A Novel Scoring System, the Cord Blood Apgar, Predicts Engraftment After Cord Blood Transplantation: Optimization of Selection of Cord Blood Units (CBUs) for Transplantation

Using current graft selection criteria, primary graft failure and engraftment delays are major obstacles to the overall success of unrelated donor umbilical cord blood (CB) transplantation (CBT). Up to 20% of patients receiving a CBT experience primary graft failure resulting in part from inadequate potency of their donor cord blood unit (CBU). In this single center retrospective study, we describe correlations of graft parameters with engraftment and present a novel scoring system, the Cord Blood Apgar (CBA) to optimize graft selection for CBT.

The CBA was developed utilizing a database created from 435 consecutive single cord myeloablative transplants performed at Duke between 1/1/2000 and 12/31/2008. Correlations of pre-cryopreservation (pre-cryo) and post-thaw graft parameters (TNC, CD34, CFU, volume collected and MNC) with time to engraftment were analyzed. Based on the hazard ratio magnitude of each graft parameter in the univariate analysis of time to neutrophil engraftment, a weighted scoring system was developed and internally validated using independent training and testing datasets. Transplanted CBUs were assigned two scores: a Pre-cryo Score (PCS) using pre-cryo characteristics alone and a Composite Score (CS) based on combined pre-cryo and post-thaw graft characteristics.

The overall cumulative incidences of neutrophil (day +42) and platelet (day +180) engraftment were 76.9% and 55%, respectively. CBA-PCS scores, which could be used for initial unit selection, were predictive of neutrophil (CBA-PCS≥7.75 vs. <7.75: HR=3.5, p<0.0001) and platelet engraftment (CBA-PCS≥7.75 vs. <7.75: HR=1.8, p=0.003). The cumulative incidence of neutrophil engraftment (day+42) for patients transplanted with CBUs receiving CBA-PCS ≥7.75 was 93.1% (95% confidence interval (CI) 86–100%) compared to 74.7% (95%CI 68.6–80.8%) for CBU scoring <7.75 with a median 19 vs. 28 days, respectively. Likewise, CBA-CS scores, which could be determined using post-thaw parameters measured on an attached segment before unit release, were strongly predictive of neutrophil (CBA-CS≥17.75 vs. <17.75: HR=4.01, p<0.0001) and platelet engraftment (CBA-CS≥17.75 vs. <17.75: HR=1.74, p=0.006). The cumulative incidence of neutrophil engraftment at day +42 was 96.6%(95%CI 90.9–100%) for patients transplanted with CBU-CS ≥17.75 compared to 73.7% (95%CI 67.0–80.4%) with a median 19 vs. 29 days, respectively. In multivariate analysis including clinical factors, the CBA-PCS and CS were the strongest predictors of neutrophil engraftment (both p<0.0001) and significant predictors of platelet engraftment (PCS p=0.01, CS p=0.003). The risk of graft failure was also strongly predicted by the CBA-PCS (PCS ≥7.75 vs. <4.25: HR=0.14, p=0.013) with a probability of non-engraftment at day 42 for PCS ≥7.75 vs. <4.25 of 0.07 and 0.32, respectively. Other scoring systems were tested but not shown to be superior to the CBA.

The CBA is strongly predictive of engraftment after CBT and can be utilized for donor selection for search and release of CBUs. This should be validated in a prospective multi-institutional study.

Gentry:Aldagen, Inc: Employment. Balber:Aldagen, Inc: Employment.