Upfront Allogeneic Hematopoietic Stem Cell Transplantation Can Provide Survival Benefit Versus Hypomethylating Agent in Myelodysplastic Syndrome with Increased Blasts I (MDS-IB I)
Authors: Ma Runzhi , Zhen Sisi , Liu Li , Wang Jieru , Jiang Erlie , Feng Sizhou 
Published: December 2023

Introduction
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.
Objective
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
According to the International Prognostic Scoring System (IPSS), 55 patients (55%) were stratified into lower-risk and 46 patients (45%) were stratified into higher-risk (IPSS intermediate 2 or high risk). Allogeneic HSCT was performed in 61.2% (n=63) and the rest 38.8% (n=40) received continuous HMA. In the no-donor group, 28 patients (70%) experienced disease progression or relapse after remission and leukemia transformation was noted in 14 patients (35%). The median follow-up time for surviving patients was 30.4months (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&lt;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). The advantage of allo-HSCT was seen in those who aged &gt; 50 years, male, those with ineffective erythropoiesis and without iron overload.
Conclusion
We concluded that patients with MDS-EB1 significantly benefited from receiving allo-HSCT with prolonged OS and EFS compared with continuous HMA (DAC) therapy. The advantage of allo-HSCT has been seen in subgroups of patients who age &gt;50 years, male, those with ineffective erythropoiesis and without iron overload. Even earlier myeloablative allo-HSCT prevents further progression of MDS-EB1 at risk of higher non-relapse mortality, upfront allo-HSCT should be considered in a donor available scenario.