Public Cord Blood Banking at the National Cord Blood Program (NCBP)

Public Cord Blood Banking at the

National Cord Blood Program (NCBP)

A. Scaradavou, MD

Medical Director, National Cord Blood Program, New York Blood Center

Associate Attending, Pediatric BMT Memorial Sloan-Kettering Cancer Center

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CB as hematopoietic stem cell graft

• The blood remaining in the placenta and umbilical cord after the birth of baby is rich is hematopoietic stem cells

• This blood can be harvested easily, with no risk to the mother or baby



Advantages of CB in transplantation

 Easy access – large numbers of donors – ethnic diversity  Can be collected and stored (cryopreserved) in CB Banks

 Available upon demand – no delays in transplants  Lower risk of viral infections

 Immunologically “naïve” T cells: do not need “perfect” match



Considerations

 Transmission of (unknown) diseases

Background: CB Collection Models

 In Utero Collection: after delivery of newborn; placenta still in utero

 Ex Utero Collection: placenta delivered and removed from delivery room; collection performed by trained technologists

CB collection “kit” Ex utero CB collection

Placenta

Umbilical Cord

Cord Blood Unit

Cord Blood Collection (NCBP)

 Ex utero collection

 Trained collection personnel

 TNC count at collection - Identification of clinical units

 Maternal Consent - sample - Questionnaire - Records

 Transportation to the Bank - temperature monitoring

Time from collection to

completion of processing: maximum 36 hours

What is a “bankable” CBU

 “Adequate” TNC (volume): above Bank’s “cut-off”

 Not Clotted

 Maternal informed consent – medical information

 No Contamination with Bacteria/Fungi

 No Contamination with Mother’s Blood

 Processed within 36 hours* from collection

 Adequate / Viable Hematopoietic Progenitor Cells

 Complete infectious disease testing

*FACT requires

maximum of 48 hrs from collection

Background:

CB Processing Methods

• Manual or Automatic Processing

• Closed System or Open System

• Volume Reduction Only

• Red Cell Depletion Only

AXP: Automated Processing System

 Partial RBC depletion and volume reduction

 Closed manufacturing system; Aseptic processing

 Accurate final product volume; Consistent, low hematocrit

 High recovery of mononuclear and CD34+ cells; excellent viability

Cord Blood Processing (NCBP)

Plasma

RBCs

Cord Blood freezing and storage

Two-compartment Cryopreservation Bag; total volume: 25 mL HPC-C cryoprotected in DMSO; final DMSO concentration: 10%

1 2

Segments: identity and potency testing post-cryopreservation

1: HLA Confirmatory Typing; 2: CD34+ count/viability, CFU testing 3: retention sample

CB storage

Individual CBU:

 controlled rate freezing (CRF)  long-term storage in liquid nitrogen in the same freezer  reduced transient warming events

 automated retrieval Standardization:

 highly reproducible

cryopreservation profiles  computerized system

Cord Blood cryopreservation - storage

Capacity: 3600 HPC, Cord Blood products BioArchive

Cord Blood Testing











performed prior to transplant

0 500 1000 1500 2000 2500

0 200 400 600 800 1000

Potency: CFU counts and vCD34+ cells

vC

D3

4/mL

10

^3

CFU/ mL 10^3

R²= 0.76 Y=1.4x + 0.86

The “life cycle” of a clinical CBU

Harvest CB TNC

Label CBU - Clinical - Informed consent –

maternal questionnaire

Testing: Potency, IDMs, eligibility, HLA, other QA Review: CBU Release to Search (status)

Research CBU No identifiers No further tests

Review for patient: TNC/match HLA CT from segment

CBU Release for Transplant

Processing - Cryopreservation - Freezing Total Nucleated Cell count at collection

Cord Blood Shipping - Transportation

CB Unit

Shipping Container

< -150C for 5-7 days

CryoShipper Lid CB Unit

Shipping container Continuous temperature

monitoring during transportation

-190° C

NCBP HPC, Cord Blood: final product

Highly regulated stem cell source

Accreditations: FACT or AABB

HEMACORD: NCBP FDA licensed product

November 2011: First stem cell product to be licensed

Stability studies of CB products:

a) Does the “time in storage” affect potency or engraftment ability

b) Is there an expiration date for the products?

HPC, Cord Blood Stability Studies

Example: Labeling

Manufacturing – Expiration Date

NEW CONTAINER LABEL APPLIED AT SHIPMENT

“PARTIAL” LABEL

PRINTED AT SHIPMENT

EXPIRATION DATE PRODUCT NAME

Access to the NCBP CB Inventory

NCBP’s Web portal: WebSearch Registries:

•

NW Eu rope

Easte rn Eu

rope NW Eu

rope

Easte rn Eu

rope

Unrelated Donor Searches: Results based on patient Ancestry

CB extends transplant access to patients of ethnic “minorities”

Barker et al, BBMT 2010; 16(11):1541-1548

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Search, Evaluation and Acquisition of CBU for

unrelated transplantation

 Well trained, dedicated transplant search coordinators

 Clear, step-by-step procedures for search, evaluation and CBU selection for transplant

 Communication between search coordinators, clinical teams and Stem Cell Lab

TNC dose; CD34+ cell dose and viability, CFU assays

Interaction of TNC - HLA match

Allele level matching (HLA-A, -B, -C, -DRB1) Selection of CBU with permissible mismatches

Standardization of banking practices

CBU stability studies and segment evaluation

Cryopreservation volume/bag, storage time

CBU selection for unrelated transplantation:

considerations

Variable (N) N (%) < 75% CD34+ Viability Univariate p value Multivariate p value

FACT accreditation at unit collection

Yes (n = 259) 8 (3%)

< 0.001 < 0.001

No (n = 143) 25 (18%)

Year of cryopreservation

1997 – 2004 (n = 119) 17 (14%)

0.008 NS

2005 – 2012 (n = 283) 16 (6%)

Cryo. volume (ml)

< 24.0 (n = 10) 3 (30%)

< 0.001 0.001

24.0 – 26.0 (n = 302) 10 (3%)

26.1 – 30.0 (n = 35) 5 (14%)

> 30.0 (n = 55) 15 (27%)

Processing method

Manual (n = 188) 24 (13%)

0.002 0.010

Automated +

semi-automated (n = 214) 9 (7%)

 Method for CBU preparation for infusion: wash or albumin dilution – final volume validated method

 Post-thaw evaluation studies

National Cord Blood Program:

Collections - Rodica Ciubotariu, MD, PhD Quality Control - Susana Albano, PhD

IT Systems - Michal Tarnawski, MD Manufacturing - Ludy Dobrila, PhD

Medical Director - Andromachi Scaradavou, MD Program Director - Pablo Rubinstein, MD