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Genetic Test Predicts Success of Bone-Marrow Transplant

By LabMedica International staff writers
Posted on 02 Mar 2017
Genetic mutations drive the pathogenesis of the myelodysplastic syndrome (MDS) and are closely associated with clinical phenotype and therefore, genetic mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation.

MDS is a blood disorder in which the bone marrow does not produce enough healthy blood cells. More...
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.

A large team of scientists collaborating with those at the Dana-Farber Cancer Institute analyzed blood cells from over 1,500 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. They performed targeted mutational analysis on samples obtained before transplantation and evaluated the association of mutations with transplantation outcomes, including overall survival, relapse, and death without relapse.

The scientists found that the most important predictor of patient prognosis was a mutation in the tumor protein p53 (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 investigators 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. The team 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.

Robert Coleman Lindsley, MD, PhD, the lead author of the study, said, “'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. 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.” The study was published on February 9, 2017, in The New England Journal of Medicine.


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