Engraftment Rate and Kinetics Following Umbilical Cord Blood Transplantation Is Critically Affected by CD34+ Progenitor Cell Dose and CD8+ T-Cell Dose Complementary.

Abstract

<Background> The risk of rejection after umbilical cord blood (CB) transplantation (CBT) is substantially higher than that after allogeneic BMT or PBSCT. In CBT, higher total nucleated cell count and CD34+ cell dose are shown to be associated with significant rapid and proper engraftment. Although CD8+ or other accessory cells are shown to have positive association with engraftment in many experimental and clinical BMT, potential contribution of these cells to engraftment after CBT has not been examined comprehensively.<Patients and methods> We examined CB subpopulation doses, such as CD34+, CD3+, CD4+, CD8+, CD14+ and CD16/56+ cells, in cryopreserved CB unit by flowcytometry, and analyzed their influence on the risks of primary graft-failure, GVHD, non-relapse mortality and the probability of survival. Data on 146 patients [median age 15.0 years old (range, 0.2–74.0), median body weight 41.0 kg (range, 4.8–85.0)] who received CBT as their first transplant between 1995 and 2002 for the treatment of malignant (n=137), including advanced disease patients (n=100), and nonmalignant (n=9) diseases were evaluated. The HLA-disparity between CB and patient was 0/6: 35 (24.0%), 1/6: 65 (44.5%), 2/6: 45 (30.8%), and 3/6: 1 (0.7%).<Results> In a multivariate analysis, CD34+ cell dose at higher than the median (>1.4 × 105/kg) and CD8+ cell dose at higher than the median (>15.7 × 105/kg) were significantly associated with successful engraftment [Hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37–0.85, and HR, 0.65; 95% CI, 0.43–0.99, respectively]. In the subgroup of CD34+ cell higher than the median group, the median time to achieve neutrophil engraftment was comparable between CD8+ higher and lower than the median group (21 days and 22 days, P=0.11). In the subgroup analysis for patients who received lower than the median (1.4 × 105/kg) of CD34+ cells, the median time to achieve neutrophil engraftment in the patients received more CD8+ cells (>15.7 × 105/kg) was significantly faster than that in the patients received less CD8+ cells (21 days versus 25 days, P=0.0047). CD8+ cell dose in at least median and HLA-disparity more than 1 locus were significant factors associated with an increasing incidence of grade II–IV acute GVHD [HR, 2.05; 95% CI, 1.18–3.59 and HR, 2.41; 95% CI, 1.16–5.00, respectively]. We could not detect any association of higher CD34+ and CD8+ cell doses with improved survival. No significant impact of other CB subpopulations on transplant outcome was observed.<Discussion> Our findings and previous study reported by Wagner et al. (Blood. 2002; 100:1611–8) demonstrated the CD34+ cell dose in CB unit is a significant and definitive predictor of engraftment rate and kinetics after CBT, and suggested the threshold dose for successful engraftment is around 1.4–1.7 × 105/kg. Additionally, CD8+ cells may have a supportive role in engraftment following CBT with an insufficient CD34+ cell dose. To confirm the effect of these cell subpopulations on survival, further study with more monotonous background is warranted.