Abstract
Recent advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) strategies and supportive care may have increased access to allo-HSCT and improved post-transplant outcomes in myeloid neoplasms. To clarify survival trends after allo-HSCT by disease type, we conducted a nation-wide retrospective study of unselected patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN).
This study included patients who (i) were diagnosed with de novo MDS, de novo MDS/MPN, or therapy-related MDS and MDS/MPN (t-MN); (ii) were 16 years or older; and (iii) underwent their first allo-HSCT between 1998 and 2022. Disease status in de novo MDS was defined as advanced disease if refractory anemia with excess blasts (RAEB) or RAEB in transformation had been present at any point from diagnosis to allo-HSCT; all others were classified as early disease. Transplantation periods were categorized as 1998-2012 (early period), 2013-2017 (middle period), and 2018-2022 (late period). Risk factors were analyzed using Cox proportional hazards models for overall survival (OS) and Fine and Gray's proportional hazards models for cumulative incidence of relapse (CIR) and non-relapse mortality (NRM).
Among 7175 patients, diagnoses were as follows: early MDS (n=1675), advanced MDS (n=4254), chronic myelomonocytic leukemia (CMML; n=444), atypical chronic myeloid leukemia (aCML; n=89), MDS/MPN-unclassifiable (MDS/MPN-U; n=166), and t-MN (n=548). Across all disease entities, the annual numbers of allo-HSCT increased over time, with a notable increase in patients aged 60 years or older. The use of unrelated cord blood grafts increased over time, and the use of grafts from HLA-haploidentical related donors markedly increased in the late period.
In early MDS patients, multivariate analysis revealed that OS significantly improved in the middle period (hazard ratio [HR] 0.79 [95% confidence interval, 0.65-0.97]; P=0.026) and further in the late period (HR 0.54 [0.42-0.70]; P<0.001) compared to the early period. NRM also improved in the middle (HR 0.75 [0.59-0.95]; P=0.018) and late periods (HR 0.50 [0.37-0.67]; P<0.001). No significant improvement in CIR was seen across three periods.
In advanced MDS patients, OS significantly improved in the middle (HR 0.80 [0.71-0.90]; P<0.001) and late periods (HR 0.74 [0.65-0.85]; P<0.001) compared to the early period, and NRM also improved in the middle (HR 0.76 [0.64-0.90]; P=0.001) and late periods (HR 0.65 [0.55-0.78]; P<0.001). No statistically significant difference in OS and NRM was seen between the middle and late periods. No significant trend toward improvement in CIR was observed across three periods.
We next evaluated outcomes in patients with de novo MDS/MPN. In CMML patients, multivariate analysis revealed that OS was better in the middle (HR 0.45 [0.32-0.64]; P<0.001) and late period (HR 0.53 [0.37-0.74]; P<0.001), and NRM was also better in the middle (HR 0.49 [0.27-0.89]; P=0.020) and late periods (HR 0.42 [0.22-0.81]; P=0.009). No significant difference in OS was seen between the middle and late periods. CIR did not improve across three periods.
In aCML patients, OS was significantly better in the middle (HR 0.32 [0.13-0.80]; P=0.016) and late periods (HR 0.26 [0.10-0.68]; P=0.006) than the early period, and NRM was significantly better in the late period (HR 0.30 [0.09-0.98]; P=0.047). No significant improvement in CIR was observed across the three periods.
In MDS/MPN-U patients, no statistically significant improvement in OS, NRM, and CIR was seen over the three periods.
In t-MN patients, multivariate analysis showed that NRM significantly improved in the late period (HR 0.64 [0.42-0.96]; P=0.031) compared to the early period, but there was no significant trend toward improvement in OS and CIR over time.
The development of transplant modalities has resulted in an increased number of allo-HSCT for MDS and MDS/MPN patients. The survival in early MDS patients has shown sustained improvement over time. In advanced MDS, CMML, and aCML patients, the survival markedly improved after the middle period, but little further improvement has been observed after the late period. In addition, the survival in MDS/MPN-U and t-MN patients showed a lack of significant overall improvement. These results indicate a clear need to develop more effective therapeutic strategies in advanced MDS, MDS/MPN, and t-MN patients.
