Dr. Vivienne Rebel reports on a study of the relationship between gene mutations and overall survival after stem cell transplant | Aplastic Anemia and MDS International Foundation

Dr. Vivienne Rebel reports on a study of the relationship between gene mutations and overall survival after stem cell transplant

PubMed Abstract: 
Original Publication Date: 
Wednesday, October 1, 2014

Clinical parameters, such as blast counts and platelet counts, are important indicators of the severity of MDS and thus can help doctors decide on what treatment plan to follow.  Recent studies have shown that specific genetic abnormalities (e.g. mutations in genes called TP53, NRAS and Runx1) have similar predictive value.  The current study was undertaken to test whether specific gene mutations could also be used to identify patient group(s) that would benefit from a blood-stem cell transplantation.  This is an important question since the five-year survival rate of this type of intense therapy is only 40%.  

DNA samples, isolated from bone marrow or peripheral blood cells from 87 patients prior to undergoing a blood-stem cell transplant, were analyzed for genetic abnormalities.  Forty genes that are frequently affected in MDS cells were tested.  Patients were followed for a median of 49 months after their transplant.  Ninety-two percent of the DNA samples demonstrated mutations in one or more of the 40 selected genes.  Most importantly, this study found that mutations in genes called TP53, TET2 and DNMT3A are associated with decreased survival after a blood-stem cell transplant.  The three-year overall survival of patients with mutations in these genes was 19% versus 59% in patients without these mutations.  Of these three genes, TP53 was the most important predictor of survival after transplantation: median survival after transplantation for patients with this mutation was only 4.6 months and none lived much beyond 4 years.  Thus, it seems that a blood-stem cell transplant has minimal, if any, benefits for MDS patients with a TP53 mutation.  The authors conclude that if a blood-stem cell transplantation is being considered as a treatment option for a patient with MDS, the status of the TP53 gene (i.e., is it mutated or not) may be an important factor to consider.

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