Cord Blood (CB) Hematopoietic Cord Blood (CB) Hematopoietic Progenitor Cell (HPC) Progenitor Cell (HPC) Characterization and Correlation Characterization and Correlation with Ethnicity: A Report From The with Ethnicity: A Report From The COBLT STUDY COBLT STUDY 1 M S Cairo, 2 G Cohen, 2 E.L. Wagner, 3 J Fraser, 4 L Jensen, 2 S Carter, 5 N.A. Kernan, 6 J Kurtzberg 1 Georgetown University, Washington DC, 2 The Emmes Corporation, Rockville MD, 3 University of California Los Angeles, Los Angeles CA, 4 National Heart, Lung and Blood Institute, Bethesda MD, 5 Memorial Sloan Kettering Cancer Center, New York NY, 6 Duke University Medical Center, Durham NC
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Cord Blood (CB) Hematopoietic Progenitor Cell (HPC) Characterization and Correlation with Ethnicity: A Report From The COBLT STUDY 1 M S Cairo, 2 G Cohen,
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Total Mononuclear cells 4.7 x 108 3.8 x 108 (-19%)
Total CD34+ NA 3.4 x 106
Gate: CD34+
Gated Events: 908
Total Events: 6808
Gate Events % Gated
G1 908 100.00
G2 908 100.00
CD45+ 907 99.89
34+ Subset - 871 95.93
Dual + 1 0.11
CD34+ 908 100.00
R4
R5
Gate: CD34+
Gated Events: 905
Total Events: 7634
Gate Events % Gated
G1 905 100.00
G2 905 100.00
CD45+ 904 99.89
34+ Subset - 22 2.43
Dual + 72 7.96
CD34+ 905 100.00
R4
R5
Representative Flow Cytometry Dot Plots of Representative Flow Cytometry Dot Plots of CD34CD34++, CD34, CD34++/CD38/CD38--, CD34, CD34++/CD61/CD61++ and and
Significant Correlation of CB Log Significant Correlation of CB Log CD34CD34++ vs Log Total CFU vs Log Total CFU
Log CD34+ (x 104)
Lo
g A
ll C
FU
(x
104 )
Significant* Correlations of CB Log CD34Significant* Correlations of CB Log CD34++ vs CFU-GM, CFU-GEMM & BFU-Evs CFU-GM, CFU-GEMM & BFU-E
CD34+ vs CFU-GM CD34+ vs CFU-GEMM CD34+ vs BFU-E
r = 0.68
P = 0.000
n = 8696
r = 0.52
p = 0.000
n = 4189
r = 0.61
p = 0.000
n = 8689
* All p<0.001
Positive Correlation of Log Total Nucleated Positive Correlation of Log Total Nucleated Cell Count (TNCC) with Log CD34Cell Count (TNCC) with Log CD34++ Count in Count in
Significant* Correlations of CB Log Significant* Correlations of CB Log CD34CD34++ subsets with Log CFUs subsets with Log CFUs
Log CD34+/CD61+ Log CD34+/CD38- Log CD34+/CD90+
N R N R N R
Log Total CFU 5073 0.55 5048 0.33 3600 0.30
Log Total BFU-E 5069 0.49 5045 0.31 3597 0.27
Log Total
CFU-GM5075 0.51 5050 0.35 3600 0.27
Log Total
CFU-GEMM2689 0.41 2684 0.27 2281 0.26
* All p<0.001
Significant* Correlations of CB Log Significant* Correlations of CB Log CD34CD34++ Subsets with Each Other Subsets with Each Other
Log CD34+ Log CD34+/CD38-
Log CD34+/CD61+
Log CD34+/CD90+
Log CD34+ 1.00 0.69 0.64 0.47
Log CD34+/CD38- 0.69 1.00 0.35 0.40
Log CD34+/CD61+ 0.64 0.35 1.00 0.47
Log CD34+/CD90+ 0.47 0.40 0.47 1.00
* All p<0.0001
Significant* Reduction in CB CD34Significant* Reduction in CB CD34++/CD38/CD38-- and CD34and CD34++/CD61/CD61++ in African Americans & in African Americans &
Asians vs Caucasians & HispanicsAsians vs Caucasians & Hispanics
* All p<0.001
CD34+/CD38- CD34+/CD61+
White Black Asian Hispanic Other White Black Asian Hispanic Other
53
44
White African American Asian Hispanic Other White African American Asian Hispanic Other
63
44
21
14
Correlation of CB HPC with Birth Weight Correlation of CB HPC with Birth Weight and Gestational Ageand Gestational Age
Significant Correlation of CB HPC Significant Correlation of CB HPC with Delivery and Genderwith Delivery and Gender
Delivery Gender
C-Section vs Vaginal Male vs Female
Total CFU
+ 8.7% (5.8-11.7)
CD34+/CD61+
+ 6.5% (0.4-13.0)
p <0.001 p <0.035
SummarySummary
• Post processing CB log CD34+ was significantly correlated with log total CFU, BFU-E, CFU-GM and CFU-GEMM
• Post processing CB log CD34+ subsets (CD38-, CD61+, CD90+) were significantly correlated with log total CFU, BFU-E, CFU-GM and CFU-GEMM
• Post processing CB log CD34+ subsets were significantly correlated with each other (CD34+/CD38-, CD34+/CD61+, CD34+/CD90+)
SummarySummary
• African-American and Asian donors were associated with significantly less CD34+/CD38- and CD34+/CD61+ processed CB HPC subsets
• C-section delivery was significantly associated with increased total processed CB CFU
• Male gender was significantly associated with increased CB CD34+/CD61+ HPC subset
• Birth weight was significantly correlated with both CD34+/CD38- and CD34+/CD61+ and inversely correlated with gestational age.
SpeculationSpeculation
• Post processing CB HPC CD34+ subsets and/or in vitro CB HPC CFUs may potentially correlate with the kinetics of lineage specific CB engraftment post CBT
• Ethnicity, gender, delivery, birth weight and /or gestational age may have a significant effect on CB HPC and therefore, may be a factor in the future selection of a processed CB unit for CBT
• The current COBLT UCBT study will determine the
significance of these observations.
AcknowledgmentsAcknowledgments
• NHLBI Support
• N01-HB-67136, N01-HB-67142, N01-HB-67132 and
N01-HB-67141
• Cord Blood collection, processing and flow cytometry
personnel at Carolina, UCLA and Georgetown University
Cord Blood Banks
• Maternal donors and newborns for their public generosity