Sickle cell treated with bone marrow transplantation

Bone marrow transplantation appears to be the first treatment for sickle cell anemia with the potential to completely eradicate the disease in some patients, report researchers from Emory, the Fred Hutchinson Cancer Research Center and elsewhere in the Aug. 9 New England Journal of Medicine.

Nearly three-fourths of 22 children with severe sickle cell disease entered into a five-year study remain free of the disease an average of two years after transplantation. Between 1991 and 1995, the children aged 3 to 14 each received bone marrow from a sibling with the same type of marrow.

"This study determines that bone marrow transplantation is curative therapy for children with severe sickle cell disease," said James Eckman, a co-author of the paper and director of Emory's sickle cell program. "Transplantation can be done with acceptable complications. Finally, we can offer some patients hope for a cure."

Twenty of the study participants are surviving and 16 show no symptoms of sickle cell disease, including two children who received transplants from the Bone Marrow Transplant Service at Egleston Children's Hospital.

"The 10-percent death rate and potential for long-term complications of bone marrow transplant meant that this therapy should be reserved for the 25 percent to 30 percent of children who will have severe complications of sickle cell disease," said Eckman, professor of medicine (hematology-oncology) at Emory.

The multicenter effort was partly funded by the National Heart, Lung and Blood Institute of the National Institutes of Health.

"This study proves that sickle cell anemia can be cured with bone marrow transplantation," said Roger Vega, who performed the transplantations on the two children at Egleston. Vega is associate professor of pediatrics (hematology/ oncology) at Emory. "The challenge we face from now on is to find alternative sources of bone marrow, because not all patients needing a transplant have a suitable donor. The other challenge is to identify patients who are at high risk for life-threatening events and offer bone marrow transplantation before these events occur. The two patients we transplanted at Egleston are doing very well and both have minimal sequela from their strokes."

The study has been extended for five more years and is now open to young adults. For information, call (404) 616-3572.

Current research conducted by sickle cell anemia experts at the School of Medicine is supported by a $7.5-million grant from the National Institutes of Health.

"Without a doubt, early detection and treatment of sickle cell anemia has dramatically improved the length and quality of life of children with this disease," said Eckman, principal investigator of the NIH grant. "Still, we believe much more can be done to treat the painful manifestations of this childhood disease."

Past and ongoing sickle cell research at Emory has included clinical studies of analgesic agents for alleviating acute pain, transfusion therapy for neurologic and surgical complications, and the use of hydroxyurea for chemotherapy. In addition to bone marrow transplantation, research with the NIH grant includes the following:

Blood flow
A variety of researchers at Emory and Georgia Tech are investigating ways to prevent the adhesion of sickle cells to blood vessel walls. This adhesion plagues patients in two ways: first, it clogs vessels and keeps blood from properly nourishing tissue. Blood-starved tissue, called ischemia, can cause severe pain and organ damage. A goal of the Center's research is to eventually develop ways to inhibit sickle cell adhesion in patients in the beginning stages of a pain crisis.

Secondly, adhesion may play a major role in acute chest syndrome--a sudden and severe inflammation of the lungs and a common manifestation of sickle cell disease. Sickle cells may stimulate the cells lining blood vessels in the lungs to express adhesion receptors, leading to acute inflammation and lung damage.

Clot-promoting properties
Eckman and his colleagues believe that once cells begin to sickle and damage endothelial cells, they release factors that activate platelets in the blood, leading to clotting. They are looking at the effects of fish oil (dietary omega-3 fatty acids) supplements, which have been shown in non-human primates to stop blood clot formation at sites of vessel injury.

Chronic organ damage
As patients with sickle cell disease live longer due to early and careful management, physicians must deal with problems resulting from chronic organ damage. Renal failure is becoming an important cause of death in older sickle cell patients. Early on, patients with renal problems have protein in the urine, which later progresses to a more severe decrease in renal function, sometimes requiring dialysis. Kidney experts are studying how the kidneys filter protein, how damage occurs, and how signs of early kidney disease may be recognized.

--Lorri Preston

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