Can Cord Blood Unit Selection Improve Outcomes After Single-Unit Unrelated Cord Blood Transplantation for Non-Remission Acute Myeloid Leukemia?
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BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is the only established curative therapy for acute myeloid leukemia (AML) refractory to chemotherapy. Unrelated umbilical cord blood transplantation (CBT) provides a valuable alternative donor source for these patients, but whether cord blood unit selection can improve outcomes after single-unit CBT in non-remission AML remains uncertain. METHODS: We retrospectively analyzed 3256 adult patients with non-remission AML who underwent single-unit CBT as their first allogeneic HCT between 1998 and 2023 in Japan, using data from the nationwide Japanese Data Center for Hematopoietic Cell Transplantation. Cord blood-related factors, including cryopreserved total nucleated cell (TNC), CD34⁺ cell, and colony-forming unit-granulocyte/macrophage (CFU-GM) doses, HLA mismatches, and donor-recipient sex and ABO compatibilities, were evaluated for their associations with overall survival (OS), leukemia-free survival (LFS), relapse, non-relapse mortality (NRM), hematopoietic recovery, and graft-versus-host disease (GVHD). RESULTS: In multivariable analyses, a CD34⁺ cell dose ≥0.608 × 10⁵/kg was associated with decreased overall mortality compared with <0.608 × 10⁵/kg. Compared with sex-matched transplantation, female-to-male donor-recipient sex incompatibility was also associated with higher overall mortality (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.00 to 1.23), whereas male-to-female sex incompatibility was associated with reduced mortality (HR, 0.87; 95% CI, 0.78 to 0.98). Regarding HLA serologic compatibility, compared with 2 mismatches, 0 mismatches (HLA match) were associated with a higher risk of relapse (HR, 1.37; 95% CI, 1.17 to 1.61) but a lower risk of NRM (HR, 0.69; 95% CI, 0.53 to 0.89). Regarding HLA allele-level compatibility, compared with 3 mismatches, 0 to 1 mismatches were associated with a higher risk of relapse (HR, 1.26; 95% CI, 1.06 to 1.50), whereas ≥5 mismatches were associated with increased NRM (HR, 1.32; 95% CI, 1.01 to 1.73). Higher CD34⁺ cell and CFU-GM doses were associated with faster hematopoietic recovery, but a higher CFU-GM dose was associated with an increased risk of chronic GVHD. CONCLUSIONS: Among adults with non-remission AML undergoing single-unit CBT, CD34⁺ cell dose, CFU-GM count, and donor-recipient sex compatibility were independent predictors of survival and engraftment. Furthermore, the degree of HLA mismatch exhibited a complex relationship with relapse and NRM, highlighting the need for balanced graft selection strategies that optimize both engraftment and disease control in CBT for non-remission AML.