Cord Blood Transplantation versus Other Donor Sources in High-Risk Acute Myeloid Leukemia

Outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with high-risk acute myeloid leukemia (AML), including those with adverse disease biology or chemotherapy-refractory disease, remain suboptimal. Although an HLA-matched sibling donor (MSD) is preferred when available, other donor sources such as unrelated donors, haploidentical family donors (HID), and 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. By examining whether the strong GVL effect of CB is effective even in high-risk AML, we aim to inform future donor source selection. We retrospectively analyzed patients with high-risk AML who underwent first allogenic HSCT at our institution between 2008 and 2024. High-risk AML was defined as AML with adverse karyotype risk (according to ELN criteria), AML myelodysplasia-related (AML-MR), postcytotoxic therapy AML, or poor treatment response (primary induction failure or relapsed disease). Patients aged >65 years, with ECOG performance status (PS) 3 to 4, or favorable cytogenetics were excluded. The primary endpoint was progression-free survival (PFS), overall survival (OS), cumulative incidence of relapse, and nonrelapse mortality (NRM). To adjust for baseline differences, both multivariate analyses and propensity score matching were performed. 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%), postcytotoxic therapy AML in 45 (9.2%), and poor treatment response in 298 (61.0%). Age was higher in CB recipients (56 versus 48 years in median, P < .01) and fewer patients were in CR at HSCT (15.0% versus 35.1%, P < .01). Earlier transplantation year (<2016) was more common in other donors (62.8% versus 42.1%, P < .01). In multivariate analysis, CB was associated with better PFS (hazard ratio [HR] = .73, 95% confidence interval [CI]: .54 to .98, P = .04) and lower relapse (HR = .50, 95% CI: .33 to .75, P < .01). In the propensity score matched cohort (94 pairs), CB had a superior 5-year PFS (49.8% [95% CI: 40.2% to 61.7%] versus 35.4% [95% CI: 25.6% to 45.3%], overall P = .04), similar 5-year OS (56.2% [95% CI: 46.4% to 67.9%] versus 44.4% [95% CI: 35.0% to 56.4%], overall P = .16), lower 5-year cumulative incidence of relapse (24.5% [95% CI: 15.9% to 34.1%] versus 42.8% [95% CI: 32.4% to 52.8%], overall P < .01), and similar cumulative incidence of 5-year NRM (25.7% [95% CI: 17.1% to 35.2%] versus 21.8% [95% CI: 13.9% to 30.8%], overall P = .75). Among patients with high-risk AML, CB transplantation was associated with significantly lower relapse and superior PFS compared to other donor sources, in both multivariate and propensity score-matched analyses. These findings suggest that CB may offer outcomes comparable to, or potentially better than, other prioritized donor options for this poor-prognosis population, due to robust GVL effects.