MARROW TRANSPLANTS SHOWN TO CURE SICKLE CELL DISEASE.

Byline: Warren E. Leary The New York Times

A major international study has shown that bone marrow transplants can cure sickle cell disease in some children, a finding that experts say could herald a new era in treating the inherited blood disease.

Researchers involved in the study said they had achieved the cure in 16 of 22 patients with advanced disease by replacing the bone marrow that produces the defective red blood cells characteristic of the disease. But two of the children died after undergoing transplants.

Sickle cell disease is a family of inherited and previously incurable disorders that afflict several million people around the world. The disease is most common among people whose ancestors came from Africa, the Middle East, the Mediterranean or India. In this country, the condition primarily afflicts an estimated 80,000 African Americans, and 1 in 12 African American babies is born with a genetic tendency for passing on the disease.

In its worst form, the disease can result in severe episodes of pain in various part of the body, stroke, damage to internal organs and death. Current treatments, which can only relieve symptoms, include blood transfusions, pain killers and other drugs.

Although the study involved only children under age 14 who received donated marrow from siblings with highly compatible tissue, researchers said they hoped for a cautious expansion of the therapy to a wider range of patients.

Experts said bone marrow transplants were risky procedures that carried a 10 percent risk of death under the best of circumstances. This risk - along with complications from the operation, including infertility resulting from drugs used to destroy the old, defective bone marrow - means that the treatment cannot be considered for all sickle cell patients, the experts said.

The study, being published today in The New England Journal of Medicine, is significant because it proves, in a well-designed trial, that marrow transplants can cure sickle cell disease, as other smaller studies had indicated. And finding a way to cure even a small percentage of sickle cell cases is a major development, specialists said.

``Our findings indicate that bone marrow transplantation can cure sickle cell disease in a significant number of patients with advanced disease,'' said Dr. Keith Sullivan of the Fred Hutchinson Cancer Research Center in Seattle, the lead author of the study. ``In the paper, we used the word `curative' with a great degree of consideration and careful look at the data.''

The trial lasted five years, from 1991 through 1995, and involved 22 children who received marrow transplants at more than 30 centers in the United States, Canada, Europe and Brazil. After an average follow-up of two years, 20 of the patients survived. Of the survivors, 16 showed no symptoms of sickle cell disease. And 4 patients, or 18 percent, rejected the donor tissue and their sickle cell symptoms returned, the report states.

The study involved patients with advanced symptoms of sickle cell disease, including stroke, lung complications and organ impairment, who had a compatible sibling as a marrow donor.

While only about 7 percent of sickle cell patients meet the criteria of the study, the researchers said, further research should expand use of the procedure to more patients who are in danger of severe complications as the disease progresses.

Sickle cell disease describes a group of inherited disorders, including sickle cell anemia and sickle B-thalassemia. The disorders involve the body producing abnormal forms of hemoglobin, the oxygen-carrying component of red blood cells. With the disease, red blood cells, which are produced by bone marrow, periodically stiffen and take on irregular shapes that block small blood vessels and cause vascular inflammation.

For treatment, many adults also take hydroxyurea, an anti-cancer drug that causes the body to make types of hemoglobin that do not stiffen as readily, resulting in fewer complications for some patients.

``This is an exciting development in sickle cell treatment,'' said Dr. George Dover, a sickle cell specialist at the Johns Hopkins Medical Institutions in Baltimore.

``This work helps us define the risks and benefits of trying bone marrow transplants versus some of the more conventional therapies we have now, and new therapies that should be coming out in three or four years.''

Dover said new drug therapy for sickle cell, including wider use of hydroxyurea in the last year, and the better control of infections and other complications of the disease had increased both the life span and the quality of life for many sickle cell patients with fewer risks than marrow transplants.

``In patients who have shown severe complications, it is now reasonable to consider bone marrow transplants as an option,'' Dover said in an interview.