Impact of Graft Cell Dose on Transplant Outcomes following Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation: Higher CD34⁺ Cell Doses Are Associated with Decreased Relapse Rates

Abstract 

Peripheral blood stem cells (PBSC) have been increasingly used in the matched unrelated donor (MUD) transplant setting, but the impact of CD34⁺ cell dose on outcomes in this setting have not been well characterized. We analyzed 181 consecutive patients who underwent MUD-PBSC transplantation at the City of Hope between August 2000 to December 2004. Patients were conditioned with either full-intensity regimen or reduced-intensity regimen. There was a significant inverse relationship between higher CD34⁺ cell dose and faster neutrophil engraftment (r = −0.16, P = .035). By univariate analysis, a CD34⁺ cell dose ≥4.2 × 10⁶/kg (above the lowest quartile) was associated with significantly lower relapse risk (hazard ratio [HR] = 0.67, P = .0126), with a trend for corresponding improvement for disease-free survival (HR = 0.84, P = .12) but not overall survival (HR = 0.91, P = .46). The impact of the CD34⁺ cell dose remained significant in multivariate analysis. The higher CD34⁺ cell dose was significantly associated with faster recovery of absolute lymphocyte counts on day +30 posttransplant. Subset analysis demonstrated that the higher CD34⁺ cell dose was associated with (1) greater reduction in relapse in myeloid malignancies than that in lymphoid malignancies, (2) greater reduction in reduced-intensity conditioning than in full-intensity conditioning, (3) greater reduction in relapse when there is a inhibitory killer-cell immunoglobulin-like receptor ligand (iKIRL)-mismatch in the gravft-versus-host (GVH) direction, and (4) greater reduction in relapse when there is a lack of iKIRL, suggesting that the protective effect of CD34⁺ cell dose against relapse may be immune-mediated, possibly through NK cell recovery.

Key Words: Unrelated donor, Peripheral blood hematopoietic cell transplantation, CD34⁺ cell dose