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Genetic test predicts success of bone-marrow transplant

13 February 2017
Appeared in BioNews 888

A new blood test can predict how well patients with myelodysplastic syndrome (MDS) will respond to bone-marrow transplants.

MDS is a blood disorder in which the bone marrow doesn't produce enough healthy blood cells. Typical treatments include high- or low-intensity 'conditioning' therapy (such as radiotherapy or chemotherapy), and donor stem cell transplants for patients with high risk of mortality. However, many patients can experience relapse or severe complications.

'Although donor stem-cell transplantation is the only curative therapy for MDS, many patients die after transplantation, largely due to relapse of the disease or complications relating to the transplant itself,' said the study's lead author, Dr Robert Coleman Lindsley of the Dana-Farber Cancer Institute in Boston, Massachusetts. 'As physicians, one of our major challenges is to be able to predict which patients are most likely to benefit from a transplant.'

In the study, published in the New England Journal of Medicine, the researchers analysed blood cells from over 1500 MDS patients, combined with clinical information such as age and disease status. They were able to devise a genetic profile of mutations associated with poorer patient outcomes after transplantation.

Researchers found that the most important predictor of patient prognosis was a mutation in the TP53 gene. These patients tended to relapse sooner and survive for a shorter time after transplant. Whether patients had high- or low-intensity conditioning therapy before the transplant did not affect the outcome.

Specific mutations in other genes were also linked to poorer outcomes in older patients, although only when they received low-intensity conditioning therapy. The researchers suggested that these patients may benefit from high-intensity conditioning therapy to reduce the risk.

In young adults, one in 25 patients with MDS were found to have mutations associated with the rare, inherited Shwachman-Diamond syndrome, which affects the bone marrow, pancreas and skeletal system. Most of these patients were previously undiagnosed. Researchers found that each of these patients had acquired a TP53 mutation, indicating how MDS develops in these patients and giving insight into their poor prognosis.

'In deciding whether a stem-cell transplant is appropriate for a patient with MDS, it's always necessary to balance the potential benefit with the risk of complications,' said Dr Lindsley. 'Our findings offer physicians a guide – based on the genetic profile of the disease and certain clinical factors – to identifying patients for whom a transplant is appropriate, and the intensity of treatment most likely to be effective.'

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