Magazine article Nutrition Health Review

Pioneering Bone Marrow Procedures

Magazine article Nutrition Health Review

Pioneering Bone Marrow Procedures

Article excerpt

Researchers at the University of Texas-Southwestern Medical Center at Dallas (UT) are helping to develop new procedures that may reduce infections and diseases resulting from bone-marrow transplants.

The work by Dr. Ellen Vitetta, director of the Cancer Immunobiology Center, and Dr. Robert Collins, director of the UT Southwestern Hematopoietic Cell Transplant Program, is part of research at UT Southwestern designed to identify the problem cells in a bone marrow transplant and eliminate them before the transplant is carried out. The latest findings appeared in the February 4, 2003 issue of the Proceedings of the National Academy of Sciences and online at the journal's Web site.

In a bone marrow transplant, the patient is treated with very high doses of chemotherapy, with or without radiation, to destroy cancer cells. This process also destroys the bone marrow, which is replaced with healthy marrow cells obtained either from the patient beforehand (autologous) or from a healthy donor (allogenic). Once transplanted, the donated bone-marrow cells multiply and repopulate the patient's blood cells.

Allogenic stem cell transplants are preferred for many hematologic malignancies or inherited disorders. While this type of transplant often has an anti-leukemic effect, the risk is graft-versus-host disease (GVHD), in which the donated immune system (the graft) begins to attack the recipient's body (the host).

If the graft T cells (lymphocytes) are depleted before transplantation, GVHD is eliminated. However, there is no anti-leukemic effect, and the patients are at risk for infection.

"Graft-versus-host disease--when T cells are not eliminated and infections when they are--causes significant morbidity and mortality in patients," said Vitetta, the study's senior author.

To combat this problem, Drs.Vitetta and Collins are developing and refining an in vitro procedure to activate the donor T cells responsible for causing GVHD. These activated T cells are then eliminated with an immunotoxin against the cellular activation marker, CD25. This removes the cells responsible for GVHD but spares cells responsible for the anti-leukemic activity and for fighting infections.

Immunotoxins are drugs created by linking an antibody to a portion of bacterial or plant toxin to destroy cells expressing the molecule to which the antibody binds.

"One of the major goals--the Holy Grail of bone marrow transplantation--is to separate graft-versus-host disease from graft-versus-leukemia, and we're still not sure it can be done. But, what we've seen so far is very encouraging. If this approach proves successful, it would make transplants a lot safer and more widely utilized," said Dr. Collins.

In a recent clinical study in France, Dr. Vitetta's group showed that the incidence of GVHD was greatly reduced in patients who were infused with the treated cells. …

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