Background: FLT3-mutated acute myeloid leukemia (AML) has long been associated with poor prognosis. The introduction of FLT3 inhibitors has improved outcomes, and in ELN 2022, FLT3-mutated AML is now classified as intermediate risk. While allogeneic hematopoietic stem cell transplantation (allo-HSCT) is commonly performed, data on umbilical cord blood transplantation (UCBT) for FLT3-mutated AML remain limited. UCBT is thought to provide a stronger graft-versus-leukemia (GVL) effect than other graft sources. We aimed to compare outcomes of UCBT between FLT3-mutated and wild-type AML and to identify prognostic factors.

Methods: We retrospectively analyzed adult AML patients who underwent first UCBT at Toranomon Hospital between January 2019 and December 2023. Patients without FLT3 mutation testing, with active infections, or with ECOG PS > 2 at transplantation were excluded. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints included 1- and 5-year relapse rates, non-relapse mortality (NRM), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method, with log-rank tests for group comparisons. Cox regression and Fine–Gray models were applied for multivariate analyses, accounting for competing risks. This report summarizes interim results at 1 year.

Results: Among 327 eligible patients, 177 were included in the analysis. The median age was 54 years (range, 24–77), and 103 patients were male (58.2%). According to the 2022 ELN risk classification at diagnosis, 8 patients were favorable, 122 intermediate, and 47 adverse. At the time of transplantation, 129 patients (72.9%) were not in remission. The median HCTCI score was 1 (range, 0–7). Myeloablative conditioning (MAC) was used in 132 patients (74.6%), and GVHD prophylaxis with tacrolimus plus MMF was used in 173 patients (97.7%). The median follow-up period for survivors was 608 days. The 1-year PFS and OS were 58% and 60.8%, respectively, with a relapse rate of 17.6% and NRM of 24.4%. The cumulative incidence of grade II–IV acute GVHD by day 100 was 69.5%, and moderate-to-severe chronic GVHD at 1 year was 2.8%.

FLT3 mutations were present in 36 patients (35 ITD, 1 TKD). FLT3-mutated AML showed significantly better 1-year PFS (74.7% vs. 53.7%) and OS (74.7% vs. 56.5%) compared with wild-type (P < 0.05), along with a trend toward a lower relapse rate (5.7% vs. 20.6%, P = 0.08), while NRM did not differ significantly (19.6% vs. 25.6%, P = 0.38). In multivariate analysis, disease status at transplant and ELN 2022 risk classification were independent prognostic factors for PFS.

Post-transplant maintenance with gilteritinib was administered in 22 patients and was associated with a trend toward improved outcomes, including a higher 1-year PFS (81.6% vs. 64.3%) and a lower relapse rate (4.5% vs. 14.3%, P < 0.05), although potential selection bias could not be excluded.Conclusions: In this cohort of first UCBT, FLT3-mutated AML demonstrated superior PFS and OS with a reduced relapse rate. Post-transplant FLT3 inhibitor maintenance therapy showed a potential benefit. Larger studies are warranted to validate these findings.

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2025
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