Dec. 9, 2009 - A gentler form of blood stem cell transplant can reverse severe sickle cell disease in adults lucky enough to find a matched donor.
Patients with sickle cell disease have a genetic mutation that results in defective crescent-shaped red blood cells. Severe disease causes stroke, severe pain, and often fatal damage to major organs.
Blood stem cell transplants have reversed sickle cell disease in some 200 children. But the procedure, which requires destruction of the patients' defective cells by radiation and chemotherapy to make room for the transplanted cells -- is too intense for adults weakened by sickle cell disease.
Moreover, adult patients are more prone to deadly graft-versus-host disease (GVHD), in which the transplanted cells attack the recipient.
But recent studies show that in some stem cell transplant recipients, some host cells survive the toxic "conditioning regimen" of radiation and drugs -- and their progeny happily coexist with those of the transplanted stem cells.
If this could be done on purpose, the treatment could be made less intense. That's exactly what National Institutes of Health researcher Matthew M. Hsieh, MD, and colleagues set out to do. They used low-dose radiation to create space for the new cells and used an immune-suppressing drug called sirolimus to prevent GVHD.
Over five years, they found matched blood stem cell donors for 24 of 112 patients suffering severe sickle cell disease. So far, 10 of the patients have undergone the mini-transplant treatment.
Nine of the patients had their sickle cell disease reversed; none died and none suffered GVHD.
"The simplicity, low toxicity, and high efficacy of this approach make it feasible for use at most transplantation centers," Hsieh and colleagues conclude.
It's not yet clear whether it will be possible to wean the patients from immune-suppressing treatment, which puts them at risk of life-threatening infections, notes Miguel R. Abboud, MD, of the American University of Beirut, Lebanon, in an editorial accompanying the Hsieh study.
"If immunosuppressive therapy can be safely withdrawn, this regimen could become an option for young, asymptomatic patients with sickle cell disease," Abboud suggests.
And of course, the technique can only be used on the minority of patients who have a sibling that can donate matched stem cells.
The Hsieh study, and the Abboud editorial, appear in the Dec. 10 issue of the New England Journal of Medicine.