategy.[6] It has been shown that elimination of soluble TNF from donor T lymphocytes caused a delay in GvHD morbidity and mortality.[6] In theory, the use of neutralizing antibodies to TNF could be an important primary preventative strategy.
References
- ↑ Morishima Y, Sasazuki T, Inoko H; et al. (2002). "The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors". Blood. 99 (11): 4200–6. PMID 12010826.
- ↑ Grewal SS, Barker JN, Davies SM, Wagner JE (2003). "Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood?". Blood. 101 (11): 4233–44. doi:10.1182/blood-2002-08-2510. PMID 12522002.
- ↑ Laughlin MJ, Barker J, Bambach B; et al. (2001). "Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors". N. Engl. J. Med. 344 (24): 1815–22. PMID 11407342.
- ↑ Hale G, Waldmann H (1994). "Control of graft-versus-host disease and graft rejection by T cell depletion of donor and recipient with Campath-1 antibodies. Results of matched sibling transplants for malignant diseases". Bone Marrow Transplant. 13 (5): 597–611. PMID 8054913.
- ↑ Lancet 2005 Aug 27-Sep 2;366(9487):733-41
- ↑ 6.0 6.1 Borsotti C, Franklin AR, Lu SX, Kim TD, Smith OM, Suh D; et al. (2007). "Absence of donor T-cell-derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity". Blood. 110 (2): 783–6. doi:10.1182/blood-2006-10-054510. PMC 1924485. PMID 17395784.