Cord blood transplantation in FLT3-mutated versus FLT3-wild-type AML

Patients with acute myeloid leukaemia (AML) undergoing first-time umbilical cord blood transplantation (UCBT) demonstrated more favourable outcomes when harbouring FLT3 mutations compared with FLT3–wild-type AML, including longer progression-free survival (PFS) and lower relapse rates. In addition, post-transplant FLT3 inhibitor (FLT3i) maintenance therapy showed potential clinical benefit.

Allogeneic haematopoietic stem cell transplantation (allo-HCT) is a commonly used therapeutic strategy in FLT3-mutated AML and may contribute to prolonged overall survival (OS). When a suitable donor is unavailable, UCBT represents a potential alternative, alongside haploidentical T-cell–depleted peripheral blood stem cell transplantation. UCBT is thought to provide a stronger graft-versus-leukaemia (GvL) effect compared with other graft sources, although supporting data remain limited. In a retrospective study (jRCT1031230158), a Japanese research group compared the outcomes after UCBT in patients with FLT3-mutated versus FLT3-wild-type AML. Interim 1-year results from this single-centre analysis were presented by Dr Aya Nishida (Toranomon Hospital, Japan) [1].

Among 177 eligible patients who underwent their first UCBT at Toranomon Hospital between January 2019 and December 2023, 36 patients had FLT3-mutated AML, and 31 had FLT3-wild-type AML. All patients in the FLT3-mutated cohort harboured FLT3 internal tandem duplication (ITD) mutations. The median age was 56.4 years in both cohorts, and all but 3 participants had de novo AML.

The results demonstrated a trend toward improved 1-year PFS in the FLT3-mutated cohort compared with the FLT3-wild-type cohort: 70.6% versus 51.6% (P=0.14). A similar trend was observed for OS: 70.6% versus 54.5% (P=0.39). In univariate analysis, the relapse rate was significantly lower in patients with FLT3-mutated disease than in those with FLT3-wild-type disease: 7.0% versus 27.0% (P=0.02). By contrast, non-relapse mortality (NRM) did not differ significantly between groups: 21.0% versus 34.5% (P=0.55).

In multivariate analysis, age ≥60 years and higher transplant-related comorbidity burden (HCT-CI ≥2) were associated with inferior OS and PFS. No factors were significantly associated with relapse risk. Within the FLT3-mutated cohort, post-transplant FLT3i maintenance therapy with gilteritinib showed potential clinical benefit, although selection bias could not be excluded. Among the 19 patients who received gilteritinib maintenance, both PFS and OS were 78.6%, while the relapse rate was 5.3%, and NRM was 16.1%.

Nishida A, et al. Comparison of umbilical cord blood transplantation outcomes between FLT3-mutated and -wild-type AML in a matched-pair cohort. P119, EBMT congress 2026, 22-25 March, Madrid, Spain.