Bone Marrow Transplants May Cure Sickle Cell in Adults
WEDNESDAY, Dec. 9 -- Researchers say that a new method of bone marrow transplantation cured nine out of 10 adult patients with sickle cell disease, an inherited condition that causes bouts of severe pain, organ damage and sharply limits life expectancy.
Adults have typically not been candidates because they were thought to be too sick to handle the high doses of chemotherapy and radiation necessary to prep the body for the procedure, explained senior study author Dr. John Tisdale, a senior investigator in the molecular and clinical hematology branch at the U.S. National Institutes of Health.
Until now, transplantation was generally reserved for more resilient children, whose bodies had not yet suffered as much damage from sickle cell disease.
But the new method allows for a less grueling pre-transplantation routine, one that even adults with severe sickle cell can tolerate.
More than 70,000 Americans suffer from sickle cell disease, and it is especially common among blacks. People with the disease have abnormal, crescent-shaped hemoglobin. The abnormal cells have difficulty passing through small blood vessels, causing blockages and damaging tissues. Over time, the damage can lead to stroke and severe bouts of pain in the chest, arms, legs, chest and abdomen. Sickle cell disease also damages the kidneys, liver and spleen, leaving people, especially children, more susceptible to infection, said Dr. Lanetta Jordan, chief medical officer for the Sickle Cell Disease Association of America.
Treatments include prophylactic antibiotics to fight infections, blood transfusions and hydroxyurea, the only drug U.S. Food and Drug Administration-approved drug for treating sickle cell, Jordan said.
In the new study, Tisdale and his colleagues gave 10 patients ages 16 to 45 with severe sickle cell disease alemtuzumab, a drug used to suppress immune system T-cells; relatively low doses of radiation; and sirolimus, an immune suppressant to fight rejection. Marrow donors were siblings with matched HLA (human leukocyte antigen) markers in their blood.
None of the patients experienced graft-versus-host disease, one of the most common and potentially fatal complications of bone marrow transplants, in which the body rejects the new bone marrow.
After 30 months, all of them are alive, and nine of the patients had successful grafts and are considered cured of sickle cell disease, according to the study.
"It's been transforming for these patients," Tisdale said. "These were the sickest of the sick patients. Some were in the hospital every other week for pain or other crises. Today, some have gone back to school and to work. One patient had a baby."
The last item is important, because in conventional bone marrow transplants, high doses of chemotherapy drugs and radiation typically destroy fertility. However, the lower level of radiation used in the new method does not seem to do this.
The study is published in the Dec. 10 issue of the New England Journal of Medicine.
Conventional bone marrow transplants cure sickle cell disease by first using chemotherapy and radiation to wipe out the person's own marrow, which makes the faulty red blood cells. The marrow is replaced with stem cells from a donor's marrow, which then takes over and begins to produce new, healthy red blood cells.
But when doing the new bone marrow transplants, the researchers noted that not all of the patient's own marrow was wiped out. Some remained and seemed to co-exist with the donor marrow without causing problems, Tisdale said.
"That meant we didn't necessarily have to kill the entire bone marrow of the patient to make this work," Tisdale said, opening the possibility of using an even less toxic means of preparing the body for transplant.
Though most patients in the study are still taking immune-suppressant drugs, researchers hope to eventually wean them off the medications.
Dr. Miguel Abboud, a pediatric hematology/oncology specialist and a professor of pediatrics at the American University of Beirut Medial Center, in Lebanon, said the new protocol is promising, especially since it could eventually include those who don't have an HLA-matched sibling.
"The findings are very significant because adults with very severe sickle cell disease have decreased life expectancy and multiple morbidities but have limited therapeutic options," said Abboud, who wrote an accompanying editorial. "In the past these patients were excluded from transplant studies as they are very poor candidates for high dose chemotherapy regimens. This study makes it possible to offer this subset of patients with severe sickle cell disease stem cell transplants."
Dr. Lakshmanan Krishnamurti, a pediatric hematologist/oncologist at the University of Pittsburgh and director of the Sickle Cell Program at Children's Hospital of Pittsburgh, has done bone marrow transplants in children, also using a less toxic protocol.
"This is an important paper and a big step forward for the field," Krishnamurti said. "Now we are able to say, 'OK, young adults or not so young adults can be transplanted successfully.' That is a very big deal."
There's more on sickle cell disease at the Sickle Cell Disease Association of America.
Posted: December 2009