Sickle Cell Disease

80,000 Americans have sickle cell disease and Pamela Newton, a Baltimore resident, is one woman who no longer suffers from it. She is the first woman to undergo an experimental bone marrow transplant at Johns Hopkins Hospital that rendered her free of sickle cell disease.

Sickle cell disease predominantly affects blacks and Hispanics. The disease is a genetic mutation in which patients inherit two forms of abnormal hemoglobin. There are only three types of normal hemoglobin. Hemoglobin helps red blood cells carry iron.

Hemoglobin A is the adult form that contains a pair of alpha and beta chains.
Hemoglobin A2 is formed during the third trimester of pregnancy and makes up about 3% of adult hemoglobin.
Hemoglobin F is fetal hemoglobin that decreases after birth and by six months there is a classic hemoglobin "switch" to adult hemoglobin A.

The hemoglobin in sickle cell disease is Hemoglobin SS and in patients the red blood cells no longer have the normal round biconcave shape. Rather, the shape of red blood cells becomes more like a crescent moon shape. In sickle cell patients, the shape of red blood cells makes it easier for the cells to hook into each other and form clumps that get trapped in blood vessels. The entrapment of red blood cells blocks off blood flow to organs. Preventing oxygen rich blood from getting to vital organs leads to excruciating pain and infection. People may live with the disease until their forties.

Dr. Ephraim Fuchs and Dr. Leo Luznik developed the procedure at Johns Hopkins. It offers an alternative to performing bone marrow transplants in children. For over 20 years, 200 children have been cured of sickle cell disease through bone marrow transplants. The newer approach relieves parents from making the early decision for surgery in their children's lives as the procedure has a mortality rate of 5% to 10%.

Pamela Newton, now doing well, underwent this procedure 15 months ago when she was given but just a few months to live. Unlike previous bone marrow transplants, the Johns Hopkins approach requires a donor half-match, meaning that either the parents or children of the patient could be donors. After three days, the patient is given a high dose of cyclophosphamide to allow the newly transplanted blood cells to take root. Ultimately, cyclophosphamide an immune suppressor, destroys blood cells that are part of the donor's immune system and spares the donor stem cells. Brodsky calls cyclophosphamide the "control-alt-delete to the immune system" because it acts as a reboot system. The drug prevents rejection of the transplant and stops the donor cells from attacking the patient which gives normal blood cells a chance to develop.

Newton may be free from sickle cell. But this bone transplant method is far from being risk or critic-free. Skeptics find the procedure too risky making note that most sickle cell patients won't die without a bone marrow transplant. Bone marrow transplants usually require the use of toxic chemicals to suppress the transplant recipient's own marrow. The toxicity of the chemicals is so harsh that adults with organ damage due to sickle cell probably would not survive the transplant.

The Johns Hopkins' method is less toxic. According to Dr. Brodsky, they only administer a suppressive dose for the immune system that not only prevents rejection of the bone marrow transplant but does it without causing further damage to organs. For sickle cell patients this method offers a promising alternative toward curing the disease.

Source: http://www.courant.com/news/health/hc-healthsicklecell.artapr22,0,3903868.story, http://www.sicklecelldisease.org/about_scd/index.phtml, http://www.associatedcontent.com/article/587253/hemoglobin_c.html