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Select immune cells help marrow grafts

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9:35am, January 8, 2004
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From San Diego, at a meeting of the American Society of Hematology

By excising certain immune cells from donor bone marrow, physicians have devised a new and possibly more versatile way of performing marrow transplants.

These transplants give healthy, blood-producing cells to people with diseases such as leukemia. In optimal cases, a sibling or someone else with certain immunity genes nearly identical to a recipient's is available to donate marrow.

"But many people die for lack of a matched donor," says Andrea Velardi of the University of Perugia in Italy. When only mismatched marrow is available, the recipient's immune system must be temporarily knocked out so it won't attack the transplanted cells. Moreover, the immune cells from the donor's marrow need to be stripped out to prevent them from attacking the recipient's body, causing what's called graft-versus-host disease. Until the recipient's immune system recovers, he or she is excessively vulnerable to infection, making normally nonlethal pathogens potentially deadly.

To help these high-risk patients, Velardi and his colleagues extracted T cells, which are immune cells that target specific pathogens, from batches of donated marrow destined for genetically mismatched recipients. From the extracted cells, the doctors nurtured the growth of specific

T cells that fight Aspergillus fungi or cytomegalovirus, the two most-deadly microbes for transplant recipients. To avoid causing graft-host incompatibility, the researchers then discarded from the mix those T cells that reacted against cells from the intended marrow recipient.

The team injected the now-compatible disease-fighting T cells into each recipient 2 weeks after a marrow transplant. Of 10 transplant recipients who got T cells targeting Aspergillus and of 27 patients who got T cells for cytomegalovirus, none subsequently got sick from the targeted pathogen. Five people had already developed cytomegalovirus disease between receiving the transplant and the T cells, and two of these died. None of the T cell infusions caused graft-versus-host disease.

By contrast, 22 of 23 transplant patients who received processed, mismatched marrow, but not the selected T cells, developed symptoms caused by cytomegalovirus, and 5 died from the virus. Pneumonia from persistent Aspergillus infections affected 13 of these patients, killing 7 of them.

The procedure is expensive and time consuming, requiring doctors to cultivate T cells for individual microbial threats one at a time.

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