Sickle cell anemia remains incurable; treatment improves

Although sickle cell anemia is a life-long illness, these days patients can expect more consistent care and more effective treatments of pain. “For doctors, sickle cell anemia is a very humbling disease. The abnormal gene was defined over 40 years ago, research activities are extensive, and yet we cannot cure most patients,” says Dr. Janis Abkowitz, professor of medicine in the division of hematology at the UW School of Medicine.

“It’s important to individualize treatments so patients can live life to the fullest with the least complications and pain. The approach to managing pain is similar to cancer, but sickle cell pain can be more intense and is episodic rather than chronic,” she adds.

Sickle cell anemia results from abnormal hemoglobin molecules that precipitate inside red blood cells and distort their shape into that of a sickle. This causes the red cells to clog capillaries and sometimes arteries and veins, preventing downstream blood flow and leading to an infarction — an area of dead tissue resulting from the absence of blood delivery — which is extremely painful. Repeated crises over time damage the kidneys, lungs, liver and central nervous system, and can result in death. Because sickled red cells don’t survive as long as normal red cells, patients have anemia.

Sickle cell anemia affects approximately one in every 500 African-American children within the United States. It also affects, to a lesser degree, some people of Hispanic, Arabic, Indian and Mediterranean origin. The gene is present in 9 percent of African Americans, and there is a 25 percent chance that a child will be born with the disease if both parents are carriers.

A couple may have prenatal testing to detect the abnormal gene, and sickle cell anemia can be diagnosed in utero. However, counseling patients on this is difficult. “Other genetic factors clearly modify the progression of sickle cell disease. Different people have different clinical courses, and some individuals have relatively few symptoms throughout their lifetime,” explains Abkowitz.

Most patients die in their 40s, from a crisis involving the lung termed acute chest syndrome, from progressive renal or cardiac failure, or from infection. They are also prone to chronic orthopedic problems, especially in the hips.

Bone marrow or stem cell transplantation can cure sickle cell anemia but the dilemma for doctors is predicting who will need it the most. “Children are the best candidates for transplantation because they have not developed organ failure, and there is less complication from graft versus host disease,” says Abkowitz.

Patients who have had strokes because of sickling in cerebral vessels risk having complications. Although transplants cause the disease to remit, patients may die from seizures or strokes because of previous damage to blood vessels. Cranial Doppler studies are a new technique that may identify children at risk for stroke before there is permanent blood vessel damage.

The other drawback in transplantation is that the drug and radiation regimens required to allow stem cells to engraft can result in infertility or predispose patients to cancer. Also, many sickle cell patients will not have stem cell matches within their family and it is difficult to find matches among unrelated individuals.

The first effective drug for sickle cell anemia was found in 1995, when researchers discovered that the anti-cancer drug, hydroxyurea, increases the amount of fetal hemoglobin within red cells, preventing the cells from sickling. Also, the white blood cell count decreases, leading to less inflammation and pain during residual crises.

Researchers in gene therapy are now studying other ways to alter the hemoglobin production of abnormal cells. Clinical trials could begin within the next three years.

“Sickle cell anemia is a good candidate for gene therapy,” says Abkowitz. “If we had a reliable way to change or transfer genes, there would be a donor for everyone because patients could use their own stem cells.” ¶

Ellen Liang