Higher Infused CD34+ Dose Positively Influence Platelet Recovery After Cord Blood Transplantation

Background: Umbilical cord blood transplantation (UCBT) is associated with delay in platelet recovery. However, the underlying factors influencing this delayed recovery remain poorly understood. With the aim of identifying factors that influence platelet engraftment, we retrospectively analyzed data from 68 consecutive myeloablative UCBT recipients transplanted between April 2006 and March 2012. Methods: Forty-two (62%) patients received high-dose TBI (1320 cGy), cyclophosphamide and fludarabine (FLU); while 26 (38%) received Treosulfan, FLU, and a single fraction of 200cGy TBI. Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. Platelet recovery was defined as the first day of a platelet count ≥20 and ≥50 x 10⁹/L without transfusion for 7 days.  Cumulative incidence (CI) curves were used to estimate the probabilities of platelet engraftment in the first 100 days post- transplant. A proportional hazards regression model was used to evaluate the association between CD34⁺ cell dose and platelet engraftment. Factors considered as potential predictors or confounders included age at transplant, sex, race, body mass index (BMI), disease risk, CMV seropositivity, presence of minimal residual disease at transplant (MRD), number of UCB units infused, acute GVHD, total nucleated cells (TNC) and CD34⁺ cells. Results: Median age and BMI were 36 years (range, 1-63) and 26 kg/m² (range, 16-41), respectively. The majority of patients (88%) received 2 cord blood units (n=60). Twenty-seven (40%) had MRD and 46 (68%) were CMV seropositive at time of transplant. Median total infused cell doses were:  3.9 x 10⁷ TNC/kg (range: 2.2-11.2) and 0.25 x 10⁶ CD34⁺ cells/kg (range: 0.09 – 1.46). The 100-day CI of platelet engraftment was 65% (95% CI: 53-76%) for platelets ≥20 10⁹/L and 59% (95% CI: 47-71%) for platelets ≥50 10⁹/L. In univariate analysis higher CD34⁺ infused dose was significantly associated with platelet engraftment [HR=1.4 (95% CI: 1.0-1.9, p=0.03)]. Furthermore, platelet engraftment was suggestively slower among patients with higher BMI [HR=0.9 (95% CI: 0.9-1.0, p=0.06)] while presence of aGVHD grade III-IV was associated with higher rate of engraftment [HR=2.1 (95% CI: 0.8-5.9, p=0.07)]. No significant associations were found between all the others factors analyzed and platelet recovery.In multivariable analysis the association between larger CD34⁺ dose and higher rate of engraftment remained statistically significant [HR=1.9 (95% CI: 1.3-2.8, p<0.001]. In addition, CMV seropositivity [HR=0.4 (95% CI: .0.2-0.9, p=0.02)] became significantly associated with a slower rate of engraftment. Conclusions: These results indicate that the infused CD34⁺ dose is a strong independent predictor of platelet engraftment. Furthermore we should expect an earlier sustained platelet recovery among CMV seronegative patients.