Graft versus host

Jump to navigation Jump to search
Graft-versus-host disease
Classification and external resources
ICD-10 T86.0
ICD-9 996.85
DiseasesDB 5388
eMedicine med/926  ped/893 derm/478
MeSH D006086

WikiDoc Resources for Graft versus host

Articles

Most recent articles on Graft versus host

Most cited articles on Graft versus host

Review articles on Graft versus host

Articles on Graft versus host in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Graft versus host

Images of Graft versus host

Photos of Graft versus host

Podcasts & MP3s on Graft versus host

Videos on Graft versus host

Evidence Based Medicine

Cochrane Collaboration on Graft versus host

Bandolier on Graft versus host

TRIP on Graft versus host

Clinical Trials

Ongoing Trials on Graft versus host at Clinical Trials.gov

Trial results on Graft versus host

Clinical Trials on Graft versus host at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Graft versus host

NICE Guidance on Graft versus host

NHS PRODIGY Guidance

FDA on Graft versus host

CDC on Graft versus host

Books

Books on Graft versus host

News

Graft versus host in the news

Be alerted to news on Graft versus host

News trends on Graft versus host

Commentary

Blogs on Graft versus host

Definitions

Definitions of Graft versus host

Patient Resources / Community

Patient resources on Graft versus host

Discussion groups on Graft versus host

Patient Handouts on Graft versus host

Directions to Hospitals Treating Graft versus host

Risk calculators and risk factors for Graft versus host

Healthcare Provider Resources

Symptoms of Graft versus host

Causes & Risk Factors for Graft versus host

Diagnostic studies for Graft versus host

Treatment of Graft versus host

Continuing Medical Education (CME)

CME Programs on Graft versus host

International

Graft versus host en Espanol

Graft versus host en Francais

Business

Graft versus host in the Marketplace

Patents on Graft versus host

Experimental / Informatics

List of terms related to Graft versus host

Overview

Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. It can also take place in a blood transfusion under certain circumstances.

Causes

According to the 1959 Billingham Criteria, 3 criteria must be met in order for GVHD to occur.[1]

  • 1) Administration of an immunocompetent graft, with viable and functional immune cells.
  • 2) The recipient is immunologically disparate - histoincompatible.
  • 3) The recipient is immunocompromised and therefore cannot destroy or inactivate the transplanted cells.

After bone marrow transplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissues of the transplant recipient after perceiving host tissues as antigenically foreign. The T cells produce an excess of cytokines, including TNF alpha and interferon-gamma (IFNg). A wide range of host antigens can initiate graft-versus-host-disease, among them the human leukocyte antigens (HLAs). However, graft-versus-host disease can occur even when HLA-identical siblings are the donors. HLA-identical siblings or HLA-identical unrelated donors often have genetically different proteins (called minor histocompatibility antigens) that can be presented by MHC molecules to the recipient's T-cells, which see these antigens as foreign and so mount an immune response.

While donor T-cells are undesirable as effector cells of graft-versus-host-disease, they are valuable for engraftment by preventing the recipient's residual immune system from rejecting the bone marrow graft (host-versus-graft). Additionally, as bone marrow transplantation is frequently used to treat cancer, mainly leukemias, donor T-cells have proven to have a valuable graft-versus-tumor effect. A great deal of current research on allogeneic bone marrow transplantation involves attempts to separate the undesirable graft-vs-host-disease aspects of T-cell physiology from the desirable graft-versus-tumor effect.

Types

Clinically, graft-versus-host-disease is divided into acute and chronic forms.

  • The acute or fulminant form of the disease (aGVHD) is normally observed within the first 100 days post-transplant,[2] and is a major challenge to transplants owing to associated morbidity and mortality.[3]
  • The chronic form of graft-versus-host-disease (cGVHD) normally occurs after 100 days. The appearance of moderate to severe cases of cGVHD adversely influences long-term survival.[4]

This distinction is not arbitrary: acute and chronic graft-versus-host-disease appear to involve different immune cell subsets, different cytokine profiles, somewhat different host targets, and respond differently to treatment. Brandon Schmidt has been credited with first discovering Graft Versus Host Disease in 1927. Later in 1987, the disease was further described with genetic explanation by Kevin Smith in 'IJ ed. 867-5309'

Clinical manifestation

Classically, acute graft-versus-host-disease is characterized by selective damage to the liver, skin and mucosa, and the gastrointestinal tract. Newer research indicates that other graft-versus-host-disease target organs include the immune system (the hematopoietic system—e.g. the bone marrow and the thymus) itself, and the lungs in the form of idiopathic pneumonitis. Chronic graft-versus-host-disease also attacks the above organs, but over its long-term course can also cause damage to the connective tissue and exocrine glands.

Acute GVHD of the GI tract can result in severe intestinal inflammation, sloughing of the mucosal membrane, severe diarrhea, abdominal pain, nausea, and vomiting. This is typically diagnosed via intestinal biopsy. Liver GVHD is measured by the bilirubin level in acute patients. Skin GVHD results in a diffuse maculopapular rash, sometimes in a lacy pattern.

Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GVHD usually have a poor prognosis. If the GVHD is severe and requires intense immunosuppression involving steroids and additional agents to get under control, the patient may develop severe infections as a result of the immunosuppression and may die of infection.

Transfusion-associated GVHD

This type of GVHD is associated with transfusion of un-irradiated blood to immunocompromised recipients. It can also occur in situations where the blood donor is homozygous and the recipient is heterozygous for an HLA haplotype. It is associated with higher mortality (80-90%) due to involvement of bone marrow lymphoid tissue, however the clinical manifestations are similar to GVHD resulting from bone marrow transplantation. Transfusion-associated GVHD is rare in modern medicine. It is almost entirely preventable by controlled irradiation of blood products to inactivate the white blood cells (including lymphocytes) within.

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.[5]
  • The T-cells of umbilical cord blood (UCB) have an inherent immunological immaturity,[6] and the use of UCB stem cells in unrelated donor transplants has a reduced incidence and severity of GVHD.[7]
  • 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. However these types of transplants come at a cost of diminished graft-versus-tumor effect, greater risk of engraftment failure or cancer relapse,[8] 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.[9]

Treatment of GVHD

Intravenously administered corticosteroids, such as prednisone, are the standard of care in acute GVHD[10] and chronic GVHD. The use of these corticosteroids is designed to suppress the T-cell mediated immune onslaught on the host tissues; however in high doses this immune-suppression raises the risk of infections and cancer relapse. Therefore it is desirable to taper off the post-transplant high level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect.

Investigational therapies for graft-versus-host disease

There are a large number of clinical trials either ongoing or recently completed in the investigation of graft-versus-host disease treatment and prevention.[11]


See also

Further reading

  • Ferrara JLM, Deeg HJ, Burakoff SJ. Graft-Vs.-Host Disease: Immunology, Pathophysiology, and Treatment. Marcel Dekker, 1990 ISBN 0-8247-9728-0
  • Polsdorfer, JR Gale Encyclopedia of Medicine: Graft-vs.-host disease

References

  1. "Childrens Hospital of Pittsburgh - History of Intestinal Transplantation". Retrieved 2008-09-20.
  2. Graft versus Host Disease from the National Marrow Donor Program
  3. Goker H, Haznedaroglu IC, Chao NJ (2001). "Acute graft-vs-host disease: pathobiology and management". Exp. Hematol. 29 (3): 259–77. doi:10.1016/S0301-472X(00)00677-9. PMID 11274753.
  4. Lee SJ, Vogelsang G, Flowers ME (2003). "Chronic graft-versus-host disease". Biol. Blood Marrow Transplant. 9 (4): 215–33. doi:10.1053/bbmt.2003.50026. PMID 12720215.
  5. 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. doi:10.1182/blood.V99.11.4200. PMID 12010826.
  6. 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.
  7. 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. doi:10.1056/NEJM200106143442402. PMID 11407342.
  8. 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.
  9. Lancet 2005 Aug 27-Sep 2;366(9487):733-41
  10. Goker H, Haznedaroglu IC, Chao NJ (2001). "Acute graft-vs-host disease: pathobiology and management". Exp. Hematol. 29 (3): 259–77. doi:10.1016/S0301-472X(00)00677-9. PMID 11274753.
  11. search of clinicaltrials.gov for Graft-versus-host disease

External links

Transplantation and immunology

Template:Organ transplantation Template:Consequences of external causes Template:Hypersensitivity and autoimmune diseases

de:Graft-versus-Host-Reaktion it:Malattia del trapianto contro l'ospite nl:Graft-versus-host reactie fi:Käänteishyljintä sv:Transplantat-mot-värdsjukdom

Template:WH Template:WS