The Cord Blood Apgar: a novel scoring system to optimize selection of banked cord blood grafts for transplantation (CME)

Abstract

BACKGROUND Engraftment failure and delays, likely due to diminished cord blood unit (CBU) potency, remain major barriers to the overall success of unrelated umbilical cord blood transplantation (UCBT). To address this problem, we developed and retrospectively validated a novel scoring system, the Cord Blood Apgar (CBA), which is predictive of engraftment after UCBT. STUDY DESIGN AND METHODS In a single-center retrospective study, utilizing a database of 435 consecutive single cord myeloablative UCBTs performed between January 1, 2000, to December 31, 2008, precryopreservation and postthaw graft variables (total nucleated cell, CD34+, colony-forming units, mononuclear cell content, and volume) were initially correlated with neutrophil engraftment. Subsequently, based on the magnitude of hazard ratios (HRs) in univariate analysis, a weighted scoring system to predict CBU potency was developed using a randomly selected training data set and internally validated on the remaining data set. RESULTS The CBA assigns transplanted CBUs three scores: a precryopreservation score (PCS), a postthaw score (PTS), and a composite score (CS), which incorporates the PCS and PTS values. 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) engraftment. Likewise, CBA-PTS and CS scores were strongly predictive of Day 42 neutrophil engraftment (CBA-PTS ≥ 9.5 vs. <9.5, HR 3.16, p < 0.0001; CBA-CS ≥ 17.75 vs. <17.75, HR 4.01, p < 0.0001). CONCLUSION The CBA is strongly predictive of engraftment after UCBT and shows promise for optimizing screening of CBU donors for transplantation. In the future, a segment could be assayed for the PTS score providing data to apply the CS for final CBU selection.

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

“…However, in contrast to the other cell sources, unmanipulated CB hematopoietic stem and progenitor cells (HSPCs) demonstrate defective CXCL12-mediated homing and adhesion to endothelium and delayed hematological engraftment and reconstitution [5][6][7]. Higher HSPC dosages, measured in terms of colony forming unit (CFU) content and ‡1.8 · 10 5 viable CD34 + cells transplanted per kilogram of the recipient's body weight in this respect, seem needed to improve the median time and probability of neutrophil and platelet engraftment, factors essential for reducing transplant-related morbidity and mortality [8][9][10][11][12][13][14][15][16][17].…”

Hematopoietic Stem Cell Potency for Cellular Therapeutic Transplantation

“…From a practical viewpoint, a cord blood potency determination would be performed on the limited number of cells thawed in a segment used for confirmatory testing prior to the cord blood unit being transplanted. Several publications have shown, using TNC, viability, CD34 and CFU, that segments of cryopreserved cord blood used for confirmatory testing are a representative sample of the cells in the cord blood unit (Goodwin et al 2003;Solves et al 2004, Rodriguez et al 2005Page et al 2011b). However, in all of these cases, the potency of the active ingredients, i.e.…”

“…Although the number of UCB transplants has increased almost exponentially since the first published UCB transplant in 1989 (Gluckman et al 1989), approximately 20% of patients receiving an unrelated UCB transplant exhibit graft failure (Page et al 2011a(Page et al , 2011b. This has, in part, been attributed to inadequate UCB potency (Page et al 2011a(Page et al , 2011b.…”

“…This has, in part, been attributed to inadequate UCB potency (Page et al 2011a(Page et al , 2011b. Previous publications have focused on the need for standardized laboratory procedures (Rich, 1997;Wagner E et al 2006;Brand A et al 2008).…”

“…This has been the functional assay used previously in hematopoietic stem cell processing laboratories and is still used by the cord blood community today. More recently, the CFU assay has been suggested as a potency assay (Page et al 2011a(Page et al , 2011b, in addition to other parameters normally measured. These include total nucleated cell count (TNC), viability and CD34 membrane expression (FDA, 2009).…”