Graft-versus-host disease primary prevention: Difference between revisions
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The following are strategies that have been used, or have been proposed in theory, for primary prevention of GvHD. | The following are strategies that have been used, or have been proposed in theory, for primary prevention of GvHD. | ||
*[[Methotrexate]], [[cyclosporin A]], [[tacrolimus]] and [[ | *[[Methotrexate]], [[cyclosporin A]], [[tacrolimus]] and [[sirolimus]] are common drugs used for GVHD prophylaxis. Methotrexate is typically started after stem cell transplant is performed. Sirolimus acts via inhibition of mTOR, thus inhibiting downstream signal transduction mediators that eventually lead to transcription of proteins involved in cell cycle progression for T cells.<ref name="pmid19539221">{{cite journal| author=Pidala J, Kim J, Anasetti C| title=Sirolimus as primary treatment of acute graft-versus-host disease following allogeneic hematopoietic cell transplantation. | journal=Biol Blood Marrow Transplant | year= 2009 | volume= 15 | issue= 7 | pages= 881-5 | pmid=19539221 | doi=10.1016/j.bbmt.2009.03.020 | pmc=4856158 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19539221 }} </ref> One downside of sirolimus for primary prevention is that there is a risk for thrombotic microangiopathy, which has resulted in some hesitancy by clinicians to use this medication in the preventative setting.<ref name="pmid19539221">{{cite journal| author=Pidala J, Kim J, Anasetti C| title=Sirolimus as primary treatment of acute graft-versus-host disease following allogeneic hematopoietic cell transplantation. | journal=Biol Blood Marrow Transplant | year= 2009 | volume= 15 | issue= 7 | pages= 881-5 | pmid=19539221 | doi=10.1016/j.bbmt.2009.03.020 | pmc=4856158 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19539221 }} </ref> | ||
*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.<ref>{{cite journal |author=Morishima Y, Sasazuki T, Inoko H, ''et al'' |title=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 |journal=Blood |volume=99 |issue=11 |pages=4200–6 |year=2002 |pmid=12010826 |doi= |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=12010826}}</ref>. | *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.<ref>{{cite journal |author=Morishima Y, Sasazuki T, Inoko H, ''et al'' |title=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 |journal=Blood |volume=99 |issue=11 |pages=4200–6 |year=2002 |pmid=12010826 |doi= |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=12010826}}</ref>. | ||
Revision as of 16:22, 12 June 2017
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Graft-versus-host disease |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Primary prevention focuses on interventions that inhibit the onset of a disease or condition before the disease or condition even occurs. Primary prevention of GvHD refers to prevention of GvHD in patients who will receive a stam cell transplant. Primary prevention is highly important because GvHD can have high morbidity and mortality once the disease begins, and treatments like corticosteroids have adverse effects which can futher contribute to morbidity and mortality. Thus, there is an strong effort by clinicians to prevent the onset of GvHD. There are a few primary prevention aspects for GvHD.
Primary Prevention
The following are strategies that have been used, or have been proposed in theory, for primary prevention of GvHD.
- Methotrexate, cyclosporin A, tacrolimus and sirolimus are common drugs used for GVHD prophylaxis. Methotrexate is typically started after stem cell transplant is performed. Sirolimus acts via inhibition of mTOR, thus inhibiting downstream signal transduction mediators that eventually lead to transcription of proteins involved in cell cycle progression for T cells.[1] One downside of sirolimus for primary prevention is that there is a risk for thrombotic microangiopathy, which has resulted in some hesitancy by clinicians to use this medication in the preventative setting.[1]
- 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.[2].
- T cells of umbilical cord blood (UCB) have an inherent immunological immaturity.[3], and the use of UCB stem cells in unrelated donor transplants has a reduced incidence and severity of GVHD[4].
- 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[5], 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[6].
- 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.[7] It has been shown that elimination of soluble TNF from donor T lymphocytes caused a delay in GvHD morbidity and mortality.[7] In theory, the use of neutralizing antibodies to TNF could be an important primary preventative strategy.
References
- ↑ 1.0 1.1 Pidala J, Kim J, Anasetti C (2009). "Sirolimus as primary treatment of acute graft-versus-host disease following allogeneic hematopoietic cell transplantation". Biol Blood Marrow Transplant. 15 (7): 881–5. doi:10.1016/j.bbmt.2009.03.020. PMC 4856158. PMID 19539221.
- ↑ 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
- ↑ 7.0 7.1 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.