A better bone marrow transplant: preventing graft-versus-host disease

Bone marrow transplant is a key treatment for patients with leukemia, lymphoma, multiple myeloma and other blood disorders.

University of Michigan (U-M) researchers have discovered that inhibiting a signalling pathway in some of the transplanted cells could prevent the most serious potential complications of the procedure, a conflict between the transplanted cells and the recipient's own tissue called graft-versus-host disease.

In a paper scheduled to be published online in the Journal of Clinical Investigation on March 1, Dr. Ivan Maillard, a faculty member at the U-M Life Sciences Institute, explains how a cell-to-cell communication pathway known as Notch signalling plays a critical role in graft-versus-host disease and details how antibodies inhibiting specific elements of the Notch pathway can prevent graft-versus-host disease in mice - without serious side effects and without substantially compromising the cancer-fighting ability of the transplanted cells.

After bone marrow transplant, donor stem cells replace the patient's depleted or dysfunctional stem cells. Once established in the patient, the donor cells begin to make healthy red and white blood cells. At the same time, donor immune cells called T cells can recognise and destroy tumour cells in the patient, which is the main beneficial effect of the procedure in cancer patients.

However, in graft-versus-host disease, the donor T cells also recognise the recipient's normal tissues as foreign and begin to attack organs like the intestine, liver, lungs and skin.

"This can lead to severe, life-threatening damage," Maillard said.