"Conditioning" Key to Curing Sickle Cell Disease

The key to beating sickle cell disease, is conditioning, although not the sort of regimen associated with physical fitness. Reduced-intensity conditioning (RIC), involving use of immunosuppressive drug therapies, has been found to be safe and effective in preparing stricken children for curative bone marrow transplants. A researcher at Children’s Hospital of Pittsburgh of UPMC has pioneered this treatment, which offers fresh hope to children suffering from the painful and debilitating effects of sickle cell disease.

Lakshmanan Krishnamurti, MD, a pediatric hematologist/oncologist at Children’s Hospital, helped develop a form of bone marrow transplantation that relies on reduced-intensity conditioning (RIC) prior to surgery. RIC regimens are less toxic for patients with severe sickle cell disease because they eliminate life-threatening side effects generally associated with conventional bone marrow transplantation.

Lakshmanan Krishnamurti, MD, visits with Keyshawn Johnson, one of his patients, along with Krista Burgbacher, a child life specialist. (Photo Courtesy of Justin Merriman, Tribune-Review)

“Bone marrow transplant is the only known cure for sickle cell disease. But doctors have avoided performing them in these patients because complications from a traditional bone marrow transplant can be life-threatening,” said Dr. Krishnamurti, who is also the director of the Sickle Cell Program at Children’s.

The traditional approach calls for heavy doses of chemotherapy before transplant to destroy the recipient’s existing marrow so it will not reject the donated marrow. But with their marrow destroyed, transplant recipients become vulnerable to life-threatening complications, a risk viewed as unnecessary because sickle cell disease is not typically immediately life-threatening. However, Dr. Krishnamurti’s RIC procedure uses large doses of immunosuppressive drugs before transplant, rather than high doses of chemotherapy. The less-toxic approach will open the door to bone marrow transplants to greater numbers of pediatric sickle cell disease sufferers.

“Through the reduced-intensity approach we developed, the potential for complications is dramatically lessened. This study offers hope for a cure to thousands of patients with severe sickle cell disease.”

What is Sickle Cell Disease?
A hereditary blood disorder in which O-shaped red blood cells (left) take on a crescent shape (right), sickle cell disease afflicts an estimated 80,000 people in the United States. It is characterized by defective hemoglobin, a protein in red blood cells that carries oxygen to the body. Blood cells affected by sickle cell disease are stiff and sticky and form into the shape of a C when they lose their oxygen. They tend to cluster, causing blockages that stop the movement of healthy, normal oxygen-carrying blood. This can cause excruciating pain; strokes; damage to organs including the heart, kidneys and lungs; and a shortened life expectancy. It affects primarily blacks, including 250,000 in western Pennsylvania. Children’s Hospital currently sees about 250 pediatric patients with sickle cell disease.

A Decade Committed to the Cure
While at the University of Minnesota in 1999, Dr. Krishnamurti was the first physician in the world to perform a reduced-intensity bone marrow transplant in a patient with sickle cell disease. He joined Children’s Hospital in 2003 and that year performed the region’s first successful bone marrow transplant in a patient with sickle cell disease. Austin Jones, then 5, of Indiana, Pa., underwent RIC, with donor marrow from his brother, Anthony Jr. Today, Austin is free of the disease.

Dr. Krishnamurti and colleagues reported in the November 2008 issue of Biology of Blood and Marrow Transplantation that RIC has proven to be the only safe and effective cure for sickle cell disease. The article discussed how six of seven sickle cell patients who received RIC bone marrow transplants in the last decade now have donor marrow and are free from symptoms of their sickle cell disease. Dr. Krishnamurti led five of the seven transplants in the study.

Last Update
January 7, 2014
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Last Update
January 7, 2014