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Bone marrow transplant safe, effective for adult sickle cell patients: study

By Andrew M. Seaman

NEW YORK (Reuters) - Bone marrow transplants, which have already been used to cure sickle cell disease in children, may also hold promise for adults, according to a new study.

Using a less toxic bone marrow transplantation technique, researchers brought 26 out of 30 adult patients to a point where a majority of their blood cells were healthy and they could drastically reduce their pain and other medications.

“Many patients are not aware that there are curative options,” said Dr. John Tisdale. “When you’re a child, you can get a transplant and be reasonably well assured that the result will be good. Now we have data that for adults it will be the same.”

Tisdale is the study’s senior author and a senior investigator at the National Institutes of Health in Bethesda, Maryland.

Sickle cell disease is an inherited disorder that causes red blood cells to contain an abnormal protein, which makes them take on a sickle- or crescent-shape. These defective cells can block small blood vessels, leading to tissue damage or stroke.

Other complications of the disease are anemia, jaundice, gallstones, severe leg and arm pain and spleen, liver and kidney damage.

Approximately 100,000 Americans, primarily of African descent, have the disorder, which is most common in western Africa.

Tisdale said children had been considered better candidates for bone marrow transplants, because they can tolerate the more toxic procedure, which typically includes using radiation to get rid of the patient’s own bone marrow and chemotherapy to eliminate the immune system.

“What we decided to do was to try to figure out a way to do a bone marrow transplant that wasn’t so toxic and didn’t have so many side effects so we can apply it to adults with sickle cell disease,” he told Reuters Health.

Bone marrow contains the progenitor cells that manufacture the body’s blood cells, so the goal of a transplant is for the healthy donor marrow cells to become factories making blood cells free of the sickle cell trait.

For the procedure, the researchers used lower doses of radiation to make room for the new marrow, which was provided by a brother or sister who was a complete immune match to the patient. They also used a smaller dose of chemotherapy to only weaken the immune system, rather than destroy it.

The patients were between the ages of 16 and 65 years old and enrolled in the study between July 2004 and October 2013, according to the report in JAMA, the journal of the American Medical Association.

As of October 2013, the researchers write, 26 of the patients had successful transplants and none of them reported graft-vs-host disease, which happens when the implanted immune cells attack the patient’s own cells.

Those with successful grafts also reported no hospitalizations for a crippling pain condition that’s common and chronic throughout the life of someone with sickle cell disease.

“That’s huge,” Dr. Allison King said of the findings. “Just off the results of this study, the strict interpretation shows people with sickle cell disease with matched siblings should not have age held against them.”

King, of Washington University School of Medicine in St. Louis, Missouri, co-wrote an editorial published alongside the new study.

Of the few patients who rejected the donor graft, Tisdale said their own cells are allowed to repopulate their marrow – unlike transplants for cancers like leukemia.

“If they reject, then they get their sickle cell disease back,” he said. “While that’s a huge disappointment for the patient and us as well, it’s an additional safety feature of this kind of transplant.”

King said the biggest limitation with a procedure like this is that they used bone marrow that was a complete match from the patients’ siblings.

“Most patients don’t have fully matched siblings,” King said. “For those that do, I think these patients should be offered a transplant if they’re interested in it.”

Tisdale said they’re currently working on a study to explore whether partially matched bone marrow from relatives is also effective. That, he said, would make the procedure widely available. He added that there are already hospitals offering this procedure.

“We certainly feel that this technique should be considered for adult patients with severe complications of sickle cell disease,” he said.

SOURCE: http://bit.ly/VhUWJb and http://bit.ly/1pM0PMH JAMA, online July 1, 2014.

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