scholarly journals Evaluation of Cord Blood (CB) TNC & CD34+ Cell Content, Cell Dose & Donor-Recipient 8-Allele HLA-Match By Patient Ancestry: An Analysis of 544 Units in a Racially & Ethnically Diverse Patient Population

2019 ◽  
Vol 25 (3) ◽  
pp. S209-S210
Author(s):  
Christopher Mazis ◽  
Ioannis Politikos ◽  
Sean M. Devlin ◽  
Molly A. Maloy ◽  
Kristine Naputo ◽  
...  
2020 ◽  
Vol 26 (4) ◽  
pp. 734-744 ◽  
Author(s):  
Juliet N. Barker ◽  
Christopher M. Mazis ◽  
Sean M. Devlin ◽  
Eric Davis ◽  
Molly A. Maloy ◽  
...  
Keyword(s):  

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3549-3549
Author(s):  
Robert Chow ◽  
B.C. Wang ◽  
Dennis Chou ◽  
Allen Lin ◽  
Judy Kang ◽  
...  

Abstract Abstract 3549 Cord blood potency is important for transplantation product selection, and various tests have been proposed to measure potency and predict engraftment potential, such as total nucleated cell dose (TNC), CD34+ cell dose (CD34), and colony forming unit dose (CFU). Though TNC has been the most widely used measure for CB selection to date, its predictive value is not as robust as the progenitor cell measurements. Unfortunately, most progenitor cell tests suffer from high inter-bank/laboratory coefficient of variance (CV) - decreasing the clinical utility of these tests as potency measures. Recently, the Duke Group proposed a CB APGAR scoring system composed of (1) a Pre-Cryopreserved Score (PCS) reflecting pre-freeze TNC, CD34, CFU and CB collected volume, as well as a (2) Composite Score (CS) which combines the PCS score with post-thaw TNC, CD34, CFU and mononuclear cell dose (MNC). Based on single, myeloablative and first transplants of mostly pediatric patients performed at a single institution (Duke) and using largely red cell reduced CB, the PCS and CS scores have been shown to be predictive of neutrophil and platelet engraftment probability. With CIBMTR-audited outcome data of transplanted CB products from a large multi-national CB bank, we sought to validate the CB APGAR system (1) on a patient population made up of mostly adults, (2) with heavy representation of minority and international patients, (3) on both single myeloablative and first transplants, as well as (4) other types of transplants, and lastly (5) using plasma depleted (red cell replete) CB products. The table below shows the day 42 neutrophil engraftment probability (ANC500) comparison of the original Duke data with StemCyte transplants using PCS and CS scores for both single, myeloablative and first transplants (SMF) and all transplants (All). For each of the PCS and CS strata that were compared, neutrophil engraftment probability appeared to be similar among the Duke SMF, StemCyte SMF and StemCyte All cohorts. We conclude that the Duke CB APGAR score, especially the PCS score, may serve as an easy-to-use and reproducible potency measurement that is highly predictive of neutrophil engraftment probability for (1) red cell reduced as well as plasma depleted CB, (2) for pediatric patient population as well as for mixed populations of adults and children, and (3) for minority and international patients. Lastly, the CB APGAR appears to be applicable to cord blood units with or without RBC depletion providing a tool that can be used for units processed and stored by various methods at different cord blood banks. Duke SMF StemCyte SMF StemCyte All Pre-Cryopreserved Score ANC500 ANC500 ANC500 PCS Score ≥ 7.75 93.1% (86.0–100%) 100 + 18.5%(n=4) 83.3 ± 19.4%(n=6) PCS Score < 7.75 74.7% (68.6–80.8%) 77.9 ± 8.6%(n=51) 76.0 ± 4.2%(n=215) Hazard Ratio (PCS≥7.75 vs <7.75*) 2.44 (1.78–3.59) 2.43 (0.85–6.95) 1.92 (0.78–4.68) Composite Score ANC500 ANC500 ANC500 CS Score ≥ 13.5 89.6% (83.9–95.3%) 93.8 + 13.8%(n=16) 84.4 ± 10.8%(n=32) CS Score < 13.5 69.3% (60.7–77.9%) 68.4 ± 12.4%(n=19) 77.1 ± 5.8%(n=109) Hazard Ratio (CS≥13.5 vs <13.5*) 2.31 (1.73–3.08) 1.54 (0.73–3.26) 1.19 (0.78–1.82) * Reference Disclosures: Chow: StemCyte: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Wang:StemCyte: Consultancy, Equity Ownership. Lin:StemCyte: Employment. Kang:StemCyte: Employment. Petz:StemCyte: Employment, Equity Ownership. Kurtzberg:StemCyte: Consultancy.


Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2717-2722 ◽  
Author(s):  
Anna Rita Migliaccio ◽  
John W. Adamson ◽  
Cladd E. Stevens ◽  
N. Ludy Dobrila ◽  
Carmelita M. Carrier ◽  
...  

There is evidence that the total cellular content of placental cord blood (PCB) grafts is related to the speed of engraftment, though the total nucleated cell (TNC) dose is not a precise predictor of the time of neutrophil or platelet engraftment. It is important to understand the reasons for the quantitative association and to improve the criteria for selecting PCB grafts by using indices more precisely predictive of engraftment. The posttransplant course of 204 patients who received grafts evaluated for hematopoietic colony-forming cell (CFC) content among 562 patients reported previously were analyzed using univariate and multivariate life-table techniques to determine whether CFC doses predicted hematopoietic engraftment speed and risk for transplant-related events more accurately than the TNC dose. Actuarial times to neutrophil and platelet engraftment were shown to correlate with the cell dose, whether estimated as TNC or CFC per kilogram of recipient's weight. CFC association with the day of recovery of 500 neutrophils/μL, measured as the coefficient of correlation, was stronger than that of the TNC (R = −0.46 and −0.413, respectively). In multivariate tests of speed of platelet and neutrophil engraftment and of probability of posttransplantation events, the inclusion of CFC in the model displaced the significance of the high relative risks associated with TNC. The CFC content of PCB units is associated more rigorously with the major covariates of posttransplantation survival than is the TNC and is, therefore, a better index of the hematopoietic content of PCB grafts.


2011 ◽  
Vol 121 (S5) ◽  
pp. S314-S314
Author(s):  
Jeffrey Cheng ◽  
Nancy Jiang ◽  
Benjamin Malkin

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3342-3342
Author(s):  
Christopher Mazis ◽  
Ioannis Politikos ◽  
Sean M Devlin ◽  
Molly Maloy ◽  
Eric Davis ◽  
...  

Abstract Introduction: Optimal CB unit selection guidelines recommend consideration of CD34+ cell dose & 8-allele donor-recipient HLA-match. How graft characteristics for these parameters vary by patient (pt) race/ ethnicity, however, is not known. Methods: We analyzed the infused graft & back-up unit cryopreserved total nucleated cell (TNC) x 107 & CD34+ x 105 cell content, the cell dose (incorporating pt weight), & 4-6/6 & 8-allele HLA-match by pt ancestry in CB transplant (CBT) recipients transplanted 1/2014-6/2018. Units were chosen based on banking practices (e.g. RBC depleted, standard cryo volumes), TNC & CD34+ dose & 4-6/6 & 8-allele HLA-match with dose usually taking priority over match given pt size at our center. The analysis included transplanted units (considered the best choice) & the next best high resolution typed back-up units (reserved but not shipped). Pt racial/ ethnic origins were prospectively obtained by detailed family history & grouped as previously described (Barker J. et al. BBMT 2010). Results: The characteristics of 513 units chosen for 136 CBT recipients by pt ancestry are shown (Table 1). Pts had highly diverse origins including 70 (51%) non-Europeans. The 513 units included 270 units infused as the graft (134 doubles & 2 singles) & 243 back-up units (109 pts had 2 back-ups, 25 pts had one & 2 had none). Thus, 4 best units were analyzed in 109 pts (all double unit recipients), 3 best in 25 pts (all doubles), & 1 unit in 2 pts (both singles). The median weight of the 136 pts was 81 kg. Asian pts (median 68 kg) had a lower weight than other groups. The median TNC content of units for the 66 European pts was higher than that for the 70 Non-Europeans (218 vs 196, p = 0.004). Units chosen for Northwestern (NW) Europeans had the highest median TNC content (235) with lower TNC content in units for Southern Europeans (202), Asian (193), African (191) & White Hispanic (189) pts. Units chosen for European pts also had a higher median CD34+ cell content (162) than Non-Europeans (138), p = 0.004. NW Europeans had units with a higher median CD34+ content (198) & the lowest CD34+ content were those for African (124) & Middle Eastern pts (124). When patient weight was considered, median TNC/kg dose per unit was similar in European and Non-European pts (2.7 vs 2.6, p = NS). Units for NW Europeans had the highest median TNC dose (3.0) whereas those for African pts had the lowest TNC dose (2.4). Units for Europeans had a higher median CD34+ dose (2.0) than Non-Europeans (1.7) although this difference was not significant (p = 0.15). Additionally, similar to TNC dose, median CD34+ dose was highest in units for NW European pts (2.2) & lowest in units chosen for African pts (1.5). 89% of chosen units were 4/6 HLA-matched with no differences between Europeans & non-Europeans. Furthermore, the median 8 allele HLA-match was 5/8 (range 2-8/8) with no overall differences between units for Europeans and Non-Europeans (p = NS). When only transplanted units were analyzed (Table 2), the median TNC & CD34+ contents were significantly lower in non-Europeans than Europeans (238 vs 216, p = 0.01 & 184 vs 160, p = 0.016). Overall, however, units received by Europeans vs non-European pts had similar TNC & CD34+ doses (p = NS). However, differences in the CD34+ content combined with differences in pt weights resulted in disparities in CD34+ doses by ancestry sub-group. NW Europeans (high weight, high CD34+ content) received the best CD34+ doses; lower CD34+ content in Asian pts was compensated for by their lower weight. African pts (high weight, low CD34+ content) received the lowest CD34+ doses. The median 8 allele HLA-match for all was 5/8 (range 3-8/8) with the exception of African pts [median 4/8 (range 3-7/8)]. Moreover, while 108 (40%) of transplanted units were 3-4/8 HLA-matched overall, there were marked differences between pt sub-groups with only 23% of units for NW Europeans being 3-4/8 vs 42% for southern Europeans, 46% for white Hispanics & 53% for Africans. Conclusions: While CB significantly extends transplant access to racial & ethnic minorities, differences in cellular content translates to many minority pts receiving lower dosed units. There are also marked racial/ ethnic differences in HLA-match grade with African pts the most likely to receive highly mismatched units. This data supports ongoing funding of public CB banks to further increase the inventory of high dosed & better matched units for all but especially racial & ethnic minority pts. Disclosures Shah: Janssen: Research Funding; Amgen: Research Funding. Kernan:National Cancer Institute: Research Funding.


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