Stem Cell Transplant: Why Your Donation Matters

1. South Asians for Life www.SA4L.org Stem Cell Transplant:Why Your Donation Matters Prateek Lala, MD June 2014

2. 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

3. Leukemia types • Acute leukemias progress more rapidly, and must be treated more urgently CCS, 2010 • 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)

4. Leukemia treatment • Treatment for leukemia is individualized for each patient and may include one or more of: • Chemotherapy • Radiation therapy • Stem cell transplantation

5. 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)

6. 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

7. B Stem cell transplant A C DR DP DQ 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

8. 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

9. Matching in populations N. American Caucasian 93% Japanese 99% African American 50% Asian 50% 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

10. 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

11. Canadian registry • However, of all registered donors, many ethnic minorities are significantly underrepresented: 71.5% 11.2% 4.8% 4.4% 2.8% 1.8% 1.1% 1.0% 0.9% 0.8% Data: OneMatch, December 2013 * “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

12. 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)

13. 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

14. 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

15. OneMatch registration The kit contains detailed info on how to collect a sample The process is simple, and takes 10-15 minutes to complete

16. Swab instructions

17. 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

18. OneMatch registration Unrelated Donations from Canadian Donors Unrelated Transplants to Canadian Patients 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

19. 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...

20. 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

21. 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

22. 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™)

23. PBSC collection Read Steven McEvoy’sdetailed description of his donor experience at: http://www.bookreviewsandmore.ca/2007/06/there-more-than-blood-in-you-to-give.html

24. 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

25. Bone marrow harvest

26. 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

27. Patient transplant Emru Townsend www.healemru.com Harvested stem cells are filtered, and given to the patient intravenously

28. Transplant vs. chemotherapy http://www.meds.com/leukemia/current/curr4.html In leukemia patients, stem cell transplant increases the long-term survival rate by 2-3 times over chemotherapy alone:

29. 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)

30. 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

31. Other ways to help • Consider: • Blood and blood product donation • Monetary donations • 1-888-2DONATE (236-6283) • www.blood.ca

32. 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

33. Resource slides

34. Blood cell development

35. What is HLA? • These HLA markers prevent our immune systems from attacking our own cells 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)* *HLA is different fromthe simpler “ABO-Rh” markers that define blood types

36. HLA in families c d a b 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

37. HLA markers B A1 A2 A3 A4 A5 A C … A527 DR DP DQ • There are sixmajor 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 *Fortunately, these genes are not independently assorted, making the odds much more manageable.

38. 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 near- perfect “10/10” match DRB1 DQB1 1000 800 600 400 200 0 Varieties of HLA genes 911 546 No. of possible alleles at locus 527 283 114 68 25 16 2 A B C DRα DRβ DQα DQβ DPα DPβ 527 × 911 × 283 × 546 × 68 = 5 trillion independent combinations Data adapted from U.S. National Cancer Institute and IMGT/HLA Database

39. 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

40. 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

41. Bone marrow harvest Source: Wikipedia (http://en.wikipedia.org/wiki/Bone_marrow_transplant)

42. 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)

43. Cord blood donation stem cell purification, expansion cryogenic preservation (freezing) match found, stem cells thawed stem cell transfusion –196°C

44. 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)

45. 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

46. Indian registries 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: bharatstemcellregistry@gmail.com Marrow Donor Registry India Raheja/Fortis Hospital, Old Wing Miham, RahejaRugnalayaMarg 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 Three small registries currently participate* *No other South Asian registries currently exist.

47. 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

48. 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