Effect of Pre- and Peri-Transplant Measurable Residual Disease Clearance in Patients with Myelodysplastic Neoplasm; A Referral Center Experience

Introduction

Measurable residual disease (MRD) has emerged as a potential prognostic marker for allogeneic stem cell transplant (HSCT) outcomes in various hematologic malignancies. However, the MRD status in myelodysplastic neoplasm (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), can be difficult to interpret due to heterogenous disease biology and unique limitations in each MRD measuring techniques. In comparison to B-cell acute lymphoblastic leukemia whose clearance of pre-HSCT MRD is considered essential, the data in MDS or MDS/MPN is less clear. As post-HSCT disease surveillance becomes more standardized, we also evaluated the effect of peri-HSCT MRD status on relapse-free and overall survival (RFS and OS) outcomes.

Methods

We reviewed records of adult patients who underwent HSCT for MDS or MDS/MPN at our institution between 2012-2023 and report the outcomes of patients between those who had undetectable MRD (MRD-) vs detectable MRD (MRD+) pre-HSCT and conducted a conditional analysis of outcomes based on MRD status at day+90 post-HSCT.

Results

We identified 38 and 55 patients in MRD- and MRD+ cohorts respectively. Baseline patient characteristics were similar between the cohorts, including age, Revised and Molecular International Prognostic Scores (IPSS-R & IPSS-M), and HSCT-related factors. The MRD+ cohort had inferior RFS (HR: 1.84, 95% CI: 1.09-3.12, p=0.02) but a statistically significant difference in OS was not evidenced (HR: 1.52, 95% CI: 0.88-2.61, p=0.14). After adjusting for % blasts at diagnosis, and conditioning intensity, MRD+ patients were found to be at 1.92 times increased risk of relapse or death (95% CI: 1.12-3.28, p=0.02). Additionally, increasing IPSS-M score was associated with poorer RFS (HR: 1.27, 95% CI: 1.01-1.59, p=0.04) and OS (HR: 1.52, 95% CI: 1.20-1.91, p<0.01). On a conditional analysis of patients who were alive and in remission until day +90 post-HSCT, the pre-HSCT MRD status did not confer a statistically significant difference in RFS and OS if patients were able to achieve an MRD- status by day +90 post-HSCT.

Conclusion:

Pre- and peri-HSCT MRD testing may offer valuable survival prognostic information in patients with MDS and MDS/MPN and should be considered part of routine disease surveillance.

No relevant conflicts of interest to declare.