Stem Cell Transplants Suggest 'Cure' for Severe Sickle Cell Disease

December 10, 2002

Jane Salodof MacNeil

Dec. 10, 2002 (Philadelphia) - French researchers are talking about a potential cure for sickle cell disease after reporting an 85% disease-free survival rate for 69 children treated with stem cell transplants from sibling donors.

All but six of the children are alive. Younger children fared better than older children. Among children aged 15 years and younger who received one of two conditioning regimens tested in the study, 90% are disease-free.

The regimen has so improved during the 14 years since the study began that lead investigator Francoise Bernaudin, MD, of Saint Louis Hospital in Paris, France, and Hospital Saint-Justine in Montreal, Quebec, yesterday reported, "There have been no deaths among the last 30 transplants."

Dr. Bernaudin presented results from the 14-center trial at the American Society of Hematology (ASH) annual meeting here. All of the children had severe sickle cell disease and were deemed at high risk for life-threatening complications of their disorder.

At a median follow-up of 36 months, 91.3% of the children were alive, and 84.1% were event-free. In 27 of 29 children who were observed after a median follow-up of 62 months, no strokes had occurred and clinical improvement in splenic function was seen along with a decrease in disease-related osteonecrosis.

Despite the risks associated with transplantation, Dr. Bernaudin reported that short-term toxicity was very limited. Complications related to graft versus host disease (GVHD) caused four of the deaths. The fifth child died of sepsis, and the sixth died of stroke.

Initially, the investigators tested a conditioning regimen of busulfan and cyclophosamide. After 12 cases, they added rabbit anti-thymocyte globulin (ATG) to the regimen.

In 60 cases, bone marrow was used for the stem cell transplant. Cord blood was used in seven cases, a combination of cord blood and bone marrow in one case, and peripheral blood stem cells in another.

Dr. Bernaudin urged parents of children with sickle cell disease to preserve blood from the umbilical cords of latter-born children in case transplantation becomes necessary for the older, sicker child. She said her clinic now offers to help parents preserve cord blood.

From time of diagnosis, it begins to prepare parents for the possibility that children with the disease may eventually need transplantation, she said. Early identification of patients at high risk for sickle cell disease-related complications was a key factor in the protocol's success, according to Dr. Bernaudin.

"The side effects are minimal and the fact that we can use the word 'cure' suggests significant progress toward this terrible disease," she said in a prepared statement that also highlighted the conditioning regimen and the use of sibling donors.

More work needs to be done to reduce GVHD and identify high-risk candidates for transplantation, she and her colleagues concluded.

Even though younger children fare better with transplantation, the treatment is still a difficult choice for parents, according to ASH president-elect Ronald Hoffman, MD, of Harvard University in Boston, Massachusetts. "We have been reluctant to expose children to the risk of stem cell transplant," he said, citing high mortality rates.

"The dilemma is you have a chronic illness where people are going to live into their 40s and 50s," Dr. Hoffman said, predicting that the study could change the way people are treated for sickle cell disease. "With the regimen they are trying to develop, that risk might be merited," he said.

ASH 44th Annual Meeting: Abstract 4. Presented Dec. 8, 2002.

Reviewed by Gary D. Vogin, MD

Jane Salodof MacNeil is a freelance writer for Medscape.


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