Background: Outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk acute myeloid leukemia (AML), including those with adverse disease biology or chemotherapy-refractory disease, remain suboptimal. While HLA-matched sibling donor (MSD) is preferred when available, other donor sources such as unrelated donors, haploidentical family donors (HID), and umbilical cord blood (CB) are viable alternatives. CB has been associated with potent graft-versus-leukemia (GVL) effects in several studies and may therefore represent a suitable donor option for high-risk populations. However, data directly comparing outcomes of CB with other donor sources in high-risk AML remain limited.

Methods: We retrospectively analyzed patients with high-risk AML who underwent first allo-HSCT at our institution between 2008 and 2024. High-risk AML was defined as AML with adverse cytogenetic risk (according to ELN criteria), AML myelodysplasia-related (AML-MR), post cytotoxic therapy AML, or poor treatment response (primary induction failure or relapsed disease). Patients aged >65 years, with ECOG performance status (PS) 3–4, or favorable cytogenetics were excluded. The primary endpoint was leukemia-free survival (LFS); secondary endpoints included overall survival (OS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and neutrophil engraftment. To adjust for baseline differences, both multivariate analyses and propensity score matching were performed, adjusting for age, transplantation year, conditioning intensity, remission status, PS, and cytogenetic risk. Propensity score matching was conducted using 1:1 optimal matching without replacement, based on a logistic regression model. The probability of LFS and OS were estimated using the Kaplan–Meier method and compared using the log-rank test. CIR, NRM, and neutrophil engraftment were analyzed using cumulative incidence functions accounting for competing risks. Multivariate analyses were performed using Cox proportional hazards or Fine–Gray models.

Results: A total of 488 patients were included: 394 (80.7%) received CB and 94 (19.3%) received other donor sources, including 46 MSD, 6 HID, and 42 unrelated bone marrow or peripheral blood donors (25 matched, 17 mismatched). Adverse cytogenetic risk was present in 189 (38.7%), AML-MR in 233 (47.7%), post cytotoxic therapy AML in 45 (9.2%), and poor treatment response in 298 (61.0%). Age was higher in CB recipients (56 vs 48 years in median, p<0.01) and more patients were not in CR at HSCT (85.0% vs. 64.9%, p<0.01). Adverse cytogenetics tended to be more frequent in CB (40.9% vs. 29.8%, p=0.06). Earlier transplantation year (<2016) was more common in other donors (62.8% vs. 42.1%, p<0.01). Median follow-up among survivors was 78.8 months. In univariate analysis, 5-year LFS was 35.0% for CB and 35.4% for others (p=0.90); OS was 38.7% vs. 44.4% (p=0.10). CIR at 5 years was lower in CB (27.6% vs. 42.8%, p<0.01), and NRM was higher (37.4% vs. 21.8%, p=0.01). Neutrophil engraftment rate was lower in CB (89.3% vs. 94.7%, p<0.01). In multivariate analysis, CB was associated with better LFS (HR=0.73, 95% CI: 0.54–0.98, p=0.04) and lower relapse (HR=0.50, 95% CI: 0.33–0.76, p<0.01). Factors associated with worse LFS/OS included age >50, non-CR status, adverse cytogenetics, and PS 2. In the propensity score matched cohort (94 pairs), all covariates about baseline characteristics were well balanced (standardized mean differences <0.15). In the matched cohort analysis, CB demonstrated superior 5-year LFS of 49.6% (95% CI: 39.8–61.9%) compared to 35.4% (95% CI: 26.7–46.9%) with others (p = 0.03). OS was similar between the two groups: 55.6% (95% CI: 45.9–67.5%) for CB and 44.4% (95% CI: 35.0–56.4%) for others (p = 0.30).Five-year CIR was significantly lower in CB at 21.7% (95% CI: 13.4–31.3%) vs 42.8% (95% CI: 32.4–52.8%) in others (p < 0.01). NRM was comparable: 28.6% (95% CI: 19.4–38.5%) for CB vs 21.8% (95% CI: 13.9–30.8%) for others (p = 0.46).Conclusions: Among patients with high-risk AML undergoing allo-HSCT, CB transplantation was associated with significantly lower relapse and superior LFS compared to other donor sources, in both multivariate and propensity score-matched analyses. These findings support CB as a favorable donor option for this poor-prognosis population, potentially due to robust GVL effects, even when other prioritized donors are available.

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2025
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