Download Stem Cell Transplant

South Asians for Life
www.SA4L.org
Stem Cell Transplant:
Why Your Donation
Matters
Prateek Lala, MD
June 2014
© Prateek Lala, SA4L, 2014
PL
What is leukemia?
• Leukemia is a malignant cancer affecting
the bone marrow and blood
• All leukemias develop from a stem cell in the
bone marrow that grows and multiplies
uncontrollably
• Leukemia cells eventually crowd out normal
bone marrow cells, causing problems with
normal blood cell production
© Prateek Lala, SA4L, 2014
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Leukemia types
• The four most common types of leukemia in
adults are:
•
•
•
•
acute myelogenous leukemia (AML)
acute lymphocytic leukemia (ALL)
chronic myelogenous leukemia (CML)
chronic lymphocytic leukemia (CLL)
• Acute leukemias progress
more rapidly, and must
be treated more urgently
© Prateek Lala, SA4L, 2014
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CCS, 2010
Leukemia treatment
• Treatment for leukemia is individualized
for each patient and may include one or
more of:
• Chemotherapy
• Radiation therapy
• Stem cell transplantation
© Prateek Lala, SA4L, 2014
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What are stem cells?
• Stem cells are cells that can mature and
develop into many other kinds of cells
• Stem cells in the bone marrow generate
all types of blood cells:
• Red blood cells (carry oxygen)
• White blood cells (immunity)
• Platelets (help clotting)
© Prateek Lala, SA4L, 2014
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What are stem cells?
• These are not embryonic stem cells (no
fetuses are involved)
• Stem cells used for transplant to cure
cancers and other diseases are taken
from the blood (or bone marrow) of
consenting adult donors
• This technology has been in use for the last
40 years
© Prateek Lala, SA4L, 2014
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Stem cell transplant
A
B
C
DR
DP
• In order to perform a stem cell
transplant, a suitable source of stem
cells must be found
• This means finding a donor whose stem
cells are similar to (“match”) the
patient’s cells
• “Matching” means having the same (or
very similar) pattern of HLA markers
DQ
© Prateek Lala, SA4L, 2014
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HLA in populations
• Patients are more likely to find a match
within their own ethnic communities
• HLA patterns tend to be more similar
within ethnic groups
• National and international registries of
HLA markers (stem cell registries) are
searched to find matches for the 70% of
patients who have no family match
© Prateek Lala, SA4L, 2014
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Matching in populations
African
American
50%
N. American
Caucasian
93%
Asian
50%
Japanese
99%
Data from U.S. National Cancer Institute
• Ethnic minorities are under-represented in
stem cell registries
• Patients from these ethnic groups are much
less likely to find suitable donors
© Prateek Lala, SA4L, 2014
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Canadian registry
• OneMatch Stem Cell and Marrow
Network, managed by Canadian Blood
Services
• As of December 2013, 329 285 people
are registered in Canada
• www.onematch.ca
© Prateek Lala, SA4L, 2014
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Canadian registry
• However, of all registered donors, many ethnic
minorities are significantly underrepresented:
Data: OneMatch,
December 2013
Caucasian
71.5%
East/SE Asian
11.2%
South Asian
4.8%
Other
4.4%
Unknown
2.8%
Multi-ethnic
1.8%
Aboriginal
1.1%
Black
1.0%
Arab/West Asian
0.9%
Latin/Hispanic
0.8%
* “East/SE Asian” includes donors self-identified as: Asian, Chinese, Filipino, Japanese, Korean, and Southeast Asian
** “South Asian” includes donors self-identified as: East Indian and South Asian
© Prateek Lala, SA4L, 2014
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OneMatch registration
• Online:
• Go to www.onematch.ca for detailed
information, and instructions to register
• Phone:
• 1-888-2DONATE (236-6283)
• Either method is free for
Canadian residents (must
have provincial health card)
© Prateek Lala, SA4L, 2014
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OneMatch registration
• Donors in Canada must be:
• Between 17-35 years of age*
• In generally good health
• Committed to donating to any patient
• Those who join the registry do so for
all patients in need, not just one
*Current recruitment focus on ethnic males: research indicates that younger, male
donors provide better patient outcomes
© Prateek Lala, SA4L, 2014
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OneMatch registration
• Registering online: you will be contacted
by phone for follow-up questions and to
confirm interest
• In a few days, you will receive a cheek
swab kit by mail
• Swabs are used to collect cell samples
from the inside of your cheek, for DNA
analysis of your HLA markers
© Prateek Lala, SA4L, 2014
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OneMatch registration
• The kit contains detailed info on how to
collect a sample
• The process is simple, and takes 10-15
minutes to complete
© Prateek Lala, SA4L, 2014
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Swab instructions
© Prateek Lala, SA4L, 2014
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OneMatch registration
• Once your sample is received by
OneMatch, it is analyzed and results are
entered into the database, usually in
about 3-4 weeks
• Please keep OneMatch notified of
changes in your contact info, so they can
reach you if you are found to be a match
© Prateek Lala, SA4L, 2014
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OneMatch registration
• If you are found to match with a patient in
need, only then will OneMatch contact you
• Donation could be for Canadian or
international patients
Unrelated Donations from Canadian Donors
© Prateek Lala, SA4L, 2014
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Unrelated Transplants to Canadian Patients
Blood stem cell therapy
• Stem cell transplant can help cure many
diseases, such as:
• Cancers: leukemia, lymphoma, myeloma...
• Bone marrow diseases: sickle cell anemia,
thalassemias, aplastic anemia...
• Immune system disorders: severe combined
immunodeficiency, Wiskott-Aldrich syndrome…
• Genetic/metabolic diseases: metachromatic
leukodystrophy, adrenoleukodystrophy...
© Prateek Lala, SA4L, 2014
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Donation procedures
• There are two major sources of stem cells
from donors:
• Peripheral blood stem cell (PBSC)
• Bone marrow
• PBSC collection, a non-surgical technique, is
now the most commonly used method
• Presently, PBSC is used in about 85% of stem cell
collections in Canada
• Recovery time is a few hours
© Prateek Lala, SA4L, 2014
PL
Donation procedures
• The transplant physician will decide
which collection strategy to use
• Donors have the right to accept or refuse
to donate, but...
• …should consider what they are prepared
to give even before registering
© Prateek Lala, SA4L, 2014
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PBSC collection
• The donor receives 4-5 days of G-CSF*
• This growth factor increases the number of
stem cells circulating in the bloodstream
• Possible side effects include:
• Mild bone pain, fever and/or chills
• Nausea and/or vomiting
• Local irritation at injection site
• These go away 2-3 days after stopping
injections
© Prateek Lala, SA4L, 2014
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*G-CSF: granulocyte colony stimulating factor (filgratim, Neupogen™)
PBSC collection
Read Steven McEvoy’s detailed description of his donor experience at:
http://www.bookreviewsandmore.ca/2007/06/there-more-than-blood-in-you-to-give.html
© Prateek Lala, SA4L, 2014
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Bone marrow harvest
• For bone marrow donation, the donor is
given a general or regional anaesthetic
• A needle is inserted into the back of the
hip bone (not into the spine), and liquid
marrow is extracted
• Bone marrow replenishes itself within
4-6 weeks
© Prateek Lala, SA4L, 2014
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Bone marrow harvest
© Prateek Lala, SA4L, 2014
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Bone marrow harvest
Puncture sites
© Prateek Lala, SA4L, 2014
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• The most common side
effect is pain in the hip
bones at the site(s) of
collection
• However, this pain is
easily managed, and
usually lasts a few days
• Donors are usually
home the same day
Patient transplant
• Harvested stem cells are filtered, and given to
the patient intravenously
Emru Townsend
www.healemru.com
© Prateek Lala, SA4L, 2014
PL
Transplant vs. chemotherapy
• In leukemia patients, stem cell transplant
increases the long-term survival rate by
2-3 times over chemotherapy alone:
Therapy (AML patients)
Success rate
14 prospective studies (1984-1994)
Unrelated donor transplant
40-64%
Chemotherapy
19-24%
Recent prospective study
Unrelated donor transplant
54%
Chemotherapy
30%
http://www.meds.com/leukemia/current/curr4.html
© Prateek Lala, SA4L, 2014
PL
Confidential & anonymous
• All personal information provided to
OneMatch is kept confidential
• If asked to donate stem cells, the donor’s
and recipient’s identities are kept
anonymous throughout the process
• Up to the point of actual donation, donors
may withdraw at any time (though the
patient will need to find a new donor)
© Prateek Lala, SA4L, 2014
PL
Confidential & anonymous
• For one year after donation, the donor is “on hold”
and cannot donate to anyone else, in case the first
recipient requires a second transplant
• Three months after transplant, the donor can find
out how the patient has responded to transplant
• Six months after transplant, the donor and recipient
can exchange anonymous letters
• One year after transplant, if both parties wish it,
OneMatch can make arrangements for donor and
recipient to meet
© Prateek Lala, SA4L, 2014
PL
Other ways to help
• Consider:
• Blood and blood product donation
• Monetary donations
• 1-888-2DONATE (236-6283)
• www.blood.ca
© Prateek Lala, SA4L, 2014
PL
SA4L: Who we are
• Formed in 2008, South Asians for Life is a
OneMatch community partner, dedicated to
increasing awareness of and participation in
the Canadian stem cell registry
• Through our efforts, several thousand new
potential donors have been added to the
registry
• Contact us for more information:
prateek.lala@gmail.com
© Prateek Lala, SA4L, 2014
PL
Resource slides
© Prateek Lala, SA4L, 2014
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Blood cell development
© Prateek Lala, SA4L, 2014
PL
What is HLA?
• All cells in our body have markers on their surface
that identify them as belonging to itself (“self”)
• On white blood cells, these are called “human
leukocyte antigens” (HLA)*
• These HLA markers prevent our
immune systems from attacking
our own cells
*HLA is different from the simpler “ABO-Rh” markers that define blood types
© Prateek Lala, SA4L, 2014
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HLA in families
a b
c d
father
mother
a c
a d
b c
b d
child 1
child 2
child 3
child 4
• We inherit half our HLA markers from each parent (we
share only 50% of markers with each parent)
• Each full sibling has a 25% chance of matching another
(identical twins are 100% match)
• Only ~30% of patients find a family match; 70%
depend on unrelated matched donors
© Prateek Lala, SA4L, 2014
PL
HLA markers
A
B
C
…
A1
A2
A3
A4
A5
A527
DR
DP
DQ
• There are six major types of HLA markers, inherited
in pairs (along with many minor types)
• Each type can have hundreds of variants, thus
trillions of potential combinations of all 6 pairs*
• This is why it can be very difficult to find a matched
donor for a given patient
© Prateek Lala, SA4L, 2014
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*Fortunately, these genes are not independently assorted, making the odds much more manageable.
Important HLA markers
B
A
C
5 most important
HLA markers for
stem cell match,
used in donor search
If a potential donor
matches at all 5 pairs
of loci, this is a nearperfect “10/10” match
DRB1
DQB1
No. of possible alleles
at locus
1000
911
800
Varieties of HLA genes
600
400
546
527
283
200
0
2
A
B
C
DRα
DRβ
25
68
DQα
DQβ
114
16
DPα
DPβ
527 × 911 × 283 × 546 × 68 = 5 trillion independent combinations
© Prateek Lala, SA4L, 2014
PL
Data adapted from U.S. National Cancer Institute and IMGT/HLA Database
PBSC collection
• The donor is
connected to an
apheresis unit
• This unit separates
stem cells out from
the blood, then
returns the rest back
to the donor
© Prateek Lala, SA4L, 2014
PL
PBSC collection
• The harvesting procedure is essentially
painless
• No general anesthesia is given, patients
are usually back home the same day
• Stem cells regenerate to normal levels
in 3-6 weeks
© Prateek Lala, SA4L, 2014
PL
Bone marrow harvest
Source: Wikipedia (http://en.wikipedia.org/wiki/Bone_marrow_transplant)
© Prateek Lala, SA4L, 2014
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Cord blood donation
• Stem cells from umbilical cord blood are
another potential source for transplant
• Parents of a new baby may decide to donate
cord blood:
• Public registries: stem cells may be given to
anybody in need (free process, helps the greater
community)
• Private registries: stem cells are saved for possible
future need of the donor ($$$, low likelihood of
personal need)
© Prateek Lala, SA4L, 2014
PL
Cord blood donation
stem cell
purification,
expansion
cryogenic
preservation
(freezing)
stem cell
transfusion
© Prateek Lala, SA4L, 2014
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match found,
stem cells
thawed
Cord blood donation
• OneMatch has begun to offer cord blood
donation services in 2014 (pilot)
• In Canada, three public registries are
available at this time:
• Victoria Angel registry, available in S. Ontario
(http://www.cellsforlife.com/victoriaangel)
• Héma-Québec, at certain Montréal hospitals
(www.hema-quebec.qc.ca)
• Alberta Cord Blood Bank (www.acbb.ca)
© Prateek Lala, SA4L, 2014
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U.S. registries
• Largest is the National Marrow Donor Program
• As of 2012, over 9.6 million registered donors and
cord blood units
•
•
•
•
•
970 000 (10%) are Hispanic/Latino
697 000 (7%) are Black
682 000 (7%) are Asian
106 000 (1%) are Native American
355 000 (4%) are of mixed ethnicity
• Minorities can join for free
• www.bethematch.org, 1-800-MARROW2
© Prateek Lala, SA4L, 2014
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Indian registries
• Three small registries currently participate*
Bharat Stem Cells
Marrow Donor Registry India
209 C, 2nd floor
Masjid Moth
South Extension Part-2
110049 New Delhi, India
Tel: +91-97172-22451
Tel: +91-98991-31630
Email: bharatstemcellregistry@gmail.com
Raheja/Fortis Hospital, Old Wing
Miham, Raheja Rugnalaya Marg
400016 Mumbai, India
Tel: +91-22-6515-2695
Tel: +91-922-35-86076
Email: info@mdrindia.org
Website: http://www.mdrindia.org
DATRI Blood Stem Cell Donors Registry
New 37, Old 20-G, 2nd Avenue
Shastri Nagar, Adayar
600 020 Chennai, India
Tel: +91-98402-18667
Email: raghu@datriworld.org
Website: http://www.datriworld.org
© Prateek Lala, SA4L, 2014
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*No other South Asian registries currently exist.
International registry
• Bone Marrow Donors Worldwide
currently has 24,051,634 stem cell
donors available*
• 73 donor registries from 52 countries, 47
cord blood banks from 32 countries
• www.bmdw.org
© Prateek Lala, SA4L, 2014
PL
*Data (from BMDW website) as of June 1, 2014
Timeline
1956: E.D. Thomas (Cooperstown, NY) performs first successful human bone marrow
transplant (BMT) between identical twins
1958: J. Dausset (Paris) identifies first of many HLA antigens
1968: R.A. Good (Minnesota) performs first successful BMT from matched, related
(non-twin) donor
1973: First successful matched, unrelated BMT performed at Sloan-Kettering Cancer
Centre (New York)
1974: Anthony Nolan Trust (UK) starts first dedicated bone marrow registry
1980: Dausset, B. Benacerraf, and G.D. Snell win Nobel for discovery of HLA
1986: National Bone Marrow Donor Registry started in USA, first donor match made in
1987
1988: E. Gluckman (Paris) successfully transplants cord-blood stem cells, for a patient
with Fanconi anemia
1989: Unrelated Bone Marrow Donor Registry started in Canada*; Bone Marrow
Donors Worldwide (BMDW) established
1990: Thomas and J.E. Murray win Nobel for work in transplant biology
1995: Bensinger et al. transplant peripheral blood stem cells to treat hematological
malignancies, demonstrate superiority to BMT
2012: BMDW records its 20 millionth registered stem cell donor worldwide
*The UBMDR came under the auspices of Canadian Blood Services in 1998, and became OneMatch in 2007
© Prateek Lala, SA4L, 2014
PL