Donor Screening Challenges for Cord Blood Products
Transcript of 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
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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
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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
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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
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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…
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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
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Cord Blood Collection Challenges
§ Physiological
§ Logistical
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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
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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…
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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
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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
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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
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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
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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
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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
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Medical Evaluation and Delivery
§ Who should obtain maternal and neonatal health information?
– Trained CBB staff
– Hospital staff
§ When should information be obtained?
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IDM and other testing
§ When to obtain maternal samples?
§ Hemoglobinopathy screening: state vsindependent testing
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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
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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?
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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
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Competitive
§ Other research projects
§ Private Banking
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FDA Donor Eligibility and Licensure
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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
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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
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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.
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Thank you
§ Any questions?
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Extra Slides for possible discussion follow…..
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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)
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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
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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
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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
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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
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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
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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?