A previously incurable blood disorder – sickle-cell disease – has been successfully treated in 9 of 10 adults who received stem cells transplanted from tissue-matched siblings.

The inherited disease causes the bone marrow to churn out blood cells that are shaped like crescents, or sickles, rather than the round shape of healthy cells. This causes painful blockages in blood vessels, depletion of blood and severe anaemia.

Transplants have worked well in around 200 children but don’t succeed in adults because the technique requires that cells in the recipient’s own bone marrow are destroyed first – children can usually tolerate this, but adults can’t.

Even when adults have got past this obstacle, they have gone on to develop the fatal condition graft-versus-host disease (GVHD), in which the donated cells attack and destroy other tissue.


Mild destruction

Now John Tisdale of the US National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, and colleagues have overcome both problems in adults.

Instead of using the powerful drugs given to children to destroy all the native cells in their bone marrows, Tisdale’s team mildly irradiated the whole bodies of 10 adults with sickle-cell disease to “make room” in their bone marrow.

Starting about a week before the transplant, the patients also received a drug called alemtuzumab which destroyed circulating native white blood cells so they couldn’t attack the transplanted cells.

The donated cells came from siblings, and the researchers extracted and transplanted very specific CD34 blood stem cells, which grow into all blood types.

Mixed blood

After the transplants, the patients’ blood was a mixture of donated and native cells. The treatment completely prevented further production of the offending sickle-shaped blood cells in nine of the patients.

Also, haemoglobin levels rose from 9 to 12 grams per decilitre of blood in these patients, overcoming anaemia.

As an additional precaution to prevent GVHD, patients received the anti-rejection drug rapamycin, which stimulates production of T-helper and regulatory T-cells, which dampen immune aggression by both native and transplanted cells.

“The simplicity, low toxicity and high efficacy of this approach make it feasible for use at most transplantation centres,” the researchers conclude.

Not where it’s needed

“It’s very real step forward in the treatment of sickle-cell disease,” says Chris Mason, a senior stem cell researcher at University College London. “If you have a good intensive care facility, you would be able to do this.”

However, because of the need for intensive care immediately following the operation, it may not reach poorer areas of the world where the disease is common, such as sub-Saharan Africa, says Mason.

Another challenge is finding siblings or unrelated donors with matching blood types, which is not always feasible. One option in future may be to create stem cells from a patient’s own tissue, then return these after using gene therapy to correct the genetic mutation that causes sickle-cell disease.

This has been done successfully in mice with sickle-cell disease, but will not be possible for some years in people.

Gene therapies are another option: these might restore sickle-shaped cells to normal.

Journal reference: New England Journal of Medicine, vol 361, p 2309