Effect of peri-transplant measurable residual disease clearance in patients with myelodysplastic neoplasm; a referral center experience: Effect of peri-HSCT MRD Clearance in MDS.

Abstract

Peri-allogeneic stem cell transplant (peri-HSCT) measurable residual disease (MRD) is increasingly recognized as a prognostic marker. However, the MRD status in myelodysplastic neoplasm (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), are less well-established compared to B-Acute Lymphoblastic Leukemia. We reviewed the charts of adults who underwent HSCT for MDS or MDS/MPN between 2012-2023 and evaluated the effect of pre-HSCT MRD status on relapse-free and overall survival (RFS and OS). A conditional analysis of outcomes based on day+90 post-HSCT MRD status was also performed. There were 38 and 55 patients in MRD- and MRD+ cohorts respectively. Baseline patient characteristics, including age, Revised and Molecular International Prognostic Scores (IPSS-R & IPSS-M), and HSCT-related factors were similar between MRD+ and MRD- cohort. 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). Among 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 they became MRD- by day +90 post-HSCT. Pre- and peri-HSCT MRD testing could offer valuable prognostic information in patients with MDS and MDS/MPN. Teaser Abstract: Not overall survival (OS) but relapse free survival (RFS) can be affected by pre-allogeneic stem cell transplant (pre-HSCT) measurable residual disease (MRD) clearance in patients with myelodysplastic neoplasm (MDS) but more importantly, there is no significant difference in OS and RFS in patients who achieve MRD negative complete remission by day+90 post-HSCT. Graft-versus-tumor effect may exert its effect later in the HSCT course, and clearance of MRD pre-HSCT alone may not reliably predict HSCT outcomes. Post-HSCT MRD surveillance should be performed routinely in MDS patients.