gvh-picGRAFT vs host disease has been a common chronic disease in older days when tissue grafting derived from other people had been a common practise until the advent of artificial implants. Present day stem cell therapy involves transplantations which has again given triggered the frequency of the disease again. A new therapy has come up to solve the problem, but will it be effective enough?

Graft vs host disease (GVHD) mainly occurs due to the mismatch of the genetic makeup between the host and the donor tissue. There is something called Major Histocompatibility Complex (MHC) which is unique for an individual. Even one’s parents doesn’t have the same MHC. On might find an almost similar match from one’s siblings but it may be approximately a 80% matching at maximum, except in cases of identical twins where one can get a 100% match. It has been seen that GHVD mostly affects the softer tissues only for example skin, liver, stomach, intestine, etc.

Now in case of stem cell transplantation, often the stem cells obtained from an unmatched umblical cord blood or bone marrow, there occurs a MHC mismatch. the host treats the donor stem cells as antigens or foreign bodies, which releases antibody against them. This results in development of inflammations and ultimately rejection of the foreign bodies. In chronic cases it may lead to morbidity.

A new drug known as beclomethasone dipropionate (BDP) has been reported to combat the effect of the GVHD in stomach when stem cells were being injected. Although the drug is still in its clinical trial, it promises a bright future since it has been successful to reduce death due to GVHD down by 45%.

Now let us delve deep into the topic and learn what actually is GVHD and know what the new drug has in store for us.

What is Graft Vs Host Disease?

Graft versus host disease (GVHD) occurs when immunologically competent cells are introduced into an immunoincompetent host. GVHD refers to both the immunologic insult and the consequences to the organism. The leading cause of GVHD is hematopoietic cell transplantation (HCT), both allogeneic (between 2 individuals) and autologous (from the same individual). Solid organ transplants, blood transfusions, and maternal-fetal transfusions also reportedly cause GVHD.

Acute GVHD occurs within the first 100 days of transplantation and consists of the triad of dermatitis, enteritis, and hepatitis. Chronic GVHD develops after day 100 and consists of an autoimmune syndrome directed toward multiple organs. Because the skin often is the earliest organ affected in GVHD, dermatologists are crucial members of the patient’s treatment team.

Acute GVHD usually starts as scattered erythematous macules and papules that involve a greater percentage of total body surface area as the severity of GVHD increases. Erythroderma and bullae may occur in the most severe form of acute GVHD. Chronic GVHD may occur either as a late phase of acute GVHD or as a distinct entity. The skin is the primary organ involved in chronic GVHD, which can manifest as a lichen planus–like eruption or as scleroderma. Despite attempts to manipulate the immune response before, during, and after transplantation, GVHD remains a primary cause of morbidity and mortality after HCT.

The diagnosis of GVHD is complicated by the fact that other eruptions, such as engraftment syndrome, autologous GVHD, viral exanthems and drug eruption, can also occur after transplantation and can have similar histopathological finding as GVHD, making clinical correlation both necessary and complex.For example, zoster can occur after a stem cell transplant and can be confused with acute GVHD.

How GVHD related to stem cell transplantation?

nri2000-f1Graft-Versus-Host Disease is a potentially fatal immune system reaction that occurs in response to a stem cell transplant or a bone marrow transplant of cells from either a related or non-related (allogeneic) donor.

GVHD occurs when the cells of the donor imperfectly match the immune system characteristics (markers) of the host recipient. When this happens, the T-cells of the donor’s body (white blood cells that are immune cells) attack new cells in the host recipient’s body. The immune system of the host recipient will respond using HLA antigens which function to identify which cells belong to the body and which are foreign to it. The antigend will attack the latter. In GVHD, the donor’s immune cells (T-cells) are unable to recognize the HLA antigens found on the cells of the host recipient’s body, causing them to attack the cells.

What are the types of GVHD?

There are two types of Graft-Versus-Host-Disease: acute GVHD and chronic GVHD.

* acute GVHD: in cases of acute GVHD, symptoms appear within 3 months of a transplant. Symptoms can include a reddish skin rash, as well as nausea and diarrhea. If the liver is affected, the skin can become yellow in appearance. Acute GVHD can become:
* chronic GVHD: in cases of chronic GVHD, symptoms appear 3 months after the transplant surgery. Symptoms of chronic GVHD are rated on a scale from 1 (mild) to 4 (severe). Symptoms are similar to those experienced in individuals with acute GVHD and can also include abnormalities of the salivary glands in the mouth (i.e. dry mouth) and the mucous glands of the eyes (dry, irritated eyes). Chronic GVHD can last from several months to many years.

Symptoms of GVHD?

Here is an overview of symptoms:

Acute Symptoms

  • skin rash that is reddish in appearance
  • diarrhea
  • nausea
  • abnormal liver function
  • yellowing of the skin
  • increased susceptibility to infection

Chronic GVHD Symptoms

  • skin rash or change in skin color or texture
  • dry, irritated eyes
  • sensitive or dry mouth

Some less common symptoms associated with chronic GVHD

  • thinning hair
  • brittle nails
  • dry, irritated vaginal region
  • loss of appetite
  • sudden weight loss

Symptoms of GVHD can range from mild to severe.

What the New Therapy has to say in reply to GVHD?

New Therapy that has been clinically tested in 2007, in Fred Hutchinson Cancer Research Center, in gastrointestinal GVHD reactions.

902BDP is an anti-inflammatory drug long used to treat a variety of diseases such as asthma and ulcerative colitis.

About 60 percent of patients who receive an allogeneic stem-cell transplant to treat blood cancers such as acute and chronic myelogenous leukemia, acute lymphocytic leukemia and non-Hodgkin’s lymphoma develop gastrointestinal GVHD as a major side effect of being infused with donor stem cells. Those who show gastrointestinal symptoms of the disease usually receive a two to four-week course of high-dose systemic prednisone therapy that is then tapered slowly. However, that drug is a two-edged sword, Hockenbery said. On the one hand it is designed to suppress the donor cells so GVHD can be controlled. But suppressing the immune system also makes patients susceptible to potentially fatal infections.

In the clinical trial, 129 patients were randomized into two groups. One group received a short course of standard prednisone therapy and oral BDP for 50 days. The other group received a placebo in place of the oral BPD for the same period. At day 10, the prednisone dose was quickly tapered in patients whose symptoms had responded. Fewer patients randomized to BDP had a subsequent flare-up of GVHD. After completion of the 50-day treatment period, patients were followed for an additional 30 days to see if the treatment effect would last. Patients randomized to BDP had a significantly more durable response rate compared to those in the placebo group. At one year after treatment, mortality rates had been reduced 46 percent compared to the placebo group.

“Oral BDP provides much more tailored and targeted control of gastrointestinal GVHD and it allows patients to move away from the side effects of standard prednisone therapy. All of this improves the chances that patients will have a successful outcome,” Hockenbery said. “I think this is a very convincing clinical trial because by targeting topical therapy to the areas most affected, we were able to keep symptoms at bay while minimizing systemic immune suppression.”

Thus we are in a position to wish the success of the drug in the upcoming clinical trials in order to get a respite from this chronic disease. This disease is an unwanted resulting as a side-effect from stem cell therapy. Moreover getting a perfect match as a donor for a particular host is almost a next to an impossible job. So the best way to combat the condition is to get a cure for this disease. Also we are optimistic that starting with gastrointestinal GVHD cure drug, researchers be successful in other cases too.

This in some way or the other help the improvement of stem cell therapy also.