Mutations After Transplant in Myelodysplastic Syndrome May Correlate With Progressed Disease

Share this content:
The presence of persistent disease-related mutations 30 days after ASCT for myelodysplastic syndrome was associated with higher risk of disease progression.
The presence of persistent disease-related mutations 30 days after ASCT for myelodysplastic syndrome was associated with higher risk of disease progression.

The risk of disease progression was greater in patients with myelodysplastic syndrome (MDS) who had disease-related mutations that persisted 30 days after transplantation for treatment of MDS than in patients without persistent disease-related mutations, according to a recent exploratory analysis in the New England Journal of Medicine.

Allogeneic hematopoietic stem-cell transplantation (ASCT) remains the only curative therapy for patients with MDS, though the molecular predictors of post-transplantation disease progression have not been well established. To address this, researchers sequenced bone marrow and skin samples from 90 patients with MDS who underwent a myeloablative or reduced-intensity conditioning regimen followed by ASCT. Researchers next assessed mutation clearance via error-corrected sequencing to classify mutations from bone marrow samples 30 days after transplantation.

The presence of at least 1 persistent mutation 30 days after ASCT was associated with a higher risk of disease progression compared with no mutation (53.1% vs 13.0%; conditioning regimen-adjusted hazard ratio [HR], 3.86; 95% CI, 1.96-7.62; P <.001). Persistent mutation was also associated with a reduced 1-year rate of progression-free survival (PFS) compared with no mutation (31.3% vs 59.3%; conditioning regimen-adjusted HR for progression or death, 2.22; 95% CI, 1.32-3.73; P =.005).

Additionally, the rate of PFS was lower in patients who underwent reduced-intensity conditioning and had at least 1 persistent mutation at 30-days post-ASCT compared with patients who underwent other conditioning regimens and had different mutation status (P ≤.001).

Multivariate analysis confirmed these results, showing that patients with a mutation at day 30 experienced a higher risk of disease progression (HR, 4.48; 95% CI, 2.21 to 9.08; P <.001) and a lower rate of 1-year PFS (HR for progression or death, 2.39; 95% CI, 1.40-4.09; P =.002) than patients with no mutation post-ASCT.

“Although this exploratory study has limitations, our results suggest that sequencing-based detection of tumor cells and measurable residual disease after allogeneic hematopoietic stem-cell transplantation has prognostic significance for patients with MDS,” concluded the authors.

Reference

1. Duncavage EJ, Jacoby MA, Chang GS, et al. Mutation clearance after transplantation for myelodysplastic syndrome. N Engl J Med. 2018;379(11):1028-1041.

Share this content:
You must be a registered member of Hematology Advisor to post a comment.

SIGN UP FOR FREE E-NEWSLETTERS