MEDICAl BLOGS:GRAFT VERSUS HOST DISEASE (GVHD)

The high dose chemotherapy given for certain types of cancer, is called myeloablative therapy because it kills all the normal bone marrow stem cells in addition to killing the cancer cells.In the Allogenic setting, the bone marrow/stem cells, from HLA matched donor, which has already been collected from the donors marrow/stem cells(collected from the bone marrow/ donor peripheral blood via a cell separator) is then infused into the patient ( recipient) with a view to rescue the patient.

RESCUE:

These donor transfused stem cells then home on to the recepient marrow sites and gradually over a period starting from around 14 days onwards, help in re formation of all the three cell lines( RBC, WBC & platelets) in the recipient.  The time for theprocess of recovery  given is variable, but within 4 weeks post PSCT and longer for the post BMT cases.

WHAT IS GVHD?

GVHD is the phenomenon observed as a complication following an Allogenic Bone Marrow Transplant (BMT)or Peripheral blood Stem Cell Transplant (PSCT).GVHD happens when a type of WBC,called the T cells, present in the donorbone, attacks the recipients body cells. 

WHY DOES GVHD HAPPEN?

We all inherit our HLA from our parents which is unique for each one of us, except in identical twins ( who have the same HLA). That is why blood tests are done prior to transplant for the donor and recipient to see how far the HLA match one another.Post transplant, the patient (recipient) bone marrow starts making new blood cells from the donor stem cells. These new blood cells have the donor's HLA pattern. They recognise the HLA pattern on the host (recipient) body cells as foreign and therefor attack some of them. 

The GVHD may affect different areas of the recipient's body. Most commonly it affects the Skin, Digestive system (including the bowel and stomach) and the Liver. 

TYPES OF GVHD:

GVHD can be grouped according to when it starts after your transplant. 

• Chronic GVHD
• Late acute GVHD and overlap syndrome
• Acute GVDH

Acute GVHD:

Acute GVHD, starts within 100 days of the transplant and can be mild or severe. It starts after the new bone marrow begins to make blood cells,the process called Engraftment which usually happens in about 2 to 3 weeks after transplant. 

Acute GVHD may present as :A rash on the palms, soles, ears or even face of recipient. The rash may be itchy or painful. Acute GVHD may also affect the mouth, gut (digestive system) and liver and lead to nausea, loss of appetite, diarrhea and yellowing of the skin (jaundice).

Chronic GVHD:

Chronic GVHD normally starts more than 100 days after the transplant. It normally follows Acute GVHD, but can happen even by itself and affectsthe skin, mouth, gut, liver, eyes, lungs, vagina and joints. 

•  Skin: rash, discoloration, tightness or changes in texture
• Hair: thinning
•  Nails: changes in texture, brittleness or ridges
•  Eyes: irritation, dryness, blurred vision, a gritty feeling
• Mouth: dryness, sensitivity to foods or toothpaste
• Vagina: dryness, irritation, tightening
• Penis: irritation
• Digestive System: nausea, vomiting, diarrhea, loss of appetite, unexplained weight loss
•  Lungs: chronic cough, wheezing, shortness of breath
• Joints: difficulty fully extending fingers, wrists, elbows, knees or ankles
•  Fatigue
•  Low grade fever

Chronic GVHD may be mild or severe, and for some people can go on for several months or even years.

Late acute GVHD and overlap syndrome:

The National Institutes of Health classification includes late acute GVHD (starting after day 100) and an overlap syndrome with features of both acute and chronic GVHD. They are both more likely to happen after mini transplants (reduced intensity conditioning)

Risk factors for GVHD:

A number of factors can increase your risk of GVHD. These include the following

• Unrelated donor transplants. 
• Mismatched donor transplant.
• Large number of T cells in donor marrow/stem cells
• Age:Older the donor or recipient more chances of developing GVHD.
• Having a donor of a different sex to you: If your donors sex is different, the risk of GVHD is slightly increased. More true if a male is the recipient and female a donor who has had children or been pregnant in the past.
• Testing positive for cytomegalovirus (CMV): An otherwise common harmless virus observed in 60% of general population. But if recipient is CMV negative and Donor CMV positive the risk for GVHD is greater.

Benefits of GVHD:

GVHD can be unpleasant and reduce quality of life and in some cases it can be life threatening.

But mild GVHD can lower the chance of leukaemia or lymphoma coming back (relapse) by the graft versus cancer effect provided by the Donor T cells which kill the remains cancer cells.

Therefore treatments to prevent/reduce GVHD are used very judiciously so that the benefits of GRAFT VERSUS DISEASE EFFECT is not lost.

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Author- 

   

Dr. Ganjoo 

Head-Yoddhas Medical Expert Panel