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Hypomethylating treatment (HMT) has been suggested as a feasible bridge to hematopoietic stem cell transplantation (HSCT), but controversies exist around influences of HMT response on transplant outcomes. To assess the safety and influences of pre-transplant HMT focusing on debulking effects and transplant outcomes, we retrospectively analyzed consecutive HSCT-eligible patients who received HMT for higher-risk MDS with excess blasts. Of all 98 patients, 11 patients failed to proceed to HSCT and HMT-related mortality occurred in 8 patients. When excluding 9 patients who refused HSCT, 87% of scheduled HSCT (77 of 89) was performed after a median of 3 cycles (range, 1-8) of HMT. The 4-year overall survival after HMT (n = 98) and HSCT (n = 77) was 44.0% and 53.6%, respectively. Transplant outcomes were significantly different by the final response at HSCT; marrow response group (complete remission, marrow complete remission with or without hematologic improvement) showed significantly better 4-year disease-free survival compared to no marrow response group (n = 36, 87.3% vs. n = 41, 10.7%, P &lt; 0.001). This difference between the groups was also evident in overall survival (90.9% vs. 8.6%, P &lt; 0.001) and cumulative incidences of relapse (6.5% vs. 45.4%, P &lt; 0.001) and treatment-related mortality (6.2% vs. 43.9%, P &lt; 0.001). These observations indicate that pre-transplant HMT is a feasible bridging treatment in patients with excess blasts regarding high success rate of proceeding to transplantation and good survival rate. Marrow response at HSCT regardless of concomitant hematological improvement is an independent predictor of better survival, suggesting that immediate HSCT rather than continuing HMT should be performed once marrow response is achieved.

Better transplant outcome with pre-transplant marrow response after hypomethylating treatment in higher-risk MDS with excess blasts