Stem cell therapy is a two-step process. First, the patients blood cells are destroyed by chemotherapy, radiation therapy or immunosuppression. This conditioning process also eradicates any cancer cells that survived first-line treatment. Second, the patient receives stem cells harvested from a donors bone marrow or peripheral blood (circulating blood). While this can be an effective cure, it can cause graft-versus-host disease (GVHD) in up to 50% of patients. GVHD is more likely to develop in patients who have received a peripheral blood transplant and can kill 15%-20% of patients.

Two types of GVHD can develop, acute and chronic, and patients may develop either one, both or neither type. GVHD is less likely to occur and symptoms are milder if the donor cells closely match those of the patient. Acute GVHD can develop within 100 days of a transplant. The first step of stem cell therapy can cause tissue damage, and bacteria from the gut can escape into the bloodstream. This primes the patients antigen-presenting cells (cells that activate the immune response), which subsequently encourage donor T cells to proliferate and attack the patients tissues. Symptoms include vomiting, diarrhea, skin rashes, nausea, vomiting and liver problems. This can be resolved relatively quickly in one third of patients using immunosuppressive treatments, but some patients can progress to chronic GVHD.

The biological mechanisms responsible for chronic GVHD are not completely understood, but scientists believe that other immune system cells from the donor (B cells and macrophages) are stimulated and damage the patients tissues. Symptoms include dry eyes, mouth sores, muscle weakness, fatigue and joint problems.

Unfortunately, development of effective treatments for GVHD is not keeping up with the increasing number of GVHD patients or with advances in understanding this disease. At present, standard treatments include corticosteroids and drugs that reduce IL-2, an immune system chemical that helps T-cells multiply and diversify. These treatments have various side effects including suppressing the patients immune system, thereby increasing risk of infection.

One challenge stalling drug research is that a small degree of graft-versus-host response must occur for successful stem cell therapy: donor cells will destroy any cancer cells that remain after the first stage of therapy. This challenge is discussed in a recent article in Science Health.Although several treatments have been trialed, success is variable and often targets only acute GVHD or chronic GVHD. Biomarkers have also been detected that may help identify individuals at risk of developing severe GVHD, information that may aid the development of personalized treatment strategies. Drugs that have been approved for other diseases, but not for GVHD, show promise and include ibrutinib for chronic GVHD (approved for specific blood cancers) and ruxolitinib for acute GVHD (approved for bone marrow disorders).

The impact of stem cell therapy must not be underestimated: up to 50% of recipients will develop GVHD. Unfortunately, some individuals will develop chronic GVHD, a condition that is just as difficult to survive as cancer. This highlights the importance of developing continued care strategies for individuals receiving stem cell therapy as a final defence against cancer.

Written byNatasha Tetlow, PhD

Reference: Cohen J. A stem cell transplant helped beat back a young doctors cancer. Now, its assaulting his body. Science Health. 2017. Available at: DOI: 10.1126/science.aan7079

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