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Study offers hope for deadly side effect of bone marrow transplants

Researchers have found promising signs that an immune system protein could protect the gut and prevent some of the potentially deadly side effects of bone marrow transplantation performed for blood cancer.

Bone marrow transplants can cure blood cancers like leukaemia and lymphoma. However, in up to 70 per cent of recipients, the transplant causes a potentially deadly complication of graft-versus-host disease (GVHD), where the donor’s immune cells attack the host’s tissues, including the skin, gut and lungs.

The study in mice found the immune protein Interferon-Lambda – also known as IL-29 –strengthened the gut lining and helped prevent the gut damage often caused by bone marrow transplants and GVHD.

The researchers hope IL-29 could also help prevent the gut damage caused by other conditions like inflammatory bowel disease.

The study has been published in the prestigious journal Blood. It was led by the head of QIMR Berghofer’s Immunopathology Laboratory, Dr Kate Gartlan, and Professor Geoff Hill, who is now based at the Fred Hutchinson Cancer Research Center in Seattle.

Dr Gartlan said they discovered a new way in which IL-29 works to prevent the gut damage.

“We found that IL-29 – a cytokine, or protein that occurs naturally in the immune system – acts on stem cells in the gut to boost their function,” Dr Gartlan said.

“Stem cells are needed to regenerate the gut after damage. So by giving IL-29 to mice, it strengthened their gut.

“Those mice later had better outcomes after bone marrow transplants because the IL-29 protected them from the inflammation we usually see.

“This is the first time anyone has identified the way in which Interferon-Lambda works on gut stem cells to protect them from damage.

“We can’t say yet that interferon-lambda will definitely have the same effect in humans, but these early results in mice are promising.”

QIMR Berghofer researcher and Royal Brisbane and Women’s Hospital transplant physician Dr Andrea Henden said the team hoped IL-29 could become a new preventative option for GVHD.

“Graft-versus-host disease is a terrible complication of bone marrow transplantation, especially when it involves the gut,” Dr Henden said.

“At the moment, there are limited effective treatments available, so we desperately need new options to prevent this often fatal disease.

“Interferon-Lambda is already available as a drug for other diseases, so we hope to also start testing it in patients with gut damage and inflammation.

“If we could make bone marrow transplantation safer, then we could use it to treat more patients with blood cancer. Hopefully, we could also reduce the use of toxic drugs in patients who develop GVHD.

“Our findings also suggest that Interferon-Lambda could help prevent the gut inflammation that occurs in other disorders like inflammatory bowel disease and Crohn’s. As a next step, we also hope to test whether this is the case.”

The study was funded by the National Health and Medical Research Council and the Leukaemia Foundation.