Cord Blood (CB) APGAR Score Is Predictive of Neutrophil Engraftment and Graft Failure Probabilities for Plasma Depleted/Reduced CB Products

Nucleated cell (NC), CD34+ cell (CD34), and colony forming unit (CFU) doses have been proposed to measure CB potency - important for engraftment potential prediction and transplantation product selection. Though TNC is widely used for CB selection, its predictive value is not as robust as the progenitor cell measurements. CFU and CD34 suffer from high inter-laboratory coefficient of variance (CV) - decreasing the clinical utility as potency measures. Recently, the Duke Group proposed a CB APGAR scoring system composed of (a) a Pre-Cryopreserved Score (PCS) reflecting pre-freeze CFU, CD34, NC, and CB collected volume, as well as a (b) Composite Score (CS) which combines the PCS score with post-thaw NC, CD34, CFU and mononuclear cell dose. Based on single, myeloablative and first (SMF) transplants of largely pediatric patients performed at Duke and using mostly red cell reduced (RCR) CB, the PCS and CS scores were shown to be predictive of graft failure, neutrophil and platelet engraftment. With CIBMTR-audited outcome data of transplanted CB products from a multi-national CB bank, we sought to validate the CB APGAR system on a patient population with mostly adults, heavy representation of minority and international patients, and on both SMF transplants, and all transplants (All) using plasma depleted/reduced (PDR) CB products. The PCS and CS table below shows the day 42 neutrophil engraftment cumulative incidence (ANC500) and graft failure probability (GF) comparisons of the Duke data with PDR transplants for both SMF and All transplants. For each of the PCS and CS strata compared, ANC500 and GF appeared to be similar among the Duke SMF, StemCyte SMF and All cohorts. We conclude that the CB APGAR score, especially the PCS, is an easy-to-use and reproducible potency measurement for CB selection by transplant centers that is highly predictive of ANC500 engraftment and GF for (1) RCR as well as PDR CB, (2) for mostly pediatric patient population as well as for mixed populations of adults and children, and (3) for minority and international patients. Whether the method can be applied to double, non-myeloablative and repeat CB transplants remains to be seen. Lastly, for the same PCS or CS strata, PDR CB appear to have similar engraftment and GF probabilities as RCR CB; therefore, the Duke CB APGAR is applicable to CB products with or without RBC reduction and reflects potency of CB products processed and stored by various methods at different CB banks.Table 1ANC 500 Engraftment Cumulative Incidence & Graft Failure ProbabilitiesANC 500Duke SMFPDR SMFPDR AllPCS≥7.7593% (86-100%)100±18%83±19%PCS<7.7575% (69-81%)78±9%76±4%HR2.44 (1.78 - 3.59)2.43 (0.85 - 6.95)1.92 (0.78 - 4.68)CS≥13.590% (84 - 95%)94±14%84±11%CS<13.569% (61 - 78%)68±12%77±6%HR2.31 (1.73 - 3.08)1.54 (0.73 - 3.26)1.19 (0.78 - 1.82)Graft Failure ProbabilityDuke SMFPDR SMFPDR AllPCS≥7.757% (3-17%)0±18%17±19%PCS≥5.5 & <7.7519% (12-30%)15±14%18±10%PCS≥4.25 & <5.526% (16-39%)6±13%14±9%PCS<4.2532% (22-45%)38±12%29±5% Open table in a new tab