Allogeneic hematopoietic cell transplantation (HSCT) remains the only curative treatment in patients with myelodysplastic syndrome (MDS). However, due to the transplant-related toxicity, the benefit of HSCT over other non-cellular therapy is restricted to patients at high risk of disease progression. We analyzed outcomes of MDS patients undergoing HSCT in the last 2 decades to determine whether outcomes have improved over time and identify which variables influence such outcomes.

MDS patients recorded in the EBMT registry, transplanted from all allogeneic donors (unrelated cord blood donor (UCB), or an HLA-matched or mismatched donor) between 2000 and 2022, were included but those transformed to Acute Myeloid Leukemia before transplant were excluded. Overall survival (OS), relapse-free survival (RFS), relapse, non-relapse mortality (NRM) were analyzed in non-overlapping 5-year cohorts defined by year of HSCT (2000-2004, 2005-2009, 2010-2013, 2014-2017 and 2018-2022). The Kaplan-Meier estimator was used for OS, and RFS and the log-rank test was used to compare differences between groups. The crude cumulative incidence estimator and Gray's test were used for competing events. Multivariable analyses (MVA) were performed using Cox proportional hazards models, including interaction terms between baseline variables and calendar period of HSCT.

Overall, 18,710 patients were included in the analysis. Median age at transplant increased from 49.7 years in the earliest period (2000-2004) to 61.5 years in the most recent analyzed period (2018-2022). The majority of patients were transplanted for MDS with excess blasts (MDS-EB) (62%) with a stable proportion over time. 4-year OS, RFS, NRM improved over time and were 44% (95% CI: 42-47), 39% (95% CI: 36-41), and 35% (95% CI: 32-37) during 2000-2004 and 53% (95% CI: 51-55), 47% (95% CI: 45-48) and 24% (95% CI: 23-25) in the most recent period, respectively. The 4-year cumulative incidence of relapse did not significantly change over time being 26% across all groups. In the MVA for OS, compared to the use of an HLA matched donor (MRD), the hazard ratios (HR) were 1.42 (95% CI's in all parentheses 1.30-1.54) for a mismatched related donor (MMRD), 1.05 (1.00-1.11) for matched unrelated donor (MUD), 1.30 (1.21-1.39) for mismatched unrelated donor (MMUD), and 1.69 (1.46-1.95) for UCB. Other variables influencing OS were older age at HSCT [HR: 1.18 per 10 years older (1.15-1.20)], male recipient sex [HR: 1.10 (1.04-1.15)], lower Karnofsky score [80 versus (vs) ≥90:1.32 (1.26-1.39); <80, HR: 1.75 (1.51-2.03)], higher comorbidity score [intermediate vs low: 1.10 (1.03-1.18), high, HR: 1.26 (1.19-1.35)], positive CMV serology in the patient [HR: 1.19 (1.13-1.25)], male recipient / female donor, HR vs other donor- recipient sex combinations: 1.09 (1.02-1.14), HSCT whilst not in CR vs CR [HR: 1.15 (1.09-1.22)], and poorer cytogenetic risk [intermediate vs good or very good risk IPSS-R, HR: 1.17 (1.08-1.26), poor, HR: 1.36 (1.24-1.49), very poor, HR: 1.91 (1.78-2.05)]. These factors were similarly associated with RFS. All variables that impacted OS and -RFS also impacted NRM. While a reduced intensity regimen decreased the risk of NRM [HR compared to myeloablative: 0.84 (0.79-0.90), this was counterbalanced with an increased risk of relapse (HR 1.22 (1.13-1.30)]. Despite the inclusion of these factors in the survival models, a significant association between the latest HSCT time group and better OS, RFS, NRM and relapse was noticed. Moreover, the association of some of these variables and outcome after HSCT improved over time. For instance, the risk of poorer OS and RFS for MMRD, MMUD and UCB compared to MRD improved over time albeit remaining significant (RFS HR during 2000-2004 for MMRD was 1.61 (1.14-2.27), MMUD was 1.47 (1.20-1.81), UCB was 2.89 (1.66-5.03) and had changed to 1.19 (1.05-1.34), 1.16 (1.01-1.32) and 1.53 (1.07-2.17), respectively in the 2018-2022 period).

Altogether, our data over two decades show that despite increasing recipient age, the OS, RFS and NRM after MDS HSCT have progressively improved. Risk factors associated with outcome are also evolving, possibly due to progress in averting complications and transplant platforms.

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2025
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