Death after bone marrow transplant

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MunichA bone marrow transplant is often the last resort for people with blood cancer. But the procedure is risky: almost every second person does not survive it. A treatment approach that is as simple as it is effective could prevent this in the future.

A fatal side effect of a bone marrow transplant is that the donor's fresh immune cells attack not only cancer cells, but also healthy skin, intestinal and liver cells. "Graft-versus-host disease" (GHVD) is what doctors call the attacks by donor cells on healthy tissue. Now German and Swiss researchers have found out why this is the case - and how the catastrophe can possibly be prevented.

Delicate pretreatment

The routine preparation of patients seems to trigger a fatal chain reaction, found out Lars French from the University Hospital Zurich and Professor Robert Zeiser from the University of Freiburg.

Before a bone marrow transplant, the patient's diseased bone marrow and blood cells are killed. In their place, healthy donor cells should settle in the body. For this purpose, the sick are treated with gamma radiation, among other things.

Damage in the intestines

In experiments with mice, the scientists were able to show that this radiation also damages the intestines. This makes the intestinal wall more permeable for normally harmless bacteria that settle in the digestive tract. If they get deeper into the tissue, the intestine sounds the alarm: Among other things, it releases massive inflammatory messengers. And it is precisely these that call the donated immune cells onto the scene after the transplant.

Inflammatory substances attract immune cells

The messenger substance that triggers the inflammatory reactions is interleukin-1-beta, the researchers found. This protein also circulates in the blood during flu and febrile infections. It is released by specialized cells of the immune system in response to stimuli such as UV light, certain chemicals or pathogens.

Normally, interleukin-1-beta is in an inactive form in the body's cells. In order for it to be released, the messenger substance must first be armed. This is ensured by another protein in the cell, the so-called inflammasome.

Germ-free intestine

In their experiments, the researchers also succeeded in preventing fatal attacks on tissue: for example, mice with a germ-free intestine did not develop GHVD, even though they were irradiated and then received fresh blood stem cells. "This shows that a treatment of the digestive tract that kills the bacteria in the patient's intestine before the irradiation could prevent the deadly immune reaction," says study leader French.

Another possibility is to use an antibody to inhibit inflammasome and interleukin-1-beta. Even with mice treated in this way, the dreaded side effect did not occur.

"This means that a simple syringe with the antibody and an intestinal treatment could prevent most deaths after bone marrow donation," says French. The antibody against the inflammatory messengers even already exists. Further clinical studies in humans are now to follow. (Cf)

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