Not All Stem Cells are the Same

Jennifer Willert, M.D.

Hematology/Oncology

Blood and Marrow Transplant

Rady Children’s Hospital San Diego

Clinical Professor UCSD

Cord Blood Banking and Transplantation

Not All Stem Cells are the Same

Embryonic Stem Cells Embryonic Stem Cells

Newborn Stem Cells Newborn Stem Cells

ƒCord Blood

Adult Stem Cells Adult Stem Cells ƒBone Marrow ƒPeripheral Blood ƒLimited supply ƒEthical issues ƒNo clinical data ƒBiological constraints Advantages Limitations

ƒYounger, excellent proliferation and differentiation abilities

ƒImmediately available

ƒLess stringent HLA requirements

ƒLower risk of GvHD, infections

ƒAutologous transplants possible

ƒHigh developmental potential

ƒHigh proliferative capacity

ƒLittle risk of viral contamination

ƒAbility to differentiate

ƒRich concentration of stem cells

ƒGreatest amount of historical data

ƒRapid engraftment

ƒGood historical data

ƒLess invasive than bone marrow

ƒFacilitates easier autologous transplants

ƒDelayed short-term engraftment

ƒOne-time supply

ƒComplex harvest

ƒMinimal residual disease (MRD)

ƒIncreased potential for GvHD

Cord Blood Stem Cell Timeline

Adapted from: Emerging stem cell therapies. Supplement to OBG Management. 2006.

1978 1988 1992 1993 1997 2005 2008

Cord blood proposed as source of stem cells

First family cord blood stem cell bank (for use by related individual)

NEJM study

demonstrated higher survival rates with related cord blood cell transplants than

with unrelated

More than 10,000 transplants have been performed

to date

First cord blood stem cell transplant from a related donor for Fanconi's anemia First successful transplantation from an unrelated donor Stem Cell Therapeutic and Research Act

0 2000 4000 6000 8000 10000 1994 1995 1996 1997 1999 2000 2001 2002 2003 2004 2005 2006 2007

Cord Blood Stem Cell (CBSC) Transplants

Cord Blood Stem Cells Are Increasingly 

Being Used to Save Lives

Cord Blood Banking Options: 

Private and Public

Public Cord Blood Banking:

Unrelated

Donor Banks

ƒ 48%–66% of all samples collected are  banked ƒ Sample is available to any matched  recipient; not all patients will find a  match ƒ No cost for collection or storage; cost  is ~$15,000 to $35,000 to the treating  institution for sample retrieval ƒ Access denied to some due to limited  number of public banks

Private Cord Blood Banking: 

Related

Banks 

ƒ 98% of collected samples are banked ƒ Samples are reserved and available at  any time for family use ƒ Cost is ~$1500 to $2000 upon  collection plus $100 to $125 annual  storage fee ƒ Is an option accessible to anyone in  the United States

Both options help address the potential needs of patients

Diseases That Could Currently 

Benefit From CBSC Transplants

ƒ Leukemia ƒ Lymphoma ƒ Multiple Myeloma ƒ Hurler Syndrome ƒ Niemann‐Pick Disease ƒ Severe Combined  Immune Deficiency ƒ Sickle‐Cell Anemia ƒ Aplastic Anemia ƒ Fanconi Anemia ƒ Beta‐Thalassemia Malignancies Metabolic Disorders Blood Disorders

Many Emerging Therapies are Under Investigation Including Heart Disease, Diabetes, and Brain Injury

Blood and Marrow Transplant

Approximately 500 CBSC transplants occur annually in the U.S.

Bone Marrow Transplant Registry

33%

Family Match

_66%

No Family Match

Up to 75%

Find No Suitable Match

25%

Find Suitable Match

Many Patients Don’t Find a Match

Up to 50% of All PatientsNeeding Stem Cell Transplants Are Unable to Find a Match

Patients Needing Bone Marrow Transplants

Source: 1) Perlow JH. Contemp Ob/Gyn. 2002.

Advantages of CBSC Over Bone Marrow

ƒ Immediate availability

ƒ Simpler collection process

ƒ Elimination of surgical harvest

ƒ Reduction in time to treatment

ƒ Decrease in frequency of certain infections

ƒ More tolerant of HLA mismatches

ƒ Lower risk of GvHD

ƒ Provide better long‐term immune function

Outcomes of CBSC Transplants

Compared With Bone Marrow in Children

Cord Blood Stem Cell Transplantation

Provides Improved Outcomes for Patients

Equivalent

Survival 

Equivalent

Relapse 

Equivalent

Early Transplant Related Mortality  

Slightly Longer

Time to Engraftment  

Improved

Chronic GvHD  

Improved

Acute GvHD  

Cord Blood

Outcome

Advantages of Related CBSC

ƒ Genetically unique to child or sibling

ƒ Increased chance of intra‐familial matching

ƒ Known family history

ƒ Decreased morbidity/mortality

ƒ Readily available/accessible

Source: 1) Gluckman E, et al. NEJM 1997.

63% 29% Related CBSC Transplants Unrelated CBSC Transplants

CBSC Transplants Are Highly Successful,

Particularly in Related Stem Cell Transplants

•Provide best clinical outcomes ƒ Less GvHD ƒ Improved survival

•Genetically unique

•Known family history

•Immediately available/accessible 

•Expected lower costs 

ƒ No sample procurement ƒ Less acute GvHD treatment ƒ Fewer chronic GvHD medication  requirements Sources: 1. Gluckman E et al. N Engl J Med. 1997.  2. Wagner J et al. Lancet. 1995. 1 N=78 N=44 Higher Clinical Success Rates With  Related CBSC Transplants²

One‐Year Survival

1 85% 72% 3% Engraftment Survival GvHD

Brandyn

•14‐year‐old male •Diagnosed with leukemia as a toddler •Years of chemotherapy led to remission,  until relapse and need for stem cell  transplant •Blood from younger siblings’ umbilical  cord and placenta was banked at birth ƒ Stored at a private bank, alleviating the need to find a match from donor hospital  or public registry  ƒ Blood was rich in stem cells •November 2, 1999 Brandon received his  cord blood transplant and continues to do  well.

“It was enough to do the transplant. It was the most wonderful news I’ve

ever heard.” — Brandyn’s Mother

Titus

•Diagnosed at 18 months with aplastic anemia ƒ He was unable to produce any red blood cells on his own •Titus’s mother became pregnant again; the hospital recommended that the family store  the cord blood stem cells with Cord Blood  Registry ƒ The baby’s cord blood was collected at no cost, as part of CBR’s Designated Transplant Program ƒ Stem cells were found to be a perfect match •December 30, 2004,Titus received his cord  blood transplant and is doing well

“As a mother, you’ll do anything to help you son. I’m really glad the hospital recommended Cord Blood

Registry.”

— Titus’s Mother

Joseph Jr.

“It was about 20 days after the transplant when all of a sudden he started feeling better.” — Joseph’s Father •6‐year‐old male •Diagnosed at birth with sickle cell anemia ƒ Joseph required frequent blood transfusions  •Joseph’s mother became pregnant with a  second child ƒ Amniocentesis revealed that the baby was a  perfect match for Joseph Jr. ƒ Joseph’s younger brother’s umbilical cord blood  was banked at birth free‐of‐charge as part of  CBR’s Designated Transplant Program  •The transplanted stem cells created new blood  and a new immune system  •More than five years after the transplant,  Joseph is healthy and vibrant

Designated Transplant Program

ƒ Established in 1996 to increase accessibility 

of stem cell transplantation to patients in need

ƒ Eligibility criteria

•Affected family member is first‐ or second‐degree  relative of newborn •Treating transplant physician confirms that affected  family member is in need of a stem  cell transplant

ƒ All expenses of collection, processing, and storage are 

waived for DTP clients

ƒ Through the DTP, CBR has stored cells for over 2000 

families

Empower Patients to Make an 

Informed Choice for the Future

Who

should receive

information about

cord blood banking?

ƒ All expectant parents 

ƒ Family history of genetic disorders may pose particular 

need for education about cord blood banking

Preparing for a Healthy Birth and Life

• Oral Glucose Challenge Test (28 weeks) • Maternal Serum Screen • Ultrasound (15–20 weeks) • BPP • Non Stress Test

(Post week 30)

• Initial hGC pregnancy test • Prenatal Blood screening • Rh incompatibility test

& urinalysis

• CVS

• Nuchal Translucency Sono

(Initial visit-14 weeks)

• CBSC banking discussed if multiple ethnicity exists (Initial visit) • Introduce CBSC banking options (20 weeks) • Amniocentesis (Post week 16)

Throughout Pregnancy Numerous Tests Are Conducted to Ensure the Present and Future Health of Mother and Baby

Weeks

6

12

18

24

30

36

42

• PUBS (18–36 weeks) • Cord Blood Collection (At delivery)

National and State Public Policy Continue to 

Drive Stem Cell Education and Awareness

In addition to an Institute of Medicine (IOM) report and federal legislation centered on the  creation of a national public bank, Cord Blood legislation has passed in 20 states.

Odds of Use

Autologous

1 in 400 chance of being a SC transplant recipient

Autologous/Allogeneic

1 in 200 chance of being a SC transplant candidate

Odds Of Usage Over 70-year Span

Based Solely On Current Indications

1

_*:

Source: 1) Pasquini MC, et al. Blood. 2005.

Does Not Include Emerging, Potential Uses of Cord Blood Stem Cells to Treat Heart Disease, Diabetes, Parkinson’s, Stroke,

Muscular Dystrophy, and Spinal Cord Injury

Factors Patients Need to Consider 

When Assessing a Cord Blood Bank

ƒ Experience

• How many medical centers have utilized cells in transplant that were  processed and stored with the cord blood bank?  How recently? • How many clients have samples stored at their facility? • What is the longest time a unit has been stored and then used in a  transplant?

ƒ Cell recovery

• What percentage of cells do they recover from their processing?

ƒ Publication of results

• Have they published data to support their processing and storage methods?

ƒ Financial stability

• How long has the company been in operation and are they likely to be  around in the future?

ƒ Location of facility

• Are there risks associated with the location of the storage facility   (tornadoes, hurricanes, airport closures, etc)?

ƒ Clinical studies over the past 20 years demonstrate the 

efficacy and safety of cord blood stem cells

ƒ Cord blood stem cells can be easily collected and stored

ƒ Cord blood stem cells are clinically useful in a variety of 

disease states and demonstrate tremendous future potential

ƒ All expectant families should receive information about their 

options for collecting and storing their child’s cord blood stem 

cells

ƒ OBs play a vital role in ensuring families receive accurate 

information

Cord Blood Stem Cells