Graft-versus-host disease
Graft-versus-host disease | |
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Mouse colon impacted by acute graft-versus-host disease | |
Specialty | Emergency medicine |
Graft-versus-host disease (GvHD) is a
White blood cells of the donor's immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). The white blood cells present within the transplanted tissue then attack the recipient's body's cells, which leads to GvHD. This should not be confused with a transplant rejection, which occurs when the immune system of the transplant recipient rejects the transplanted tissue; GvHD occurs when the donor's immune system's white blood cells reject the recipient. The underlying principle (alloimmunity) is the same, but the details and course may differ.
GvHD can also occur after a blood transfusion, known as Transfusion-associated graft-versus-host disease or TA-GvHD if the blood products used have not been gamma irradiated or treated with an approved leukocyte reduction system. In contrast to organ/tissue transplant associated GvHD, the incidence of TA-GvHD is increased with HLA matching (first-degree or close relatives).[1]
Types
In the clinical setting, graft-versus-host disease is divided into
In the classical sense, acute graft-versus-host disease is characterized by selective damage to the
Mucosal damage to the
Acute
The acute or fulminant form of the disease (aGvHD) is normally observed within the first 10 to 100 days post-transplant,
The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body. Other symptoms can include nausea, vomiting, stomach cramps, diarrhea (watery and sometimes bloody), loss of appetite, jaundice, abdominal pain, and weight loss.[10]
Acute GvHD of the
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[12] as a result of the immunosuppression and may die of infection. However, a 2016 study found that the prognosis for patients with grade IV GvHD has improved in recent years.[15]
Chronic
The chronic form of graft-versus-host disease (cGvHD) normally begins 90 to 600 days post-transplant.[10] The appearance of moderate to severe cases of cGVHD adversely influences long-term survival.[16]
The first symptom of cGvHD is commonly a rash on the palms of the hands or the soles of the feet, and the rash can spread and is usually itchy and dry. In severe cases, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic GVHD can include:[10]
- Decreased appetite
- Diarrhea
- Abdominal (belly) cramps
- Weight loss
- Yellowing of the skin and eyes (jaundice)
- Enlarged liver
- Bloated abdomen (belly)
- Pain in the upper right part of the abdomen (belly)
- Increased levels of liver enzymes in the blood (seen on blood tests)
- Skin that feels tight
- Dry, burning eyes
- Dryness or painful sores in the mouth
- Burning sensations when eating acidic foods
- Bacterial infections
- Blockages in the smaller airways of the lungs
In the
Causes
Three criteria, known as the Billingham criteria, must be met in order for GvHD to occur.[18]
- An immuno-competentgraft is administered, with viable and functional immune cells.
- The recipient is immunologically different from the donor – histo-incompatible.
- The recipient is immunocompromised and therefore cannot destroy or inactivate the transplanted cells. In particular, it involves an inability of the recipient's cell-mediated immunity to destroy or inactivate viable lymphocytes from the donor.[19]
After bone marrow transplantation,
Antigens most responsible for graft loss are HLA-DR (first six months), HLA-B (first two years), and HLA-A (long-term survival).[23]
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
Transfusion-associated GvHD
This type of GvHD is associated with
Thymus transplantation
Thymoma-associated multiorgan autoimmunity (TAMA)
A GvHD-like disease called thymoma-associated multiorgan autoimmunity (TAMA) can occur in patients with thymoma. In these patients rather than a donor being a source of pathogenic T cells, the patient's own malignant thymus produces self-directed T cells. This is because the malignant thymus is incapable of appropriately educating developing thymocytes to eliminate self-reactive T cells. The result is a disease virtually indistinguishable from GvHD.[30]
Mechanism
The pathophysiology of GvHD includes three phases:[31]
- The afferent phase: activation of APC (antigen presenting cells)
- The efferent phase: activation, proliferation, differentiation and migration of effector cells
- The effector phase: target tissue destruction
Activation of APC occurs in the first stage of GvHD. Prior to haematopoietic stem cell transplantation, radiation or chemotherapy results in damage and activation of host tissues, especially intestinal mucosa. This allows the microbial products to enter and stimulate pro-inflammatory cytokines such as
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.[34]
- The T-cells of umbilical cord blood (UCB) have an inherent immunological immaturity,[35] and the use of UCB stem cells in unrelated donor transplants has a reduced incidence and severity of GvHD.[36]
- cyclosporin and tacrolimus are common drugs used for GvHD prophylaxis.[37] Further research is necessary to evaluate whether mesenchymal stromal cells can also be used for the prophylaxis.[38]
- 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,
Treatment
Glucocorticoids
Intravenously administered
Steroid-sparing immunosuppression/immunomodulation
Other substances that have been studied for GvHD treatment include, for example: sirolimus, pentostatin, etanercept, and alemtuzumab.[44]
In August 2017, the
Clinical research
There are a large number of clinical trials either ongoing or recently completed in the investigation of graft-versus-host disease treatment and prevention.[46]
On May 17, 2012, Osiris Therapeutics announced that Canadian health regulators approved
In January 2016, Mesoblast released results of a phase 2 clinical trial on 241 children with acute Graft-versus-host disease, that was not responsive to steroids.[48] The trial was of a mesenchymal stem cell therapy known as remestemcel-L or MSC-100-IV. Survival rate was 82% (vs 39% of controls) for those who showed some improvement after one month, and in the long term 72% (vs 18% of controls) for those that showed little effect after one month.[48]
HIV elimination
Graft-versus-host disease has been implicated in eliminating several cases of HIV, including
See also
References
- PMID 9875072.
- PMID 28373870.
- S2CID 24811357.
- PMID 16338616.
- PMID 26209034.
- PMID 20371463.
- S2CID 39209313.
- PMID 14677115.
- PMID 27982319.
- ^ a b c d e f "Stem Cell or Bone Marrow Transplant Side Effects". www.cancer.org. Retrieved 2020-09-01.
- ^ PMID 11274753.
- ^ a b "Graft-versus-host disease". MedlinePlus. National Library of Medicine. Retrieved 6 May 2019.
- PMID 22296496.
- S2CID 25151282.
- ^ PMID 26748160.
- PMID 12720215.
- PMID 30726819.
- PMID 4875305.
- PMID 7927137.)
{{cite journal}}
: CS1 maint: multiple names: authors list (link - S2CID 1585777.
- S2CID 73449161.
- PMID 21727137.
- PMID 25516409.
- PMID 29222323.
- PMID 18539902.
- S2CID 7462268.
- S2CID 24007739.
- S2CID 219575147.
- PMID 17284531.
- PMID 17433850.
- PMID 28373413.
- S2CID 7043844.
- S2CID 25250676.
- S2CID 6859250.
- S2CID 6486524.
- PMID 11407342.
- PMID 27662016.
- PMID 30697701.
- PMID 8054913.
- S2CID 33732870.
- S2CID 27292769.
- ^ PMID 36923700.
- S2CID 22094672.
- ^ a b Mandanas RA. "Graft Versus Host Disease Treatment & Management: Medical Care". Medscape. Retrieved 30 August 2017.
- ^ Research, Center for Drug Evaluation and (February 9, 2019). "FDA expands ibrutinib indications to chronic GVHD". FDA – via www.fda.gov.
- ^ "Search of: Graft-versus-host disease - List Results - ClinicalTrials.gov". clinicaltrials.gov.
- ^ "World's First Stem-Cell Drug Approval Achieved in Canada". The National Law Review. Drinker Biddle & Reath LLP. 2012-06-12. Retrieved 2012-07-01.
- ^ a b "Increased Survival Using MSB Cells In Children With aGVHD". Retrieved 22 Feb 2016.
- ^ "Immune war with donor cells after transplant may wipe out HIV". ?. NewScientist. 2017-05-03. Retrieved 2018-11-23.
Further reading
- Ferrara JLM, Deeg HJ, ISBN 0-8247-9728-0
- Polsdorfer, JR Gale Encyclopedia of Medicine: Graft-vs.-host disease
External links
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