Although children with sickle cell disease have benefited from the emergence of improved therapies, options for adults with the disorder have lagged and many die in their early 40s. New evidence published today in JAMA suggests that a less toxic bone marrow transplant technique may provide adults with a new option.
Sickle cell disease is caused by a genetic variation that results in the production of sickle-shaped blood cells. These cells can clump together, causing blockages in blood vessels, severe pain, and even stroke. Over time, damage to multiple organs can occur. Blood transfusions, prophylactic antibiotic therapies, and other interventions help manage patients’ symptoms, but only bone marrow transplantation can cure the disease. Although about 400 children have received such transplants to date, adults are less able to tolerate this potentially curative treatment, which involves completely destroying the patient’s own bone marrow and replacing it with marrow cells from a compatible donor.
John F. Tisdale, MD, senior investigator at the National Institutes of Health, and his colleagues found that a less drastic technique for bone marrow transplantation may be a better option for adults. Instead of using radiation to completely eliminate the patient’s own bone marrow before transplant, Tisdale and colleagues reduced the patient’s bone marrow by half. After transplant, the patient has bone marrow containing a mix of his or her own marrow cells and the donor’s marrow cells.
The researchers tested their technique in 30 patients aged 16 years to 65 years. One patient died after a relapse to sickle cell, but 29 survived for an average of 3.4 years without relapse. In 26 patients, the donor cells engrafted without an autoimmune reaction, and 15 were able to discontinue immunosuppressive treatment. Treated patients also required fewer sickle cell–related hospitalizations.
Tisdale discussed the findings with news@JAMA.
news@JAMA: Why did you decide to do the study?
Dr Tisdale: Adults with sickle cell disease not only have a difficult life, with pain and organ damage, but they die early. Despite progress in supportive care, the median age at death for patients with sickle cell remains the early 40s. That hasn’t changed in decades.
news@JAMA: Why hasn’t bone marrow transplantation been as successful for adults as it has for children?
Dr Tisdale: Bone marrow transplant, like most medical therapy, is easier for children to undergo. They tolerate chemotherapy, radiation, and bone marrow transplants better because they have more reserve. Adults tolerate it less well. The older you are the worse you’ll do with a transplant.
news@JAMA: Why don’t all children with sickle cell disease receive bone marrow transplants?
Dr Tisdale: The first bone marrow transplant was in a kid with sickle cell and leukemia. The child had a life-threatening illness and the only cure was bone marrow transplantation. The child was cured of the leukemia and sickle cell. It was next tried in kids with sickle cell who’d had a stroke.
It’s generally reserved for children with sickle cell who have some indication they are not doing well. Children do pretty well with sickle cell, so you don’t want to do something as harsh as a bone marrow transplant to a child who is doing well. There is also some resistance from families because high doses of radiation render the children sterile. Some think it’s better to wait until these children are adults and let them decide.
news@JAMA: How is your approach different?
Dr Tisdale: We tried to make bone marrow transplant safer so it wasn’t such a big trade-off for adults. It’s different in 2 fundamental ways. It doesn’t completely destroy the marrow. In a standard transplant, if the transplant doesn’t “take,” the patient dies because they can’t recover bone marrow. If our strategy doesn’t work, the patient’s own bone marrow comes back and they go back to having sickle cell. We also were striving for [immune] tolerance between donor and recipient.
news@JAMA: What are the next questions you need to answer?
Dr Tisdale: Our next big question is, can we extend this to more patients by loosening the criteria for the donor? What if it required a half match rather than full match? Most patients don’t have a full-match sibling. But virtually everyone has a half match—parents, sibling, or child.
news@JAMA: What’s the main take-home message?
Dr Tisdale: Adult patients with sickle cell and their care providers should consider whether a transplant is an option.