slide1
Download
Skip this Video
Download Presentation
Cord Blood (CB) Hematopoietic Progenitor Cell (HPC) Characterization and Correlation with Ethnicity: A Report From The C

Loading in 2 Seconds...

play fullscreen
1 / 26

Cord Blood (CB) Hematopoietic Progenitor Cell (HPC) Characterization and Correlation with Ethnicity: A Report From The C - PowerPoint PPT Presentation


  • 123 Views
  • Uploaded on

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, 2 E.L. Wagner, 3 J Fraser, 4 L Jensen, 2 S Carter, 5 N.A. Kernan, 6 J Kurtzberg

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Cord Blood (CB) Hematopoietic Progenitor Cell (HPC) Characterization and Correlation with Ethnicity: A Report From The C' - elam


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Cord Blood (CB) Hematopoietic Progenitor Cell (HPC) Characterization and Correlation with Ethnicity: A Report From The COBLT STUDY

1M S Cairo, 2G Cohen, 2E.L. Wagner, 3J Fraser, 4L Jensen, 2S Carter, 5N.A. Kernan, 6J Kurtzberg

1Georgetown University, Washington DC, 2The Emmes Corporation, Rockville MD, 3University of California Los Angeles, Los Angeles CA, 4National Heart, Lung and Blood Institute, Bethesda MD, 5Memorial Sloan Kettering Cancer Center, New York NY, 6Duke University Medical Center, Durham NC

introduction
Introduction
  • Advantages of CB and CBT

Ease and safe procurement Enriched HPC

Rapid availability Immaturity of T cell immunity

Decreased viral transmission Decreased severe AGVHD

Multi-ethnic representation Reduced chronic GVHD

  • Disadvantages of CB and CBT

Decreased supply Delay in hematopoietic recovery

Expensive to develop Prolonged immune reconstitution

Limited cell dose Lack of available cells for ACI

Genetic/infectious transmission Increased infectious morbidity

introduction3
Introduction
  • CB CD34+/kg graft content has been significantly correlated with engraftment and survival following UCBT

Wagner et al, Blood, 2002

Styczynski et al, BMT, 2004

  • CB vs BM CD34+/38- has a higher cloning efficiency, proliferate more rapidly and generate more HPC

Cardoso et al, PNAS, 1993

Hao et al, Blood, 1995

  • CB CD34+/CD90+ (Thy-1+) possess a high clonogenic cell expansion capacity and increased HPP-CFC

Mayani et al, Blood, 1994

  • PB CD34+/CD41+ (CD61+) subsets are significantly correlated with platelet recovery following Auto PBSCT

Derecksen et al, JCO, 1998

objectives
Objectives
  • To characterize processed CB HPC subsets including CD34+, CD34+/CD38-, CD34+/CD90+ and CD34+/CD61+
  • To correlate processed CB HPC subsets with in vitro CB HPC colony formation including total CFU, CFU-GEMM, CFU-GM and BFU-E
  • To determine the relationship of birth weight, gestational age, ethnicity, gender and type of delivery with processed CB HPC
cord blood banks data coordinating center and nhlbi
Cord Blood Banks, Data Coordinating Center and NHLBI

Cord Blood Bank

Duke University

J. Kurtzberg PI

COBLT Study Committee

N.A.Kernan, Chair/L Jensen, NHLBI

Data Coordinating Center (Emmes)

S. Carter & E.L. Wagner

Cord Blood Bank

Georgetown University

M.Cairo, PI

Cord Blood Bank

University of California, LA

J Fraser, PI

methods
Methods
  • Cord blood collection and processing were performed as described by COBLT

Fraser,Cairo, Kurtzberg J. Hematotherapy, 1998

  • Cord Blood CD34+ and CD34+ subset characterization (300-1200 events)
    • ProCount®/FACSort™ — Duke and UCLA
      • IgG1 FITC isotype control
    • ISHAGE/Epics XL-MCL —Georgetown University
      • IgG1 PE isotype control
methods7
Methods

* Duke & UCLA

methods8
Methods
  • In vitro HPC Colony Assays
    • Processed CB (1 x 105 nucleated cells /mL) in IMDM, 2% FBS in Methocult® media
    • Incubated at 37°C, 5% for 11-14 days in 24 well tissue culture plates.
  • BFU-E
    • Bright red ≥ 50 cells/burst, tightly packed, multicentered
  • CFU-GM
    • Colorless, granular, ≥ 30 cells/colony, dispersed formation
  • CFU-GEMM
    • “Fried egg” appearance, ≥ 40 cells/colony, compact, spherical hemoglobinized area at center or one side.
results
Results

Maternal Donor

Screened

34,799

(100%)

Long Term Storage

8,731

53% of Collections

45% Pregnancy related

29% Refused

9% Medical History

6% Risk Behavior

11% Other

Maternal Donor

Consented

20,710

(60%)

Low Counts

Poor Viability

Positive Culture

No HPC

Positive HGB Screen

44% No Staff

41% Exclusions

15% Other

Cryopreserved

11,077

(66%)

Total Collections

16,764

(81%)

64% CB Volume

11% +ID

7% History

18% Other

delivery gender gestational age birth weight
Delivery, Gender, Gestational Age, Birth Weight
  • Type of DeliveryGender
  • Vaginal 74% Males 52%
  • C-Section 26% Females 48%
  • Gestational Age (wks) Birth Weight (gms)
  • < 37 8% < 2500 1%
  • 38 17% 2501-3000 11%
  • 39 30% 3001-3500 37%
  • 40 31% 3501-4000 36%
  • 41 14% >4000 15%
representative flow cytometry dot plots of cd34 cd34 cd38 cd34 cd61 and cd34 cd90
Representative Flow Cytometry Dot Plots of CD34+, CD34+/CD38-, CD34+/CD61+ and CD34+/CD90+

CD34+

CD34+/CD38-

CD34+/CD61+

CD34+/CD90+

significant correlations of cb log cd34 vs cfu gm cfu gemm bfu e
Significant* Correlations of CB Log CD34+ vs 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

slide17
Positive Correlation of Log Total Nucleated Cell Count (TNCC) with Log CD34+ Count in COBLT Processed Cord Blood
slide20
63

53

21

44

44

14

White African American Asian Hispanic Other

White African American Asian Hispanic Other

Other

Other

White

White

Black

Black

Asian

Asian

Hispanic

Hispanic

Significant* Reduction in CB CD34+/CD38- and CD34+/CD61+ in African Americans & Asians vs Caucasians & Hispanics

CD34+/CD38-

CD34+/CD61+

* All p<0.001

correlation of cb hpc with birth weight and gestational age
Correlation of CB HPC with Birth Weight and Gestational Age

Birth Weight

Gestational Age

CD34+/CD61+

CD34+/CD61+

CD34+/CD38-

CD34+/CD38-

summary
Summary
  • 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+)
summary24
Summary
  • 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.
speculation
Speculation
  • 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.
acknowledgments
Acknowledgments
  • 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
ad