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PL © Prateek Lala, SA4L, 2014 Stem Cell Transplant: Why Your Donation Matters Prateek Lala, MD June 2014 Prateek Lala, MD June 2014 South Asians for Life www.SA4L.org
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 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 CCS, 2010
PL © Prateek Lala, SA4L, 2014 Leukemia treatment Treatment for leukemia is individualized for each patient and may include one or more of: Chemotherapy Radiation therapy Stem cell transplantation
PL © Prateek Lala, SA4L, 2014 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)
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 Stem cell transplant 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 A B C DR DQ DP
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 Matching in populations Ethnic minorities are under-represented in stem cell registries Patients from these ethnic groups are much less likely to find suitable donors Data from U.S. National Cancer Institute Japanese99% African American 50% African American 50% N. American Caucasian 93% Asian 50% Asian 50%
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 Canadian registry However, of all registered donors, many ethnic minorities are significantly underrepresented: * “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 71.5% 11.2% 4.8% 4.4% 2.8% 1.8% 1.1% 1.0% 0.9% 0.8% Data: OneMatch, December 2013
PL © Prateek Lala, SA4L, 2014 OneMatch registration Online: Go to www.onematch.ca for detailed information, and instructions to registerwww.onematch.ca Phone: 1-888-2DONATE (236-6283) Either method is free for Canadian residents (must have provincial health card)
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 OneMatch registration The kit contains detailed info on how to collect a sample The process is simple, and takes 10-15 minutes to complete
PL © Prateek Lala, SA4L, 2014 Swab instructions
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 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 Unrelated Transplants to Canadian Patients
PL © Prateek Lala, SA4L, 2014 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...
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 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 *G-CSF: granulocyte colony stimulating factor (filgratim, Neupogen™)
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 Bone marrow harvest
PL © Prateek Lala, SA4L, 2014 Bone marrow harvest 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 Puncture sites
PL © Prateek Lala, SA4L, 2014 Patient transplant Harvested stem cells are filtered, and given to the patient intravenously Emru Townsend www.healemru.com
PL © Prateek Lala, SA4L, 2014 Transplant vs. chemotherapy In leukemia patients, stem cell transplant increases the long-term survival rate by 2-3 times over chemotherapy alone: http://www.meds.com/leukemia/current/curr4.html Therapy (AML patients)Success rate 14 prospective studies (1984-1994) Unrelated donor transplant40-64% Chemotherapy19-24% Recent prospective study Unrelated donor transplant54% Chemotherapy30%
PL © Prateek Lala, SA4L, 2014 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)
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 Other ways to help Consider: Blood and blood product donation Monetary donations 1-888-2DONATE (236-6283) www.blood.ca
PL © Prateek Lala, SA4L, 2014 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: email@example.com firstname.lastname@example.org
PL © Prateek Lala, SA4L, 2014 Resource slides
PL © Prateek Lala, SA4L, 2014 Blood cell development
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 HLA in families 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 a a b b c c d d d d d d c c c c a a a a b b b b motherfather child 4child 3child 2child 1
PL © Prateek Lala, SA4L, 2014 HLA markers 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 A B C DR DQ DP A1 A2 A3 A4 A5 … A527 *Fortunately, these genes are not independently assorted, making the odds much more manageable.
PL © Prateek Lala, SA4L, 2014 Important HLA markers Data adapted from U.S. National Cancer Institute and IMGT/HLA Database 5 most important HLA markers for stem cell match, used in donor search No. of possible alleles at locus Varieties of HLA genes DPβDQβDRβ 68 114 16 25 2 546 DPαDQαDRα 283 527 911 BCA 1000 800 600 400 200 0 DRB1 B A C DQB1 If a potential donor matches at all 5 pairs of loci, this is a near- perfect “10/10” match 527 × 911 × 283 × 546 × 68 = 5 trillion independent combinations
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 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
PL © Prateek Lala, SA4L, 2014 Bone marrow harvest Source: Wikipedia (http://en.wikipedia.org/wiki/Bone_marrow_transplant)
PL © Prateek Lala, SA4L, 2014 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)
PL © Prateek Lala, SA4L, 2014 Cord blood donation –196°C stem cell purification, expansion cryogenic preservation (freezing) stem cell transfusion match found, stem cells thawed
PL © Prateek Lala, SA4L, 2014 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)http://www.cellsforlife.com/victoriaangel Héma-Québec, at certain Montréal hospitals (www.hema-quebec.qc.ca)www.hema-quebec.qc.ca Alberta Cord Blood Bank (www.acbb.ca)www.acbb.ca
PL © Prateek Lala, SA4L, 2014 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 www.bethematch.org
PL © Prateek Lala, SA4L, 2014 Indian registries Three small registries currently participate* Bharat Stem Cells 209 C, 2nd floor Masjid Moth South Extension Part-2 110049 New Delhi, India Tel: +91-97172-22451 Tel: +91-98991-31630 Email: email@example.com 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: firstname.lastname@example.org Website: http://www.datriworld.orghttp://www.datriworld.org Marrow Donor Registry India Raheja/Fortis Hospital, Old Wing Miham, Raheja Rugnalaya Marg 400016 Mumbai, India Tel: +91-22-6515-2695 Tel: +91-922-35-86076 Email: email@example.com Website: http://www.mdrindia.orghttp://www.mdrindia.org *No other South Asian registries currently exist.
PL © Prateek Lala, SA4L, 2014 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 *Data (from BMDW website) as of June 1, 2014
PL © Prateek Lala, SA4L, 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
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