Can Cord Blood Unit Selection Improve Outcomes After Single-Unit Unrelated Cord Blood Transplantation for...

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.

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).

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.

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.