GRAFT VERSUS HOST DISEASE

Posted: October 22, 2013 in Bacterial Contamination

WHAT GRAFT VERSUS HOST DISEASE ( GVHD)??

  • Graft-versus-host disease or GVHD is a term used to describe a battle between the transplanted stem cells and the patient’s body. This is a complication that occurs when the new stem cells (the graft) reject or assume body (the host) as foreign.
  • GVHD is rare in autologous transplants (stem cells come from own blood or bone marrow), it occurs in approximately 50% of patients who have an allogeneic (donor) transplant.
  • GVHD is less likely to occur if the donor and recipient are matched – have identical tissue or “HLA (human leukocyte antigen)” types.

gvhd2 jj

HOW GVHD DEVELOPS?

  • GVDH occur when the transplant affects recipient immune system. T cells from donor’s bone marrow or stem cells will contain some T cells. T cells are a type of white blood cells that function to attack and destroy cells that recognize as foreign and can be harmful to the host.
  • T cells don’t attack body own cells, because they recognize proteins on the cells called HLA (human leukocyte antigens). HLA is inherited protein. Apart from identical twins HLA is unique to each person.
  • Tissue typing is a blood test to check how closely recipient and donor HLA matches. . If recipient and donor have very similar HLA, the chances of GVDH are lower. The more differences there are between recipient HLA and donor, the more likely recipient are to get GVHD.
  • After a transplant recipient bone marrow starts making new blood cells from the donor stem cells. These new blood cells have the donor’s HLA pattern. They recognize the HLA pattern on recipient body cells as different (foreign) and may begin to attack some of them. The GVHD may affect different areas of body. Most commonly it affects the skin, digestive system (including the bowel and stomach) and liver.

TYPES OF GVHD

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SIGNS AND SYMPTOMS

Acute GVHD                    

Involve three main body systems :         graft_vs_host_disease_3_071128 graftversushost

 1.  Skin

  • a rash on the skin surface but it is mostly seen on the hands, feet, abdomen and face.
  • itching, redness on areas of the skin that initially looks sun-burnt.

2. Liver

  • Jaundice (yellow coloring of the skin or eyes)

3. Gastrointestinal Tract

Abdominal pain or cramps, nausea, vomiting, and diarrhea
Chronic GVHD
  •  soreness or dryness of the mouth or eyes
  • lung and liver complications
  • changes in skin pigmentation
  • hair loss
  • weight loss
  • vaginal dryness
  • Cough
  • shortness of breath
  • joint problems

POSSIBLE BENEFITS OF GVHD

  • Although GVDH may have a serious even life threatening problem, it may give a benefit too. In case of transplant for leukaemia, having mild GVHD may be a good thing.
  • As well as attacking recipient body cells, the donor T cells will also attack any remaining leukaemia or cancer cells. Doctors call this the graft versus disease effect, or graft versus leukaemia effect (GVL).
  • The graft means “the donor T cells”. There may also be graft versus disease effect after a transplant for lymphoma or myeloma.

RISK FACTORS OF GVHD

  • Unrelated donor transplants- Risk of developing GVDH is greater if donor and recipient is not related
  • Mismatched donors- If you have a mismatched transplant your donor will be as close an HLA match as possible. But sometimes the best available bone marrow donor is still a slight mismatch. This increases the risk of GVHD.
  • High numbers of T cells in the donated stem cells or bone marrow- Donated stem cells or bone marrow that contain high numbers of T cells are more likely to cause GVHD. This is called a T cell replete stem cell transplant. Whilst this type of transplant may cause more GVHD, it may also lower the chance of relapse.
  • Age- The older recipient and donor  are, the greater recipient risk of developing GVHD.
  • Having a donor of a different sex to you- If donor is a different sex to recipient, the risk of GVHD is slightly increased. This is particularly true if a male has a female donor who has had children or been pregnant in the past.

LABORATORY TESTS

  • Several lab and imaging tests that can be done to diagnose and monitor problems caused by GVHD :
Liver function tests
– –Elevation of the alkaline phosphatase concentration an early sign of liver involvement by GVHD
–Hypoalbuminemia is usually due to GVHD-associated intestinal protein leak and a negative nitrogen balance
Serum electrolytes and chemistries
-–Potassium, magnesium, bicarbonate levels can be altered
–-Massive diarrhoea and diminished oral intake can lead to serious electrolyte abnormalities.
  • A biopsy of the skin, mucus membranes in the mouth, or other parts of the body can help to confirm the diagnosis.

PREVENTION AND TREATMENTS

  • Way to prevent GVDH
1. Tissue typing. 
  • –Tissue typing is a process to match the transplanted donor cells as closely as possible to the host or patient cells.
  • –Of all the proteins in the body, it is crucial to try to match up the proteins called HLA antigens that are found on the surface of all the cells. The mixture of HLA proteins belonging to each of us is inherited equally from our parents. The closer the HLA match between the donor and host tissues, the less likely the outcome of GVHD for the host (patient).
2. Intake of drug before transplant (esp. Stem cell transfusion)
  • –Drug given such as cyclosporine and methotrexate, tacrolimus (Prograf®) and methotrexate, tacrolimus and mycophenolate mofetil (CellCept®) and Prograf and sirolimus (Rapamune®).

 

  • Treatment
1. Intravenously administered glucocorticoids, such as prednisone.
–But this medicines have side effects, including kidney and liver damage so close monitoring is needed.
gvhd
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