Meet our doctors: Jonathan Cotliar on graft-versus-host disease

February 20, 2015 | by Kim Proescholdt

Each year, thousands of patients with hematologic malignancies undergo allogeneic stem cell transplantation (that is, they receive a donor's stem cells), offering them a chance at cure. Graft-versus-host disease is a potentially deadly complication of this therapy and occurs in approximately 25 to 60 percent of patients. Clinicians and researchers are continually working to reduce the rate of the disease's occurrence and improve outcomes for patients who develop it.

 

Graft-versus-host disease Jonathan Cotliar says earlier intervention is the key to effective treatment for graft-versus-host disease.

 

Here Jonathan Cotliar, M.D., associate clinical professor in dermatology at City of Hope, sorts out the facts about graft-versus-host disease (GVHD). He also describes how the institution's world-class multidisciplinary team of experts excels in treating this complicated disease and how doctors work continuously to better understand and more effectively treat it.

What is GVHD and who is most at risk?

GVHD is, unfortunately, a common complication following allogeneic bone marrow transplant. In GVHD, a component of the donated bone marrow or peripheral blood stem cells views the recipient’s body as foreign and mounts an immune response directed at the transplant recipient, similar to the immune response that might be triggered by a bacterial or viral infection. GVHD can vary in severity, and different parts of the body can be affected either in isolation or in combination with other organ systems.{C}

There are several factors that are thought to increase the development of GVHD. One important factor is donor/recipient human leukocyte antigen (HLA) mismatch, in which there are genetic differences between the recipient and their donor. The differences can cause donor cells to recognize recipient cells as foreign, and lead to an immune response against the recipient’s tissues and organs. Recipients who have received peripheral blood stem cells/bone marrow from an HLA mismatched related donor (or from an HLA matched unrelated donor) have an increased risk of developing GVHD. The advanced age of the recipient can also increase the risk of developing GVHD.

What are the different types of GVHD? What are signs and symptoms that might occur?

GVHD takes one of two forms: acute or chronic. Acute GVHD usually typically occurs early after transplantation (after new bone marrow begins to make blood cells), whereas chronic GVHD usually manifests months to years after transplantation. Although the risk factors for the two are relatively similar, the underlying mechanisms are believed to differ.

The symptoms of acute and chronic GVHD also differ. Patients with acute GVHD tend to have symptoms that include skin rashes that may be itchy and/or painful, diarrhea, liver problems, loss of appetite, and/or nausea and vomiting.

The manifestations of chronic GVHD are notably varied. Red or purple patches on the skin can appear. The gut, liver or mouth can also be affected, as well as other parts of your body, including the eyes, lungs, genitals and joints. Symptoms vary from mild to more severe, where the skin can become thickened, ulcerated and even lead to disfigurement, sometimes hampering the ability to move. For some people the symptoms can continue for years, thus obviously affecting overall quality of life.

GVHD can be difficult to diagnose because certain features may be clinically indistinguishable from infections or adverse reactions to medications.

Knowing the signs and symptoms of GVHD is important so treatment can occur as quickly as possible to prevent more serious complications.

What is standard treatment for GVHD? Are any new therapies available?

Since GVHD can affect multiple organ systems, its management is overseen by a multidisciplinary team of experts that includes dermatologists, oncologists and other cancer specialists. The treatment goals for GVHD are based on prevention, though this is not always possible, but mainly to catch it early and stop the process, preventing the disease from worsening, minimizing GVHD’s effects on quality of life and to prevent long-term toxic effects from the GVHD therapy.

The standard form of treatment for acute GVHD is a prophylaxis regimen that includes providing one or two immunosuppressive medications administered at the time of transplant to preempt the development of acute GVHD. If a patient does indeed develop acute GVHD, even despite this prophylactic treatment, high-dose systemic steroids are typically first line therapy. For those who don’t respond to systemic steroids or aren’t able to wean off them in a timely fashion, there are other forms of treatment, mainly immunosuppressive medications. Unfortunately, no single medication has been proven more effective over the other in this setting.

For chronic GVHD, systemic steroids are the initial treatment. However, there are a variety of treatment options available including, but not limited to, calcineurin inhibitors, extracorporeal photopheresis and a whole host of biologic agents we use here at City of Hope. There are also new drugs and strategies available in clinical trials here at City of Hope that can supplement standard treatment. These drugs, when combined with early detection and advances in our understanding of GVHD, have resulted in significant reductions in serious or potentially harmful outcomes from the disease. Many cases of GVHD are treated successfully.

Why did you choose this area of expertise? What inspires you to do the work you do?

To be at the forefront of clinically groundbreaking research is very exciting. GVHD is a fascinating disease from an immunologic perspective. And from a dermatologic point of view, it has such a wide spectrum of clinical findings that it seems no two patients present to us in the same exact way. It’s not only an intellectual challenge to find the best course of treatment for each patient, but it also becomes a personal mission to prevent GVHD from afflicting patients. It’s extremely rewarding when you know what you do really helps people and makes a difference in their lives. To be able to put a smile back on a patient’s face is a real honor. I feel fortunate every single day to do what I do.

What advice do you have for patients newly diagnosed with GVHD?

I would tell patients that when dealing with GVHD, it is extremely important to always seek out the multidisciplinary care that a team of experts, like those here at City of Hope, can offer. If there is concern you or someone you know and/or care for may potentially have GVHD, it’s important to see and speak to an expert immediately. Don’t wait. The earlier the intervention, the better the outcome.

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Learn more about becoming a patient or getting a second opinion at City of Hope by visiting our website or by calling 800-826-HOPE (4673). You may also request a new patient appointment online. City of Hope staff will explain what's required for a consult at City of Hope and help you determine, before you come in, whether or not your insurance will pay for the appointment.

 

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