Addition of High-Dose Cytarabine to Fludarabine, Busulfan, and Melphalan Conditioning for Cord Blood Transplantation in Adult Acute Myeloid Leukemia.

The clinical benefit of adding high-dose cytarabine (HDCA) to fludarabine (FLU), busulfan (BU), and melphalan (MEL)-based conditioning for cord blood transplantation (CBT) in acute myeloid leukemia (AML) remains unclear. We aimed to investigate the safety and efficacy of HDCA in this setting. We retrospectively analyzed 300 patients with adult AML who underwent first CBT between 2010 and 2019 using FLU (180 mg/m²), BU (12.8 mg/kg), and MEL (80 mg/m²). To ensure uniformity of conditioning intensity, patients receiving cytarabine at doses other than 8000 mg/m² were excluded. Among them, 116 patients received HDCA (total 8000 mg/m²) during conditioning (HDCA group), whereas 77 received FLU/BU/MEL alone (non-HDCA group). Overall survival, nonrelapse mortality (NRM), relapse incidence, and transplant-related complications were evaluated. The median follow-up period was 316 (range, 3-3508) days. Patients in the HDCA group were more likely to be aged ≤55 years, have a performance status (PS) of 0-1, and receive tacrolimus alone for graft-versus-host disease prophylaxis than patients in the non-HDCA group. The 1-year OS rate was significantly higher in the HDCA group than in the non-HDCA group (64% versus 46%, P = .019), whereas the 1-year NRM (27% versus 39%) and relapse incidence (12% versus 17%) rates did not significantly differ between the two groups. However, after adjustment for baseline imbalances using propensity score matching, no statistically significant differences in OS, NRM, or relapse were observed between the groups. Rates of neutrophil engraftment, infections, and graft-versus-host disease were comparable between groups. Multivariate analysis identified age ≥56 years and PS ≥2 as independent adverse prognostic factors for overall survival. Among patients aged ≤55 years, omission of HDCA was independently associated with a higher risk of relapse. HDCA intensification of FLU/BU/MEL conditioning appears feasible without increasing transplant-related toxicity. Although an improvement in overall survival was observed in unadjusted analyses, no significant benefit was confirmed after adjustment for baseline imbalances. The potential reduction in relapse among younger patients should be considered exploratory. Further prospective studies incorporating molecular risk stratification are warranted.