Predicting Post-Transplant Disease Progression in Myelodysplastic Syndrome

Mutational analysis, combined with flow cytometry (FCM), to detect minimal residual disease (MRD) may aid in predicting disease progression following myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome (MDS). This is according to the results of a new study published in Frontiers in Oncology.

The study was a retrospective analysis of patients seen at the First Affiliated Hospital of Soochow University in Suzhou, China, who had MDS treated with allo-HSCT after myeloablative conditioning. The researchers performed mutational and FCM-based assessments of bone marrow samples at 30 days following allo-HSCT to evaluate MRD status. Mutational analyses utilized next-generation sequencing to examine a panel of 51 genes frequently associated with hematologic malignancies.

Sequencing results for MRD were categorized according to positivity (MUT^pos) or negativity (MUT^neg) for mutations present at day 30 after transplantation. FCM-based assessments of MRD were rated as FCM^high if ≥0.1% or FCM^low if <0.1%. The goal of the study was to explore any correlations between mutational or FCM-based MRD levels and clinical outcomes.

A total of 181 patients with MDS were evaluated in this study. Of these, 115 patients had 1 or more mutations at the time of diagnosis or prior to allo-HSCT and were included in further analyses. From this group, 70.4% of patients had FCM^low/MUT^neg status, 13.9% displayed FCM^high/MUT^neg status, 11.3% had FCM^low/MUT^pos status, and 4.3% of patients had FCM^high/MUT^pos status.

The FCM^high/MUT^pos group had a 2-year progression-free survival (PFS) rate of 20%, compared with a rate of 79% for the FCM^low/MUT^neg group (unadjusted hazard ratio [HR], 7.801; P <.001). In univariate analysis, poor PFS was also associated with several other factors. These included a revised International Prognostic Scoring System (IPSS-R) score of ≥4 at allo-HSCT (HR, 5.061; P =.007), poor or very poor IPSS-R cytogenetic risk at diagnosis (HR, 4.906; P <.001), and presence of TP53 mutations (HR, 3.946; P =.011), with presence of DNMT3A mutations trending toward poor PFS (HR, 2.291; P =.052). All of these factors were included in multivariate analysis.

Multivariate analysis revealed a few factors to be independent risk factors for progressive disease. These included FCM^high/MUT^pos status at day 30 (HR, 5.198; P =.013), IPSS-R score ≥4 at allo-HSCT (HR, 4.488; P =.015), poor or very poor IPSS-R cytogenetic risk at diagnosis (HR, 3.061; P =.042), and presence of DNMT3A mutations (HR, 2.385; P =.049).

“In summary, our data strongly indicated that the monitoring of MRD by both FCM and gene mutation clearance at day 30 could help in the prediction of relapse of MDS patients after myeloablative transplantation,” the researchers concluded in their report. They recommended further study based on a clinical trial to evaluate the utility of this approach in clinical practice.

Reference

Hou C, Zhou L, Yang M, et al. The prognostic value of early detection of minimal residual disease as defined by flow cytometry and gene mutation clearance for myelodysplastic syndrome patients after myeloablative allogeneic hematopoietic stem-cell transplantation. Front Oncol. 2021;11:700234. doi:10.3389/fonc.2021.700234