By Emma Yasinski
BU News Service

Four-year-old Alexander was sitting on a tricycle with one foot on each side resting against the sidewalk like Fred Flintstone when I met him. He hadn’t figured out how to put his feet on the pedals yet, but was using the bike to roll around anyway. And he wasn’t willing to share the toy with his older half-brother. Scrunching his chin against his Mickey Mouse T-shirt, he scowled as he “biked” away as fast as he could. In most ways, Alexander was just like the other boys he was playing with that day, but there was one big difference: a small plastic tube taped to his cheek leading into one nostril from a bag of liquid nutrients in his backpack.

Without this tube, Alexander would starve. It delivers Total Parenteral Nutrition (TPN,) a type of liquid nutrition which he needs to grow and survive. He doesn’t eat chicken nuggets or broccoli like most kids because he doesn’t have the intestines to digest them. Days after he was born, a severe infection attacked the tissue of his digestive system. He eventually beat the disease, but not until a surgeon removed his entire colon and 80% of his small intestine. Alexander can live with this feeding regimen for a while, but eventually it will lead to repetitive infections that send him to the hospital for days or weeks at a time. Only six veins in his body are large enough to receive the TPN. Over time, these veins can get damaged or infected and he won’t be able to receive the liquid any longer. His best chance at an almost-normal life is an intestinal transplant, and he is currently on the waiting list.

Only recently have intestinal transplants become a viable option for patients like Alexander. While other organs, such as kidneys and livers, have been successfully transplanted since the 1960s, the intestines present special difficulties. With any transplant, the patient’s body might reject the new organ, but intestinal transplants pose heightened risks. The immunosuppressant techniques that doctors use for other organ transplants have not been equally effective for intestines. The intestines contain a high concentration of immune cells and bacteria, which makes it difficult for a patient’s body to accept a replacement. Even after the transplant , Alexander will need to live near the hospital for up to a year so that doctors can monitor his immune response several times a week make sure his body is accepting the organ while protecting him against opportunistic infections. Moreover, TPN that nourishes him puts stress on his liver. The longer he waits for his transplant, the more likely it is that his liver will become damaged beyond repair. If that happens, he will need a new liver along with his new intestines.

The intestines house up to 70% of the body’s immune cells, which makes them particularly vulnerable to rejection. These cells protect the large surface area of the intestines from infections that can come from food or the outside world. Unfortunately, this same protective power can turn against the tissue of the new intestine. Since patches of immune cells are found throughout the organ, the attacks take place over its entire length. The immunosuppressant drugs that work for other types of transplants often don’t prevent rejection in intestinal transplant patients. For that reason, long after other transplants procedures had gained success, intestinal transplants continued only as rare, experimental procedures.
Doctors rarely experimented with intestinal transplants until 1994, when the FDA approved a new, powerful immunosuppressant drug called Prograf. Like other immunosuppressants, Prograf dampens the entire immune system, but is much more potent. Prograf’s approval inspired doctors to begin experimenting with the procedure again. Yet stronger immunosuppression comes with a greater risk of infections. Doctors have had to pay increased attention to the recovery of these transplant patients, and have spent years trying different strategies with the drug.

As surgeons continued to experiment with Prograf, the rates of rejection decreased. If he were receiving the transplant in the year 2000, there would have been about a 75% chance that Alexander’s body would reject the intestines. Now, that risk is only about 25%.

Since then, the surgery’s protocol has been standardized, and survival rates are approaching those of other transplants. The national average survival rate for intestinal transplants after three years is currently 70%. (For liver transplants, it is 91%) Rakesh Sindhi, MD, Pediatric Transplant Surgeon at Children’s Hospital of Pittsburgh (where Alexander will have his transplant) attributed the increase in survival to a new strategy for using immunosuppressant drugs; they use very heavy-handed immunosuppression to start, then wean the patient off very quickly. The intensity of the drugs early on wipes out most of the immune cells that can attack the intestines. When the body produces new cells, they are less likely to attack the donated organs and the patient can continue on a much lower dose, minimizing the risk of infections.

While promising, the improved immunosuppression hasn’t solved every issue that Alexander may face. Along with vulnerable lymphoid tissue, the intestines are home to billions of good bacteria that help them to function and digest food. “The immune system evolved simply to combat a foreign agent” says Jeff Browning, PhD Professor of Microbiology and Medicine at Boston University Medical School, “so that’s pretty simple until you get to the gut.” The bacteria that live in the intestines vary from person to person and researchers are just beginning to research how these bacteria interact with an individual’s immune system. Emerging studies have shown that after a transplant, the types of bacteria in the intestines change. It isn’t clear yet why this change occurs, or what role it plays in the transplant process.

Sometime soon, Alexander’s mother will receive a call. The voice on the other end will tell her what she has been waiting to hear for almost two years. When that moment comes, she will one hour to get him to a local hospital. From there, they’ll board a helicopter and fly to a specialized children’s hospital in Pittsburgh in time for the transplant. His father will have to drive and meet them there; there’s only room for one parent in the chopper.

Right now, Alexander and his family are hanging on as best they can while they wait for organs to become available. Once every month or two, he and his family have to head to the hospital while he battles an infection. When he isn’t running around with his brothers, he is practicing eating. Since he’s never had to do it, Alexander needs to learn how to chew and swallow. He is starting with the soft foods, like macaroni and cheese, and working his way up to the chicken nuggets and broccoli. He’ll be ready when it’s finally his turn to eat birthday cake.