Donor Screening Challenges for Cord Blood Products

Creating Connections. Saving Lives.™

NATIONAL MARROW DONOR PROGRAM®

Donor Screening Challenges for Cord Blood Products

John P. Miller, MD PhD

Senior Medical Director, NMDP

7th Annual Somatic Cell Therapy Symposium

September 26, 2007

Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®

2 3/2006

What We Will Cover Today

§ How are cord blood donors different from other tissue, blood and adult HSC donors

§ What are some of the challenges and issues for donors and cord blood banks during the donation process:– Recruitment– Consent– Collection– HHQ and medical evaluation– IDM and other blood samples – Eligibility Determination– Post-donation information– Post-donation process changes impacting previously banked

units


3 3/2006

Overview: Cord BloodCollection

§ Recruitment– Pre-conception through early stages of labor

– Education through OB offices and clinics

§ Consent for donation and banking– Initial consent may occur at recruitment

through early stages of labor

– Many banks reaffirm consent at time of delivery

– Consent for collection vs consent for banking

– Includes consent for maternal IDM testing


4 3/2006

Overview: Cord Blood Collection§ Collection

– In utero vs ex utero– Remote sites– Goal is maximal # of HSCs (TNC, CD

34+, CFU)

§ HHQ and medical evaluation– Infectious disease transmission– Transmissible genetic disease– Microbial contamination

§ IDM and hemoglobinopathy testing– Exclude compound heterozygotes and

disease

§ Cryopreservation and storage: local vs distant processing


5 3/2006

Cord Blood Donors: Differences

§ Recruitment: – Most mothers wish to donate when aware of possibility– Not all will be able to do so

§ HHQ is maternal, not the infant donor– Donor has not lived long enough to manifest all transmissible genetic

disease

§ H & P is maternal and infant§ IDM testing is performed on maternal samples§ Unlike HSC products from adult donors, cord blood is banked§ Research (IRB/IND) or BLA§ There is significant attrition of recruited donors…


6 3/2006

ARC Cord Blood Bank, St. Paul10/1999 to 10/2001

Relative AmountNStage

0.00412CBU Transplanted

0.02166CBU Quarantined

0.401255CBU Banked

1228CBU Discarded

0.822561CBU Collected

0.852666Placenta Received

1.03130Mothers Consented

1.163636Mothers Approached


7 3/2006

Cord Blood Collection Challenges

§ Physiological

§ Logistical


8 3/2006

Physiological Challenges

§ Small placenta

§ Low blood volume collection– training & experience can improve volume

– “mother nature” plays big role

§ Low cellular content

§ Delivery complications– Damaged cord from delivery

– Placental tears


9 3/2006

Logistical Challenges

§ Most controllable cord blood collection challenges are logistical issues

§ Cord Blood Banks can design their procedures to impact these factors

§ However, there are trade-offs when these choices are made

§ Let’s go through some examples at each stage of the donation process…


10 3/2006

Recruitment

§ Key challenge for banks and goal of legislation and funding: increase minority recruitment

§ Want diverse HLA haplotypes in donor pool

§ Banks may face cultural issues, e.g.,– Role of the family in the decision to donate

– Body Integrity and sample draws

– Placental significance


11 3/2006

Recruitment

§ Recruitment may happen any time before conception through early stages of labor

§ Media and private banks have brought attention to cord blood donation

§ However, we do not want to “over recruit”and disappoint mothers who will not have access to donation

§ Need to exclude “high risk” deliveries


12 3/2006

Consent

§ Mom acts a surrogate for her child

§ Age of consent is usually 18

§ What about emancipated minors?

§ If clinical care is needed, mother consents


13 3/2006

Collection

§ In utero vs. ex utero

– GMP issues, e.g. training, etc.

– Cost

§ Remote collections

– May be especially important for directed donations and for minority collections


14 3/2006

Health History

§ When to get health history information:– Registration

– Delivery

– After Delivery

– After Discharge

§ How do we assure privacy and therefore truthful answers?

§ Paternal Health History is of little value


15 3/2006

Health History: Specific questions

§ Parent(s) adopted

§ Egg/sperm donor

§ Multiple miscarriages

§ First cousins

§ First degree relatives (parents, siblings) with malignant or nonmalignant hematologic disorders


16 3/2006

Medical Evaluation and Delivery

§ Who should obtain maternal and neonatal health information?

– Trained CBB staff

– Hospital staff

§ When should information be obtained?


17 3/2006

IDM and other testing

§ When to obtain maternal samples?

§ Hemoglobinopathy screening: state vsindependent testing


18 3/2006

Eligibility Determination

§ How soon should this be done?

§ All HHQ, medical evaluation and testing must be available; tracking down all the information may take time

§ AABB and FACT requirements


19 3/2006

Post-Donation Information

§ Consent often limits conditions for re-contacting the mother

§ Mother/family may be unable to be located

§ How to handle new information for previous donations?


20 3/2006

Post-Donation Process Changes Potentially Impacting Banked Units

§ Do older units get “grandfathered”, or

§ Do these units get de-listed, or…

§ Can we do further evaluation or labeling at the time of confirmatory typing?– e.g. Pooled vs single donor NAT

– e.g. Chagas Disease?

§ Sample storage requirements may limit the options


21 3/2006

Competitive

§ Other research projects

§ Private Banking


22 3/2006

FDA Donor Eligibility and Licensure


23 3/2006

Regulatory Issues in Unrelated Cord Blood Banking

§ Existing products (prior to licensure, aka “retro”units) need to be available for transplantation

§ Indications for cord blood transplantation should be broadened to include non-malignant conditions

§ Importation of cord blood units (CBUs) is essential to meet the needs of US transplant patients; the regulatory framework needs to allow continued importation of these products


24 3/2006

Current Question: Should We Test for Chagas?

§ Not a relevant communicable disease

§ It is transmitted by blood (HCT/Ps)

§ Licensed test is available

§ Unclear if trypanosome survives cryopreservation

§ Brian Custer will discuss this later in his session on decision analysis


25 3/2006

Summary

§ Most controllable cord blood donation issues are logistical

§ Cord blood banks make choices when designing their procedures

§ No model is perfect, careful decisions and trade-offs are made.


26 3/2006

Thank you

§ Any questions?


27 3/2006

Extra Slides for possible discussion follow…..


28 3/2006

Older CBUs: Today vs Unlicensed Units in the Post-licensure Era

§ Represent a large proportion of the current inventory and units used for transplantation

§ Given the size of the inventory and need for high degrees of HLA matching, these units will continue to be needed even with increased collection and banking of CBUs

§ Documentation of retrospective,“equivalent GMP”will be difficult or not possible for cord banks; may these units be distributed under a “perpetual” IND?

§ NMDP data indicates that older units have similar clinical outcomes (survival and engraftment)


29 3/2006

CBU Inventory by Collection Date

CBUs collectedbefore 5/25/05

CBUs collected onor after 5/25/05

Total InventoryN=62,021

CBUs collectedbefore 5/25/05CBUs collected onor after 5/25/05

Shipped CBUsN=1,383

80% collected before 5/25/05

Before 5/25/05

92% of CBUs for transplant

Before 5/25/05


30 3/2006

Survival after Primary Cord Blood Transplants(February 2000 – December 2005)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1 2 3

Years After Transplant

Sur

viva

l

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

From 5/25/2005 (n = 69)

Before 5/25/2005 (n = 267)

Log-rank p-value = 0.70


31 3/2006

Transplantation for Non-malignant disorders

§ Transplants of CBUs for non-malignant disorders represent 27% of total transplants from Feb 2000 to Dec 2005

§ Are these units available for “off label” use by transplant physicians, and if so…

§ Is the cord blood bank responsible for how the TC MD uses the product after it is shipped?

§ As the indications for specific non-malignant disorders are rare, how would we move from IND to licensure?

§ NMDP data suggests similar outcomes (engraftment and survival) for transplants for malignant and non-malignant hematologic disorders


32 3/2006

Survival after Primary Cord Blood Transplants(February 2000 – December 2005)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1 2 3

Years After Transplant

Sur

viva

l

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Hematologic malignancies (n = 245)

Non-malignant diseases (n = 89)

Log-rank p-value = 0.13


33 3/2006

Importation of CBU

§ Imported CBUs are needed to meet the needs of US patients for HLA matched units, current domestic CBU inventory is not adequate

§ Imported CBUs represent a significant proportion of the units for transplantation, but many international banks only ship a few units and may not apply for licensure

§ Are CBUs importable under a “perpetual” IND or other mechanisms?


34 3/2006

Importation of CBUs: CY 2006

U.S. Total NMDP

19% 14%

Domestic Domestic

Import Import

N = 891 N = 468

Documents

Donor Screening Challenges for Cord Blood Products