Wednesday, 28 September 2005 00:00

Marrow Transplant Technique May Help Blood Cancer Patients

WEDNESDAY, Sept. 28 (HealthDay News) -- A more focused approach to bone marrow transplant in patients with blood cancers dramatically lowered the incidence of graft versus host disease (GVHD) -- a potentially deadly complication of the procedure -- in a small group of patients, researchers report.

The approach has the potential to provide an easier alternative for people with leukemia, lymphoma and other related cancers, especially people over the age of 50, who typically have trouble withstanding conventional bone marrow transplantation procedures.

The findings appear in the Sept. 29 issue of the New England Journal of Medicine.

"We need replication in other studies but, if it is verified, it means there would be another approach to conditioning a patient that would greatly minimize acute GVHD but lead to the same beneficial effects," said Dr. Marshall Lichtman, executive vice president of research and medical programs for the Leukemia & Lymphoma Society.

Bone marrow transplants can cure some cases of leukemia, lymphoma and related blood cancers. The procedure is a severe one, however, and involves knocking out the patient's existing bone marrow with chemotherapy and/or radiation, then replacing the diseased blood stem cells with healthy stem cells from a donor.

People over the age of 50, in particular, have a hard time tolerating the standard form of transplantation, which can cause GVHD in about 50 percent of cases. In GVHD, the donor's immune cells attack the patient's body, causing intense diarrhea and severe rashes, among other things.

Recently, researchers have managed to show that, in mice, a less severe procedure had good results with fewer side effects.

Instead of receiving the blanket chemotherapy and radiation typical before bone marrow transplantation, the mice received radiation only to the lymph-node-bearing areas. They also received antithymocyte globulin, an immunosuppressive agent that destroys immune T-cells.

However, instead of destroying all of the patient's immune T-cells, this treatment selectively depleted just certain subsets of T-cells and allowed others, namely regulatory T-cells, to survive. The researchers explain that regulatory T-cells can hold attacking immune cells at bay.

"The regulatory T-cells are there in a high enough ratio to be able to shape and modify the donor immune cells to protect against GVHD, but still allow donor T-cells to mediate a graft anti-tumor effect," said study author Dr. Robert Lowsky, an assistant professor of medicine at Stanford University School of Medicine.

In other words, the donor T-cells attacked the tumor, but nothing else.

In the mouse study, regulatory T-cells went from a comprising 1 percent of total T-cells to more than 90 percent. The mice also had a significant reduction in acute GVHD.

The current study replicated that procedure in humans.

Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen starting with radiation to the lymph nodes only plus antithymocyte globulin, followed by a bone marrow transplant.

Only two of the patients developed acute GVHD and only one of those had "clinically significant" disease. In addition, patients with lymphoid malignant diseases who were in partial remission went into a complete remission.

Rates of chronic GVHD, a less serious form of the disorder, were no different, the researchers note.

"What these folks are saying is that if you use this conditioning regimen, you can get very good results and you eliminate or you greatly minimize acute GVHD," Lichtman said. "You keep the good effects while reducing the bad."

An accompanying editorial pointed out some caveats, however, including the small number of patients involved in the study and the inability to discern