Persistent Disease–Associated Mutations Linked to Higher Myelodysplastic Syndrome Progression After Treatment

By David Costill
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Myelodysplastic Syndrome patients with persistent disease–associated mutations are at a higher risk for disease progression compared with patients who do not have these mutations, according to a recent study in the New England Journal of Medicine.

“Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for patients with myelodysplastic syndrome,” Eric J. Duncavage, MD, of the division of pathology & immunology at the Washington University School of Medicine in St. Louis, and colleagues explained. They also noted that until the present study, “the molecular predictors of disease progression after transplantation are unclear.”


Gene mutation. Max Pixel.

Duncavage and colleagues studied the bone marrow and skin samples of 90 patients with myelodysplastic syndrome. Each study patient also underwent treatment for myelodysplastic syndrome, including allogeneic hematopoietic stem-cell transplantation after a myeloablative or reduced-intensity conditioning regimen.

They genotyped mutations using error-corrected sequencing before stem cell transplantation and 30 days after treatment.

Study results showed that of the 90 patients, 86 presented with at least one validated somatic mutation when examined before treatment. Further, 30 days after treatment, 32 patients presented with at least one mutation with a maximum variant allele frequency of at least 0.5%.

The researchers determined that patients with disease progression had mutations with higher maximum variant allele frequency when examined after treatment. They determined that having at least one mutation with a variant allele frequency of at least 0.5%, after treatment, was linked to a higher risk of disease progression (P < .001).

Comparative analysis also showed that patients with a mutation with a variant allele frequency of at least 0.5% after treatment had higher risk of progression and reduced 1-year survival, compared with patients who did not (P = .002).

“The risk of disease progression was higher among patients with myelodysplastic syndrome in whom persistent disease–associated mutations were detected in the bone marrow 30 days after transplantation than among those in whom these mutations were not detected,” Duncavage and colleagues concluded.