Upfront Allogeneic Hematopoietic Stem Cell Transplantation Can Provide Survival Benefit Versus Hypomethylating Agent in Myelodysplastic Syndrome with Increased Blasts I (MDS-IB I)

Topic: 22. Stem cell transplantation - Clinical Background: Myelodysplastic syndrome (MDS) is a group of clonal disorders of hematopoietic stem cell. Survival would be significantly shortened if excessive blasts appear in marrow or the periphery. As disease progression accelerating, about 25% of MDS-IB1 and 33% of MDS-IB2 patients were reported to finally transformed into leukemia. Currently, allogeneic stem-cell transplantation (Allo-HSCT) still remains the only curable treatment accompanied with risk of therapy related mortality and decline of life quality. Decitabine (DAC), an of DNA methylation, was also reported to exhibit benefit in treatment of MDS. Thus, comparative studies with Allo-HSCT are needed. Aims: To retrospectively compare response of upfront allogeneic HSCT with hypomethylating agent (DAC in 87.5% of the group) therapy according to stem-cell donor availability in patients with MDS-IB1. Methods: We retrospectively reviewed 103 patients with primary MDS patients who were evaluated and received treatment in our center between August 2011 and August 2020. Overall survival (OS), event-free survival (EFS), non-relapse mortality (NRM) and cumulative rate of relapse or progression (CIR) at 1 year was calculated according to treatment arm. Cox regression analyses with allo-HSCT as time-dependent covariate (Mantel-Byar approach) were performed. Results: One-hundred and three patients with a median age of 49 years were included. Allo-HSCT was performed in 61.2% (n=63) and the rest 38.8% (n=40) received continuous HMA. The median follow-up time for surviving patients was 30.4 months (range: 3.2-122.1 months). In the entire cohort, non-relapse mortality rate at 1 year was significantly higher in the allo-HSCT group compared with HMA group (14.3% vs. 2.5%, P=0.008), and the cumulative incidence of relapse and progression at 1 year was significantly lower (1.6% vs. 45.5%, P<0.001). After matching with propensity-score, the overall survival rate at 3 years was 77.8% in the allo-HSCT group compared with 43.5% in the HMA group with a significant difference by Cox-regression considered allo-HSCT as time-dependent covariate (P=0.045), and event-free survival rate at 3 years was higher in allo-HSCT patients (73.4%) compared with HMA group (20.6%; P=0.001). Summary/Conclusion: In MDS-IB1 patients, allogeneic HSCT resulted in significantly prolonged overall survival and event-free survival compared with continuous HMA therapy. MDS-IB1 patients may be benefit from an earlier upfront allo-HSCT plan.Figure legend: (A-B) Simon-Makuch curve for (A) OS and (B) EFS in the entire cohort after HMA or HSCT; (C-D) Simon-Makuch curve for (C) OS and (D) EFS in matched cohort after HMA or HSCT. Keywords: Allogeneic hematopoietic stem cell transplant, Myelodysplastic syndrome