Making Sickle Cell Disease a Manageable Illness

By CAROLYN SAYRE

On most days Giovanna Poli acts like a typical 12-year-old. She enjoys riding bikes with her brother, likes learning about the planets in science class and wants to be a pediatrician when she grows up.

But Giovanna, a brown-haired girl from West Palm Beach, Fla., also suffers from debilitating pain, recurring infections and organ damage. She was born with sickle cell disease, a genetic disorder with unpredictable complications that causes the red blood cells to assume an abnormal sickle shape, making it difficult for blood to flow through vessels and deliver oxygen throughout the body.

“I usually feel good,” she says. “But some days it hurts so much in my legs and arms. I can’t really walk, and I don’t like people touching me. If it’s really bad, I have to go to the hospital.”

Every year, nearly 1,000 babies in the United States are born with sickle cell disease, which is thought to affect about 100,000 Americans. Forty years ago, the outlook for babies born with the disease was pretty bleak; the average child lived to be only 14. However, over the last four decades, new treatments, early intervention techniques and newborn screening programs have helped turn this disease, which was once a death sentence, into a manageable chronic illness.

“Our entire approach to treating sickle cell disease has changed,” said Dr. Clinton H. Joiner, director of the division of hematology at Cincinnati Children’s Hospital Medical Center. He notes that today, most patients live to see their 40th birthday.

“Over the last 20 years, we have shifted from treating the complications that arose to preventing the complications altogether,” he said. “It has had a dramatic impact on morbidity and mortality. Today, children are living long enough to become adults.”

Babies with sickle cell disease typically do not exhibit symptoms until after 6 months of age. In the 1970s and ’80s, parents would bring what they thought was an otherwise healthy 6-month-old with a high fever to the emergency room, and the child would often die a few hours later from an overwhelming infection. It was a story all too common; according to Dr. Joiner, some 10 percent of babies with sickle cell disease died within the first four years of life, many before the condition had even been diagnosed.

During the late ’80s, physicians began to realize that the simple act of starting a baby on penicillin could change all that. A major study published in The New England Journal of Medicine in 1986 found that babies with sickle cell anemia — the most common and usually the most serious form of sickle cell disease — who were started on the antibiotic at 4 months of age were less likely to die from pneumococcus, a bacterial infection that commonly strikes children with the disease, than those who did not take the drug. “This has been the single most important disease-modifying therapy,” said Dr. Lanetta B. Jordan, chief medical officer for the Sickle Cell Disease Association of America. “It’s simple, cheap and readily available.”

But having the right drug wasn’t enough. To save lives, penicillin had to be started at an early age, because by the time most babies developed symptoms and a diagnosis was reached, it was usually too late. “It made people realize that if we could diagnose immediately after birth, we could do something to prevent it,” Dr. Joiner said.

As a result, states began to pass legislation requiring that all newborns be screened for sickle cell disease before they leave the hospital. “The goal,” said Dr. George R. Buchanan, director of the Southwest Comprehensive Sickle Cell Center at UT Southwestern Medical Center at Dallas, “was to identify these babies immediately and get them into care.” Since 2006, newborn screening tests for sickle cell disease have been performed in all 50 states.

In addition to infection, stroke was also a leading cause of death in children with sickle cell disease. In fact, before the new millennium, some 10 percent of patients suffered a stroke in the first decade of life. In the late 1990s, however, researchers found a way to identify children who were at risk for stroke using a specialized ultrasound known as transcranial Doppler testing. Today, all children who have sickle cell disease are screened routinely starting at age 2, and those who are found to be at risk are treated with monthly blood transfusions, which can help reduce the risk of stroke by at least 80 percent.

Such screening techniques and early intervention therapies have sharply lowered the mortality rate in children with sickle cell disease. Today, about 90 percent of children make it to adulthood. But according to Dr. Kwaku Ohene-Frempong, an attending hematologist at the Children’s Hospital of Philadelphia, when it comes to quality of life, “we have not made enough progress.”

New therapies, he says, hold promise not only to ease symptoms but also to cure the disease. A drug known as hydroxyurea, which was originally designed to treat cancer, has been found to cut the number of complications from sickle cell disease in half in adults. Recent studies show it has similar benefits in children as well.

“The drug makes the red blood cells look bigger, healthier and behave much better,” Dr. Joiner said. “Some patients go from being completely disabled by their disease to being able to go to school and work after just a few months on this medication.” Physicians like Dr. Joiner are beginning to consider using the drug routinely in young children.

There is also the promise of a cure. Over the last 20 years, at least 400 patients have been cured of sickle cell disease through hematopoietic stem cell transplant, a procedure that replaces the unhealthy sickle-shaped cells with healthy cells from a donor.

The problem, Dr. Jordan points out, “is not that there are not cures, but that the cures that exist cannot be used in the masses.” The procedure is risky at best, the costs are exorbitant, and only 10 to 15 percent of patients are even eligible because they have a full-match donor.

Still, it has patients excited. Giovanna Poli, for one, recently learned her brother is a match, and the family is considering a transplant. Other researchers are working on gene therapy as another approach to cure sickle cell disease, but progress has been slow.

“The future is hopeful, but I don’t see gene therapy or stem cell transplant curing large numbers of patients,” Dr. Buchanan said. “I think it will come down to developing inexpensive, user-friendly, nontoxic medications that keep the cells from causing the damage that they do.”

For now, says Giovanna’s mother, Vivian Poli, the hardest part is the uncertainty. “One minute Giovanna is playing, and the next minute she is in agonizing pain, and there is not much I can do to help her. It is the worst feeling in the world for a parent.”