The impact of the use of hypomethylating agents prior to reduced intensity conditioning allogeneic bone marrow transplant among patients with MDS.

6557 Background: Allogeneic transplantation is the only potential cure for patients with myelodysplastic syndrome (MDS). It is unclear whether cytoreduction with hypomethylating agents (HMAs) prior to reduced intensity conditioning (RIC) transplantation in patients with 5–10% bone marrow blasts impact transplant outcomes. Methods: We utilized the publicly available CIBMTR dataset from the publication “Alternative Donor Transplantation for Myelodysplastic Syndrome: Haploidentical Relative and Matched Unrelated Donor” to evaluate the differences in relapse-free survival (RFS), transplant-related mortality (TRM), and overall survival (OS) between recipients and non-recipients of pretransplant HMAs among MDS patients undergoing RIC Allo-SCT. The two groups were matched on confounding variables, including donor type, blast percentage at diagnosis and at the time of transplant, age, sex, race, IPSS-R score, CMV donor status, conditioning regimen, time to transplant, and year of diagnosis. Matching was performed using the inverse probability of treatment weights (IPTW) method. Weighted Kaplan-Meier curves were used to evaluate OS, RFS, and TRM between the two groups. Additionally, a doubly robust Cox regression model was constructed to estimate hazard ratios (HR) for the effect of pretransplant HMA use on OS and RFS. Results: A total of 603 patients were included in our analysis. The median age was 67.1 years (IQR 63.1–70.5), and the median follow-up was 21.8 months (0.95 CI 13.1–NR). In the weighted data. The 0.75 quantile for RFS was 7.57 months (0.95 CI 6-NR months) for the non-HMA group versus 5.79 months (0.95 CI 4.14–6 months) for the HMA group (P = 0.027). Similarly, the 0.75 quantile for OS was 9.54 months (0.95 CI 7.96–NR) for the non-HMA group versus 5.79 months (0.95 CI 4.38–7.43 months) for the HMA group (P = 0.005). There was no significant difference in the incidence of acute or chronic GVHD or TRM. In doubly robust Cox regression model. Pretransplant HMA was associated with worse RFS and OS with a HR of 0.66 (0.95 CI 0.44-0.97, P value =0.035) and HR of 0.60 (0.95 CI 0.42-0.90, P value< 0.01) respectively. Conclusions: Pretransplant use of HMA in MDS patients with less than 10% bone marrow blasts is associated with worse RFS and OS following allogeneic SCT with RIC. Notably, this detrimental impact is most pronounced in patients with less than 5% blasts, raising critical questions about the role of pretransplant HMA in this low-risk subgroup and emphasizing the need for refined treatment strategies. Doubly robust (weighted) Cox-regression model on RFS. Variable Estimate Lower .95 CI Upper .95 CI P-Value No-Hypomethylating agents before Transplant (Reference=HMA pretransplant) 0.66 0.44 0.97 0.035 Sex (Reference=Male) 1.27 0.89 1.80 0.186 MUD VS Haploidentical 0.92 0.42 2.02 0.84 Poor cytogenetics (Reference=very good and good) 3.9 2.66 5.82 <0.01