Background: Myelodysplastic syndromes (MDS) are malignant hematologic disorders characterized by ineffective hematopoiesis and an increased risk of progression to acute myeloid leukemia (AML). Higher-risk MDS patients typically have a survival of less than one year, and allogeneic hematopoietic cell transplantation (allo-HSCT) remains the only curative option (Bartenstein and Deeg, 2010). Pre-transplant cytoreductive therapy aims to reduce the disease burden, but its impact on post-transplant outcomes has been controversial (Niederwieser and Kröger, 2021; Kim et al., 2014; Wang et al., 2021; Schroeder et al., 2019). This retrospective study evaluates the effect of pre-transplant cytoreductive therapy on post-transplant outcomes in MDS with excess blasts (EB) patients.

Methods: We analyzed 313 patients who underwent allo-HCT for MDS with EB at the Asan Medical Center between December 1995 and December 2023. Patients were categorized based on whether they received pre-transplant cytoreductive therapy (cytoreductive group) or proceeded directly to transplantation (upfront HSCT group). Primary endpoints included overall survival (OS) and event-free survival (EFS); secondary endpoints were cumulative incidence of relapse (CIR) and non-relapse mortality (NRM).

Results: Among the entire cohort, 57 patients (18.2%) underwent upfront HSCT, while 256 patients (80.8%) received pre-transplant cytoreductive therapy. The cytoreductive therapy included hypomethylating agents (90.6%), conventional induction chemotherapy (10.2%), and low-dose cytarabine (3.5%). The median age was significantly younger in the upfront allo-HSCT group compared to the cytoreductive group (43 vs. 57 years, respectively). The median interval from diagnosis to allo-HSCT was 5.0 months; it was significantly delayed in the cytoreductive group compared to the upfront group (5.3 vs. 3.4 months). The proportion of patients classified as Very High Risk according to IPSS/IPSS-R at the time of MDS-EB diagnosis was higher in the upfront HCT group (64.9% vs. 52.3%). In the overall population, the 5-year OS did not differ significantly between patients who received pre-transplant cytoreductive therapy and those who did not (49.5% vs. 47.3%, p = 0.752). Similarly, there were no statistically significant differences in 5-year EFS (47.9% vs. 44.2%, p = 0.608), NRM (17.3% vs. 27.5%, p = 0.115), and CIR (p = 0.357). After adjusting for imbalances in baseline characteristics using propensity score matching, there were also no significant differences observed in OS, EFS, NRM, or CIR between the two groups.

In the cytoreductive groups, patients who achieved marrow CR or better responses following therapy showed significantly higher 5-year OS than those who failed to achieve responses (51.8% vs. 43.9%, p = 0.035), but the 5-year OS was comparable between patients in the upfront group and those in the cytoreductive group achieving responses (50.3% vs. 51.8%). Similar trends were observed in EFS and NRM. In multivariate analysis, a longer interval from diagnosis to allo-HSCT was independently associated with inferior OS and EFS. Additionally, haploidentical donor transplantation was associated with significantly shorter OS compared to matched unrelated or sibling donors (hazard ratio [HR] 1.86, p < 0.001). When comparing GVHD prophylaxis regimens, the use of post-transplant cyclophosphamide was associated with better OS than anti-thymocyte globulin. Age and IPSS/IPSS-R risk categories were also identified as independent prognostic factors for OS.

Conclusion: Pre-transplant cytoreductive therapy in MDS with EB did not improve post-transplant outcomes, and lack of response to cytoreductive therapy and delays in allo-HSCT adversely affected post-transplant outcomes. Donor type and GVHD prophylaxis also significantly impacts post-transplant outcomes. These findings suggest that pre-transplant therapy may help prevent disease progression, but it should be carefully considered and individualized. In particular, allo-HSCT should not be delayed solely due to pre-transplant cytoreductive therapy.

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2025
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