Patients with blood cancers like leukemia can often be cured with a stem cell transplant from a donor. But up to 50% of patients who are cured of cancer with this type of transplant suffer when the donor immune system attacks the patient’s own organs. Most cases of this graft-vs.-host disease are successfully treated with steroid medications, but other patients suffer from pain, rashes, and bloody diarrhea, and sometimes die from infections.
Now a physician scientist at the University of Texas MD Anderson Cancer Center is studying how graft-vs.-host disease can be prevented by paying attention to a less-widely-known modulator of the immune system: the gut microbiome.
Dr. Robert Jenq, M.D., was recruited to MD Anderson from Memorial Sloan Kettering Hospital in New York, with the help of a Recruitment of Rising Stars Award from CPRIT.
In his role as a bone marrow transplant oncologist, Dr. Jenq became concerned about patients who suffered from graft-vs.-host disease after successfully beating cancer. He found that the patients who fared worst had been treated with a broad-spectrum antibiotic during the transplant process.
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Patients with blood cancers like leukemia can often be cured with a stem cell transplant from a donor. But up to 50% of patients who are cured of cancer with this type of transplant suffer when the donor immune system attacks the patient’s own organs. Most cases of this graft-vs.-host disease are successfully treated with steroid medications, but other patients suffer from pain, rashes, and bloody diarrhea, and sometimes die from infections.
Now a physician scientist at the University of Texas MD Anderson Cancer Center is studying how graft-vs.-host disease can be prevented by paying attention to a less-widely-known modulator of the immune system: the gut microbiome.
Dr. Robert Jenq, M.D., was recruited to MD Anderson from Memorial Sloan Kettering Hospital in New York, with the help of a Recruitment of Rising Stars Award from CPRIT.
In his role as a bone marrow transplant oncologist, Dr. Jenq became concerned about patients who suffered from graft-vs.-host disease after successfully beating cancer. He found that the patients who fared worst had been treated with a broad-spectrum antibiotic during the transplant process.
Dr. Jenq realized that the antibiotics were killing off not only infectious bacteria, but also beneficial gut bacteria. These bacteria interact with the immune system in ways that are still not fully understood. But, using mouse models of donor-stem–cell transplants, Dr. Jenq discovered that the intestinal bacteria most likely to be affected by the antibiotics were a protective type called Chlostridia. At the same time, bacteria known to digest the mucus layer of the gut, called Akkermansia, were thriving. The thinned-out mucus layer in the mice’s colons made them less able to cope when with other intestinal bacteria.
Based on his findings in mice, Dr. Jenq and his colleagues are planning a clinical trial for about 50 blood cancer patients receiving donor stem cell transplants at MD Anderson. First, doctors will continue their standard practice of avoiding giving antibiotics if possible, particularly antibiotics that would injure the gut microbiome. Second, if patients contract a serious infection—a possible complication for immune-suppressed patients—and need strong antibiotics, doctors would add a different antibiotic to prevent a bloom of potentially harmful, mucus-digesting bacteria. Third, Dr. Jenq plans to study how well a technique known as a fecal transplant—transferring the gut microbiome from a healthy person—would help patients with compromised microbiomes restore a healthy gut flora and prevent graft-vs.-host disease.
A second, multicenter clinical trial Dr. Jenq plans will involve about 50 patients with advanced graft-vs.-host disease. These patients have few if any treatment options. Dr. Jenq will see if fecal transplants enable them to recover from life-threatening complications.
“This type of clinical trial is very important to patient health and survival,” Dr. Jenq says, “but it’s not something that any pharmaceutical company would be interested in funding, because they can’t make any money from it. We’re dependent on the support of CPRIT. It fills a critical need.”
If it turns out that the fecal transplants are successful, then biotech companies may be interested, he says, because they can develop a quality-controlled mixture of bacteria that can be delivered safely and easily to a patient.
Dr. Jenq received his undergraduate degree from Princeton University and M.D. from Oregon Health Sciences University in Portland. He was a resident in internal medicine at Duke University Medical Center in Durham, N.C., prior to going to Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York in 2004. He became an assistant professor at Memorial Sloan-Kettering and Weill Cornell in 2013.
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