Bone Marrow Donors Worldwide Annual Report 2011

Transcription

1 Bone Marrow Donors Worldwide Annual Report 2011

2 Bone Marrow Donors Worldwide Annual Report 2011 Contact address Bone Marrow Donors Worldwide Europdonor Foundation Plesmanlaan 1B 2333 BZ Leiden The Netherlands Tel: Fax: Acknowledgements Photographs by courtesy of Europdonor. Graphic Design: Five Spices b.v., The Hague. Leiden, 2012

3 page I Preface Jon van Rood has been the chairman of the Editorial Board of the BMDW since its beginning in He has done a tremendous job in getting all of 47 countries to participate in BMDW. There are very few organizations worldwide working with so many countries together in harmony. We thank him for what he has done for BMDW. Prof.dr. Jon van Rood and Prof.dr. Eliane Gluckman during his BMDW farewell diner in Paris, France, March 31, There are now well over 18 million donors and over 500,000 cord blood units in BMDW to search for patients worldwide. New features have been added to BMDW and many are still to follow. The most important addition has been the option to select cord blood units which are HLA mismatched but matched for the Non Inherited Maternal Antigens (NIMA). Such HLA mismatched but NIMA matched cord blood units have a prognosis similar to that of 6/6 matched cord blood units. We encourage all cord blood banks to HLA type the mothers of the cord blood units and provide the data to BMDW so more patients will benefit from NIMA matched cord blood units. Of course we also encourage the transplant centers to use the NIMA match program and to search for NIMA matched units if no 6/6 unit is available. Although we are convinced that BMDW is an essential tool to search for donors and cord blood units worldwide we also realize that there are improvements to make to the presently available donor search procedures. For that reason Jeremy Chapman was approached to lead a group of people involved in the different aspects of the search and use of unrelated donors and cord blood units. Many discussions have taken place and agreement has been reached by all that the current situation is not optimal and can be improved and that a global approach is essential in an increasing globalized field where on average 21 stem cell products per day are shipped from one country to another. The biggest challenge for all of us is can we develop business models in such a way that all good things we have accomplished together so far are kept but that necessary improvements are addressed appropriately. Dr. M. Oudshoorn Chairman of Bone Marrow Donors Worldwide June 2011

4 page II Index page Preface I Index II 1 Introduction to Bone Marrow Donors Worldwide (BMDW) Participating Stem Cell Donor Registries and Cord Blood Banks Participating stem cell donor registries Participating cord blood banks/registries 4 3 Number of Stem Cell Donors and Cord Blood Units Number of stem cell donors Number of cord blood units 9 4 Distribution of Stem Cell Donors and Cord Blood Units in the World Distribution of stem cell donors Distribution of cord blood units 15 5 Number of HLA Phenotypes Information Technology Developments in Change Request Registry / third party support and other topics 6.2 Use of BMDW 21 On-line services 7 Board and Staff 23 8 Advisory Committee 24 9 References Publications Abstracts / posters for presentation Invited lectures 25

5 1Introduction to Bone Marrow Donors Worldwide (BMDW) page 1 Bone Marrow Donors Worldwide (BMDW) started as an initiative of the Immunobiology Working Party of the European Group for Blood and Marrow Transplantation (EBMT) in In February 1989 the first edition was distributed, which contained the donor files of eight registries with a total of 150,000 volunteer stem cell donors. The pioneer registries were: Anthony Nolan Research Centre (UK) France Greffe de Moelle (France) National Marrow Donor Program (USA) Europdonor Foundation (The Netherlands) German Registry of Bone Marrow Donors (Germany) Italian Bone Marrow Donor Registry (Italy) Austrian Bone Marrow Donors (Austria) Marrow Donor Program Belgium (Belgium) The original goals of BMDW are still adhered to, but new initiatives have been added. The main goals are: To maximize the chance of finding a stem cell donor/cord blood unit by providing access to all donors and cord blood units available in the world. To minimize the effort put into stem cell donor/cord blood unit searches: only registries/ banks with potential stem cell donors/cord blood units need to be contacted. To provide an estimate of the chance of finding a stem cell donor/cord blood unit for a given patient. To provide advanced search programs to identify partially matched stem cell donors and/ or cord blood units. To facilitate search request advices via Internet. To provide relevant general information for the benefit of the patient. To provide statistics on the increase of donors of different registries, the number of DNA typed donors etc. What is BMDW? BMDW Bone Marrow Donors Worldwide is a service provided by Europdonor Foundation. It provides a listing of HLA phenotypes and other relevant data of unrelated volunteer stem cell donors and cord blood units from participating stem cell donor registries and cord blood banks (CBB s) combined with matching programs. The participants pay an operational fee to have the right to have their own data files uploaded in BMDW and to consult those from other registries and cord blood banks in a secure fashion. BMDW can be used by transplant centres and search coordinators. The procedure for authorisation can be found on BMDW Office The office consists of Europdonor (ED) staff, responsible for keeping BMDW operational, but also to improve the operation as decided by the Editorial Board (EB). NB: the staff size is flexible, which has meant in practical terms that if necessary, extra staff is provided to BMDW by ED.

6 page 2 Editorial Board (EB) of BMDW The Editorial Board is a forum of one representative from each of the registries and cord blood banks, which meets at least once a year. It approves the budget and is authorized by the Europdonor Board to decide on new developments. Advisory Committee (AC) The Advisory Committee consists of eight members elected from and by the EB to assist the BMDW Office and the chair of the Editorial Board to select and prepare topics to be discussed and decided upon by the EB. How is the relationship between the individual registries and/or cord blood banks in relation to BMDW as part of Europdonor regulated? The requirements the registries or CBB s must meet in order to participate in BMDW are described in the house rules (see The services to be delivered by the BMDW Office are defined there as well. They are in brief as follows: The registries/cbb s will submit their data according to a format as determined by the BMDW Office. The clients pay a yearly fee to be agreed upon by the Editorial Board. BMDW verifies the submitted data and makes it available on the website together with matching programs. The BMDW budget depends on the tasks to be performed and is approved in advance by the Editorial Board. How is the relationship between the BMDW Office, the Editorial Board, the Advisory Committee and Europdonor regulated? Briefly the following has been agreed upon: The Board of Europdonor has authorized the Editorial Board to decide on new features and improvements to be developed. The Editorial Board will decide with the BMDW Office as part of Europdonor, the necessary budget to keep BMDW running and to develop the requested new features. The Advisory Committee assists the BMDW Office in preparing the agenda of the Editorial Board meeting and the items on which the Editorial Board has to decide. It will report to the Editorial Board not only the opinions of the majority of the Advisory Committee members, but also minority opinions. The Advisory Committee has the option to consult the IT Working Group of the WMDA. Figure 1 Advisory Committee (AC) Advises IT WG WMDA Advises Europdonor Board (ED) Authorizes Editorial Board (EB) Decides on New developments to be implemented by the BMDW office and the necessary budget

7 2Participating Stem Cell Donor Registries and Cord Blood Banks page Participating stem cell donor registries At the end of 2011, 65 stem cell donor registries from 47 countries participated in BMDW (Table 1). Three new stem cell donor registries joined in BMDW, INCA/REDOME from Brazil, Iranian Stem Cell Donor Program from Iran and DKMS España from Spain. Furthermore, the registry in New Zealand that used to be listed as part of the Australian registry, is now listed separately in BMDW. Together the new registries supply 2,706,205 donors to BMDW. The National Polish Bone Marrow Registry, the Unrelated Bone Marrow Donor Registry (Warsaw) and the Ursula Jaworska Foundation Bone Marrow Donor Registry have merged with the Polish Central Bone Marrow Donor Registry. The Asian Indian Donor Marrow Registry has been deleted from BMDW in December Table 1 PARTICIPATING STEM CELL DONOR REGISTRIES Registry (N = 65) City Country (N = 47) Argentine CPH Donors Registry Buenos Aires Argentina Armenian Bone Marrow Donor Registry Charitable Trust Yerevan Armenia Australian Bone Marrow Donor Registry * Sydney Australia Austrian Bone Marrow Donors Vienna Austria Marrow Donor Program Belgium Mechelen Belgium INCA/REDOME Rio de Janeiro Brazil Bulgarian Bone Marrow Donor Registry Sofi a Bulgaria OneMatch Stem Cell and Marrow Network * Ottawa Canada Hong Kong Bone Marrow Donor Registry (HKBMDR) Hong Kong China New Sunshine Charity Foundation (NSCF) Beijing China Croatian Bone Marrow Donor Registry Zagreb Croatia Cyprus Paraskevaidio Bone Marrow Donor Registry (CPBMDR) Nicosia Cyprus Cyprus Bone Marrow Donor Registry (CBMDR) * Nicosia Cyprus Czech Stem Cells Registry (CSCR) Prague Czech Republic Czech National Marrow Donor Registry (CNMDR) * Plzen Czech Republic The Danish Bone Marrow Donor Registry (DBMDR) Aarhus Denmark Bone Marrow Donors Copenhagen (BMDC) Copenhagen Denmark Finnish Bone Marrow Donor Registry Helsinki Finland France Greffe de Moelle * St-Denis la Plaine France ZKRD - German National Registry of Blood Stem Cell Donors* Ulm Germany Unrelated Hematopoietic Stem Cell Donor Registry Greece Athens Greece Hungarian Bone Marrow Donor Registry Budapest Hungary DATRI Blood Stem Cell Donors Registry Chennai India Iranian Stem Cell Donor Program (ISCDP) Tehran Iran Irish Unrelated Bone Marrow Panel * Dublin Ireland Hadassah Bone Marrow Donor Registry (HBMDR) Jerusalem Israel Ezer Mizion Bone Marrow Donor Registry (EMBMDR) * Petach Tikvah Israel Sheba Medical Center Donor Registry (SMCDR) Tel-Hashomer Israel Italian Bone Marrow Donor Registry * Genova Italy Japan Marrow Donor Program * Tokyo Japan Lithuanian National Bone Marrow Donor Registry Vilnius Lithuania Mexican Bone Marrow Donor Registry (DONORMO) Mexico City Mexico Europdonor Foundation * Leiden The Netherlands New Zealand Bone Marrow Donor Registry * Auckland New Zealand The Norwegian Bone Marrow Donor Registry * Oslo Norway Against Leukemia Foundation Marrow Donor Registry (ALF-MDR) Warsaw Poland Fundacja DKMS Baza Dawcow Komorek Macierzystych Polska Warsaw Poland Central Bone Marrow Donor Registry (POLTransplant) Warsaw Poland Portuguese Bone Marrow Donors Registry (CEDACE) Lisbon Portugal Russian Bone Marrow Donor Registry (RBMDR) Moscow Russian Federation Karelian Registry of Unrel. Donors of Hematopoietic Stem Cells Petrozavodsk Russian Federation Bone Marrow Donors Registry Blood Banks of Russia St. Petersburg Russian Federation Bone Marrow Donor Registry of Samara Region Samara Russian Federation San Marino Bone Marrow Donor Registry Borgo Maggiore Republic San Marino

8 page 4 Figure 2 Participating Stem Cell Donor Registries Europdonor Foundation * Leiden The Netherlands New Zealand Bone Marrow Donor Registry * Auckland New Zealand The Norwegian Bone Marrow Donor Registry * Oslo Norway Against Leukemia Foundation Marrow Donor Registry (ALF-MDR) Warsaw Poland Fundacja DKMS Baza Dawcow Komorek Macierzystych Polska Warsaw Poland PARTICIPATING Central Bone Marrow STEM Donor CELL DONOR Registry REGISTRIES (POLTransplant) Registry Portuguese (N = Bone 65) Marrow Donors Registry (CEDACE) Warsaw City Lisbon Poland Country Portugal(N = 47) Argentine Russian Bone CPH Marrow Donors Donor Registry Registry (RBMDR) Buenos Moscow Aires Argentina Russian Federation Karelian Armenian Registry Bone Marrow of Unrel. Donors Registry of Hematopoietic Charitable Trust Stem Cells Petrozavodsk Yerevan Russian ArmeniaFederation Bone Australian Marrow Bone Donors Marrow Registry Donor Blood Registry Banks * of Russia St. Sydney Petersburg Russian AustraliaFederation Bone Austrian Marrow Bone Donor Marrow Registry Donors of Samara Region Samara Vienna Russian Austria Federation San Marrow Marino Donor Bone Program Marrow Belgium Donor Registry Borgo Mechelen Maggiore Republic BelgiumSan Marino Singapore INCA/REDOME Bone Marrow Donor Programme (BMDP) Singapore Rio de Janeiro Singapore Brazil Slovak Bulgarian National Bone Marrow Bone Marrow Donor Donor Registry Registry Bratislava Sofi a Bulgaria Slovakia OneMatch Slovenia Donor Stem Cell and Marrow Network * Ottawa Ljubljana Canada Slovenia Hong South Kong African Bone Bone Marrow Donor Registry Registry (SABMR) (HKBMDR) Hong Cape Town Kong China South Africa New REDMO, Sunshine Jose Carreras Charity Foundation International (NSCF) Leukemia Foundation Beijing Barcelona China Spain Croatian DKMS Espana Bone Marrow Donor Registry Zagreb Croatia Spain Cyprus The Tobias Paraskevaidio Registry Bone Marrow Donor Registry (CPBMDR) Nicosia Stockholm Cyprus Sweden Cyprus Swiss Blood Bone Stem Marrow Cells Donor Registry (CBMDR) * Nicosia Bern Cyprus Switzerland Czech Buddhist Stem Tzu Cells Chi Stem Registry Cells (CSCR) Center * Prague Hualien City Czech TaiwanRepublic Czech Thai Stem National Cell Donor Marrow Registry Donor Registry (TSCDR) (CNMDR) * Plzen Bangkok Czech Thailand Republic The Ankara Danish University Bone Marrow School of Donor Medicine Registry Unrelated (DBMDR) Blood and Aarhus Denmark Bone Marrow Marrow Donor Donors Registry Copenhagen (BMDC) Copenhagen Ankara Denmark Turkey Finnish Blood and Bone Bone Marrow Donor Donor Registry of Istanbul Medical Fac. Helsinki Istanbul Finland Turkey France Emirates Greffe Bone de Marrow Moelle Donor * Registry St-Denis Sharjah la Plaine France United Arab Emirates ZKRD Anthony - German Nolan * National Registry of Blood Stem Cell Donors* Ulm London Germany United Kingdom British Unrelated Bone Hematopoietic Marrow Registry Stem (BBMR) Cell Donor * Registry Greece Bristol Athens United GreeceKingdom Welsh Hungarian Bone Bone Marrow Marrow Donor Donor Registry Registry * Pontyclun Budapest United Hungary Kingdom SINDOME DATRI Blood Stem Cell Donors Registry Montevideo Chennai Uruguay India National Iranian Stem Marrow Cell Donor Program (NMDP) (ISCDP)* Minneapolis, Tehran MN USA Iran American Irish Unrelated Bone Bone Marrow Marrow Donor Panel Registry * (ABMDR) Mandeville, Dublin LA USA Ireland Caitlin Hadassah Raymond Bone Marrow International Donor Registry (CRIR) (HBMDR) * Worcester, Jerusalem MA USA Israel Gift Ezer of Mizion Life Bone Marrow Foundation Donor Registry (GOL)(EMBMDR) * * Boca Petach Raton, Tikvah FL USA Israel Sheba Medical Center Donor Registry (SMCDR) Tel-Hashomer Israel *) Italian Registry Bone accredited Marrow Donor by Registry the World * Marrow Donor Association Genova (WMDA). Italy Japan Marrow Donor Program * Tokyo Japan Lithuanian National Bone Marrow Donor Registry Vilnius Lithuania The Mexican number Bone of Marrow participating Donor Registry stem cell (DONORMO) donor registries is shown Mexico in Figure City 2. Mexico Europdonor Foundation * Leiden The Netherlands New Number Zealand of registries Bone Marrow Donor Registry * Auckland New Zealand 80The Norwegian Bone Marrow Donor Registry * Oslo Norway 70Against Leukemia Foundation Marrow Donor Registry (ALF-MDR) Warsaw Poland Fundacja DKMS Baza Dawcow Komorek Macierzystych Polska Warsaw Poland 60 Central Bone Marrow Donor Registry (POLTransplant) Warsaw Poland 50Portuguese Bone Marrow Donors Registry (CEDACE) Lisbon Portugal 40Russian Bone Marrow Donor Registry (RBMDR) Moscow Russian Federation Karelian Registry of Unrel. Donors of Hematopoietic Stem Cells Petrozavodsk Russian Federation 30 Bone Marrow Donors Registry Blood Banks of Russia St. Petersburg Russian Federation 20Bone Marrow Donor Registry of Samara Region Samara Russian Federation 10San Marino Bone Marrow Donor Registry Borgo Maggiore Republic San Marino Singapore Bone Marrow Donor Programme (BMDP) Singapore Singapore 0 Slovak National Bone Marrow Donor Registry Bratislava Year Slovakia Slovenia Donor Ljubljana Slovenia South African Bone Marrow Registry (SABMR) Cape Town South Africa REDMO, Jose Carreras International Leukemia Foundation Barcelona Spain DKMS Espana Spain 2.2 Participating The Tobias Registry cord blood banks/registries Stockholm Sweden Swiss Blood Stem Cells Bern Switzerland In Buddhist 2011, 44 Tzu cord Chi Stem blood Cells banks/registries Center * located in 29 countries Hualien participated City Taiwan in BMDW (Table Thai Stem 2). Cell Donor Registry (TSCDR) Bangkok Thailand Four Ankara new University cord blood School banks of Medicine joined Unrelated BMDW, Cyprus Blood and Cord Blood Bank, Iranian Stem Cell Donor Marrow Program, Donor Registry Cord Blood Bank of Samara Region and Anthony Ankara Nolan Cord Turkey Blood Registry. Blood and These Bone Marrow new banks Donor supplied Registry data of Istanbul of 7,448 Medical units Fac. to BMDW. Istanbul Turkey Emirates Bone Marrow Donor Registry Sharjah United Arab Emirates Anthony Nolan * London United Kingdom British Bone Marrow Registry (BBMR) * Bristol United Kingdom Welsh Bone Marrow Donor Registry * Pontyclun United Kingdom SINDOME Montevideo Uruguay National Marrow Donor Program (NMDP) * Minneapolis, MN USA American Bone Marrow Donor Registry (ABMDR) Mandeville, LA USA

9 page 5 The Michigan Blood Cord Blood Bank and the University of Colorado Cord Blood Bank are no longer providing data directly to BMDW but are now providing their data to BMDW through the NMDP network. The Caitlin Raymond International Cord Blood Registry (Cryobanks Cord Blood Bank and Alberta Cord Blood Bank) has withdrawn its data from BMDW. Table 2 PARTICIPATING CORD BLOOD BANKS/REGISTRIES Registry (N = 44) City Country (N = 29) Argentina National Cord Blood Bank Buenos Aires Argentina Australian Cord Blood Registry Sydney Australia Austrian Cord Blood Registry Vienna Austria Belgium Cord Blood Registry (BCBR) Mechelen Belgium Leuven Cord Blood Bank (LCBB) Leuven Belgium Croatian Cord Blood Bank Zagreb Croatia Cyprus Cord Blood Bank Nicosia Cyprus Czech Cord Blood Registry Prague Czech Republic Finnish Cord Blood Registry Helsinki Finland France Greffe de Moelle Cord Blood Registry St-Denis La Plaine France German Branch of the European Cord Blood Bank (GBECBB) Düsseldorf Germany ZKRD - German National Registry of Blood Stem Cell Donors Ulm Germany Hellenic Cord Blood Bank Athens Greece Hadassah-MDA Cord Blood Bank (H-MDACBB) Jerusalem Israel Sheba Medical Centre Cord Blood Registry (SMCCBR) Tel-Hashomer Israel Iranian Stem Cell Donor Program (ISCDP) Tehran Iran Italian Cord Blood Bank Network Genova Italy Tokyo Cord Blood Bank Tokyo Japan Catholic Hematopoietic Stem Cell Bank (KCHSCB) Seoul Republic of Korea Korea Cord Blood Bank (KCBB) Seoul Republic of Korea Mexican Unrelated Cord Blood Bank (BACECU) Mexico City Mexico Europdonor Foundation Leiden The Netherlands Central Cord Blood Registry (POLTransplant) Warsaw Poland Cord Blood Bank of Samara region Samara Russian Federation Eurocord Slovakia Slovak Placental Stem Cell Registry Bratislava Slovakia REDMO Spanish Cord Blood Registry Barcelona Spain The Tobias Registry Stockholm Sweden Swiss Cord Blood Registry Bern Switzerland Alarvita BioLife Corporation Wugu Shiang Taiwan BIONET Corp. Hualien City Taiwan Buddhist Tzu Chi Stem Cells Center Taipei City Taiwan Healthbanks Biotech Co. Ltd. Taipei Taiwan StemCyte, Inc. Taiwan LinKou, Taipei Hsien Taiwan Thai National Cord Blood Bank Bangkok Thailand Ankara University School of Medicine Unrelated Blood and Marrow Donor Registry Ankara Turkey Anthony Nolan Cord Blood Registry London UK British Bone Marrow Registry Cord Blood Bank Bristol UK StemCyte Inc. Covina, CA USA Gift of Life Cord Blood Program (GOL) Boca Raton, FL USA Celgene Cord Blood Bank Cedar Knolls, NJ USA Cleveland Cord Blood Center (CCBC) Cleveland, OH USA National Marrow Donor Program Cord Blood Bank (NMDP) Minneapolis, MN USA National Cord Blood Program, New York Blood Center (NCBP-NYBC) Long Island City, NY USA New Jersey Cord Blood Allendale, NJ USA

10 page 6 The number of participating cord blood banks/registries are shown in Figure 3. Figure 3 Participating Cord Blood Banks/Registries Number of registries Year

11 page 7 3Number of Stem Cell Donors and Cord Blood Units 3.1 Number of stem cell donors The number of HLA-A, -B and HLA-A, -B, -DR typed stem cell donors per registry is shown in Table 3. In Figure 4 the total number of HLA-A, -B and HLA-A, -B, -DR typed stem cell donors per year is given. The number of stem cell donors increased by 3,739,176 from 14,873,946 to 18,613,122 in The large increase is mainly due to the addition of the donors from INCA/REDOME of Brazil. The percentage of HLA-DR typed donors has increased by 5%, from 82% in 2010 to 87% in In the total group of donors the percentage of HLA class I DNA typed donors is 71% and HLA class II DNA typed donors is 82%. Table 3 THE NUMBER OF HLA-A, -B AND HLA-A, -B, -DR AND DNA TYPED STEM CELL DONORS PER REGISTRY Total Number of Percentage HLA-A, -B, of HLA-A, -B, Number of class I Number of class II number -DR typed -DR typed DNA typed DNA typed Registry of donors donors donors donors donors Argentina - Argentine CPH Donors Registry 33,127 28, ,125 28,905 Armenia - Armenian Bone Marrow Donor Registry Charitable Trust 20,274 20,271 > 99 20,274 20,272 Australia - Australian Bone Marrow Donor Registry 174, , , ,470 Austria - Austrian Bone Marrow Donors 62,490 29, ,422 20,146 Belgium - Marrow Donor Program Belgium 56,948 48, ,934 34,853 Brazil - INCA/REDOME 2,548,975 2,539,284 > 99 2,410,182 2,532,908 Bulgaria - Bulgarian Bone Marrow Donor Registry Canada - OneMatch Stem Cell and Marrow Network 312, , , ,251 China - Hong Kong Bone Marrow Donor Registry (HKBMDR) 75,666 57, ,518 39,848 China - New Sunshine Charity Foundation (NSCF) 2,513 39, ,513 2,360 Croatia - Croatian Bone Marrow Donor Registry 25,791 24, ,210 24,209 Cyprus - Cyprus Paraskevaidio Bone Marrow Donor Registry (CPBMDR) 5, , Cyprus - Cyprus, Bone Marrow Donor Registry (CBMDR) 111, ,383 51,332 Czech Republic - Czech National Marrow Donor Registry (CNMDR) 36,531 31, ,002 31,615 Czech Republic - Czech Stem Cells Registry (CSCR) 20,552 9, ,111 9,288 Denmark - The Danish Bone Marrow Donor Registry (DBMDR) 24,979 23, ,394 23,884 Denmark -Bone Marrow Donors Copenhagen (BMDC) 13,172 12, ,238 Finland - Finnish Bone Marrow Donor Registry 19,998 19, ,961 5,436 France - France Greffe de Moelle 196, , , ,479 Germany - ZKRD-German National Registry of Blood Stem Cell Donors 4,409,533 3,376, ,014,805 3,297,905 Greece - Unrelated Hematopoietic Stem Cell Donor Registry Greece 33,737 18, ,378 2,378 Hungary - Hungarian Bone Marrow Donor Registry 5,481 2, ,510 India - DATRI Blood Stem Cell Donors Registry 10,887 10, ,887 10,679 Iran - Iranian Stem Cell Donor Program (ISCDP) Ireland - Irish Unrelated Bone Marrow Panel 20,320 20, ,618 13,288 Israel - Hadassah Bone Marrow Donor Registry (HBMDR) 96,415 65, ,210 64,526 Israel - Ezer Mizion Bone Marrow Donor Registry (EMBMDR) 587, , , ,050 Israel - Sheba Medical Center Donor Registry (SMCDR) 1, Italy - Italian Bone Marrow Donor Registry 334, , , ,473 Japan - Japan Marrow Donor Program 398, , Lithuania - Lithuanian National Bone Marrow

12 page 8 Blood Stem Cell Donors 4,409,533 3,376, ,014,805 3,297,905 Greece - Unrelated Hematopoietic Stem Cell Donor Registry Greece 33,737 18, ,378 2,378 Hungary - Hungarian Bone Marrow Donor Registry 5,481 2, ,510 India THE NUMBER - DATRI Blood OF Stem HLA-A, Cell -B Donors AND HLA-A, Registry -B, -DR AND 10,887 DNA TYPED 10,624 STEM CELL 98 DONORS 10,887 PER REGISTRY 10,679 Iran - Iranian Stem Cell Donor Program (ISCDP) 868 Number 544 of Percentage 63 Number 545 Number 544 Ireland - Irish Unrelated Bone Marrow Panel Total 20,320 HLA-A, 20,199 -B, of HLA-A, 99 -B, of class 12,618 I of class 13,288 II Israel - Hadassah Bone Marrow Donor Registry number -DR typed -DR typed DNA typed DNA typed (HBMDR) Registry of donors 96,415 donors 65,096 donors 68 donors 83,210 donors 64,526 Argentina Israel - Ezer - Argentine Mizion Bone CPH Marrow Donors Donor Registry Registry 33,127 28, ,125 28,905 (EMBMDR) Armenia - Armenian Bone Marrow Donor Registry 587, , , ,050 Israel Charitable - Sheba Trust Medical Center Donor Registry (SMCDR) 20,274 1,769 20, > , , Italy Australia - Italian - Australian Bone Marrow Bone Donor Marrow Registry Donor Registry 334, , , , ,354 62, , ,470 Japan Austria -- Japan Austrian Marrow Bone Donor Marrow Program Donors 398,121 62, ,121 29, , ,146 0 Lithuania Belgium -- Marrow Lithuanian Donor National Program Bone Belgium Marrow 56,948 48, ,934 34,853 Donor Brazil - Registry INCA/REDOME 2,548,975 6,591 2,539,284 6,590 > 99 2,410,182 4,357 2,532,908 6,588 Bulgaria Mexico -- Mexican Bulgarian Bone Bone Marrow Donor Registry Canada (DONORMO) - OneMatch Stem Cell and Marrow Network 312,992 14, ,607 14,172 > , ,251 14,130 China The Netherlands - Hong Kong - Europdonor Bone Marrow Foundation, Donor Registry 39,523 38, ,609 29,077 (HKBMDR) New Zealand - New Zealand Bone Marrow 75,666 57, ,518 39,848 China Donor - Registry New Sunshine Charity Foundation (NSCF) 10,030 2,513 39,848 3, ,513 4,619 2,360 3,718 Croatia Norway - The Croatian Norwegian Bone Bone Marrow Marrow Donor Donor Registry Registry 25,791 28,919 24,422 27, ,210 11,209 24,209 27,540 Cyprus Poland - Against Cyprus Paraskevaidio Leukemia Foundation Bone Marrow Donor Registry (CPBMDR) (ALF 12,114 5,888 7, ,424 7,769 7, Cyprus Poland - Fundacja Cyprus, Bone DKMS Marrow Baza Dawcow Donor Registry Komorek (CBMDR) Macierzystych Polska 111, , , > ,360 89, ,694 51,332 Czech Poland Republic - Central - Bone Czech Marrow National Donor Marrow Registry Donor Registry (POLTransplant) (CNMDR) 36,531 76,121 31,660 60, ,884 8,002 31,615 59,481 Czech Portugal Republic - Portuguese - Czech Bone Stem Marrow Cells Registry Donors Registry (CSCR) 20,552 9, ,111 9,288 Denmark (CEDACE)- The Danish Bone Marrow Donor Registry 272, , , ,612 (DBMDR) Russian Federation - Russian Bone Marrow 24,979 23, ,394 23,884 Denmark Donor Registry -Bone (RBMDR) Marrow Donors Copenhagen (BMDC) 13,172 6,267 12, , Finland Russian - Federation Finnish Bone - Karelian Marrow Registry Donor Registry of Unrel. 19,998 19, ,961 5,436 France Donors - of France Hematopoietic Greffe de Stem Moelle Cells 196,025 2, , ,904 2, , Germany Russian Federation - ZKRD-German - Bone National Marrow Registry Donors of Blood Registry Stem Blood Cell Banks Donors of Russia 4,409, ,376, > ,014, ,297, Greece Russian - Federation Unrelated Hematopoietic - Bone Marrow Stem Donor Cell Registry Donor of Samara Registry Region Greece 33,737 3,381 18, ,3780 2, Hungary Republic - San Hungarian Marino - Bone San Marrow Marino Bone Donor Marrow Registry 5,481 2, ,510 India Donor - Registry DATRI Blood Stem Cell Donors Registry 10, , > , , Iran Singapore - Iranian - Singapore Stem Cell Bone Donor Marrow Program Donor (ISCDP) Ireland Programme - Irish (BMDP) Unrelated Bone Marrow Panel 20,320 11,057 20,199 11,053 > 99 12,618 11,057 13,288 11,053 Israel Slovakia - Hadassah - Slovak National Bone Marrow Bone Marrow Donor Donor Registry Registry 2,799 2, ,287 2,620 (HBMDR) Slovenia -Slovenia Donor 96,415 12,453 65,096 12,444 > ,210 11,844 64,526 12,445 Israel South - Africa Ezer - Mizion South Bone African Marrow Bone Marrow Donor Registry (EMBMDR) (SABMR) 587,943 64, ,610 10, , ,050 8,758 Israel Spain - Sheba REDMO, Medical Jose Center Carreras Donor International Registry (SMCDR) 1, Italy Leukemia - Italian Foundation Bone Marrow Donor Registry 334,426 91, ,932 60, ,354 37, ,473 43,882 Japan Spain - DKMS Japan España Marrow Donor Program 398,121 1, ,121 1, , ,204 0 Lithuania Sweden -- The Lithuanian Tobias Registry National Bone Marrow 40,150 24, ,909 23,105 Donor Switzerland Registry - Swiss Blood Stem Cells 35,592 6,591 35,430 6,590 > 99 19,843 4,357 35,217 6,588 Mexico Taiwan - Buddhist Mexican Bone Tzu Chi Marrow Stem Donor Cells Center Registry 323, , , ,739 (DONORMO) Thailand - Thai Stem Cell Donor Registry (TSCDR) 109,119 14, ,627 14,172 > , ,509 14,130 The Turkey Netherlands - Ankara University - Europdonor School Foundation, of Medicine 39,523 38, ,609 29,077 New Unrelated Zealand Blood - New and Marrow Zealand Donor Bone Registry Marrow (TRAN) 5,183 3, ,935 3,662 Donor Turkey Registry - Blood and Bone Marrow Donor Registry of 10,030 3, ,619 3,718 Norway Istanbul - Medical The Norwegian Fac. (BBMDR-IMF) Bone Marrow Donor Registry 28,919 25,436 27, , ,5400 Poland UK - Anthony - Against Nolan Leukemia Foundation Marrow 437, , , ,777 Donor UK - British Registry Bone (ALF Marrow MDR) Registry (BBMR), 318,290 12, ,132 7, ,697 7, ,856 7,877 Poland UK - Welsh - Fundacja Bone Marrow DKMS Baza Donor Dawcow Registry Komorek 51,373 51, ,702 51,373 Macierzystych United Arab Emirates Polska - Emirates Bone Marrow 156, ,694 > , ,694 Poland Donor Registry - Central Bone Marrow Donor Registry (POLTransplant) Uruguay - SINDOME 76, , , , Portugal USA - American - Portuguese Bone Bone Marrow Marrow Donor Donors Registry Registry (CEDACE) (ABMDR) 272,924 29, ,057 3, , ,612 1,989 Russian USA - Caitlin Federation Raymond - Russian International Bone Registry Marrow (CRIR) 204, , , ,821 USA Donor - Gift Registry of Life (RBMDR) Bone Marrow Foundation (GOL) 190,637 6, , , , USA Russian - National Federation Marrow - Karelian Donor Registry Program of (NMDP) Unrel. 6,383,832 5,780, ,712,184 5,673,663 Total Donors of Hematopoietic Stem Cells 18,613,122 2,719 16,103, % 8 13,251,943 2,000 15,186, Russian Federation - Bone Marrow Donors

13 Figure 4 Total number of HLA-A, -B and HLA-A, -B, -DR typed stem cell donors Figure 5 The number of stem cell donors added to the database per year Istanbul Medical Fac. (BBMDR-IMF) 25, UK - Anthony Nolan 437, , , ,777 UK - British Bone Marrow Registry (BBMR), 318, , , ,856 page 9 UK - Welsh Bone Marrow Donor Registry 51,373 51, ,702 51,373 United THE NUMBER Arab Emirates OF HLA-A, - Emirates -B AND Bone HLA-A, Marrow -B, -DR AND DNA TYPED STEM CELL DONORS PER REGISTRY Donor Registry 45 Number 45 of Percentage 100 Number 0 Number 0 Uruguay - SINDOME Total 510 HLA-A, 510 -B, of HLA-A, 100 -B, of class 510 I of class 510 II USA - American Bone Marrow Donor Registry number -DR typed -DR typed DNA typed DNA typed (ABMDR) Registry of donors 29,635 donors 3,140 donors 11 donors 0 donors 1,989 Argentina USA - Caitlin - Argentine Raymond CPH International Donors Registry (CRIR) 204,807 33, ,702 28, ,757 33, ,821 28,905 USA Armenia - Gift - of Armenian Life Bone Bone Marrow Marrow Foundation Donor Registry (GOL) 190, , , ,778 USA Charitable - National Trust Marrow Donor Program (NMDP) 6,383,832 20,274 5,780,034 20,271 > ,712,184 20,274 5,673,663 20,272 Total Australia - Australian Bone Marrow Donor Registry 18,613, ,702 16,103, ,292 87% 81 13,251,943 62,529 15,186, ,470 Austria - Austrian Bone Marrow Donors 62,490 29, ,422 20,146 Belgium - Marrow Donor Program Belgium 56,948 48, ,934 34,853 Brazil - INCA/REDOME 2,548,975 2,539,284 > 99 2,410,182 2,532,908 Bulgaria Number - of Bulgarian stem cell Bone donors Marrow (x million) Donor Registry Canada Number - OneMatch above bars Stem is % HLA-A, Cell -B, and -DR Marrow typed stem Network cell donors 312, , ,486 HLA-A,-B,-DR 244,251 China - Hong Kong Bone Marrow Donor Registry (HKBMDR) 75,666 57, HLA-A,-B 33,518 39, China - New Sunshine Charity Foundation (NSCF) 2,513 39, ,513 2, Croatia - Croatian Bone Marrow Donor Registry 25, , ,210 24, Cyprus - Cyprus Paraskevaidio Bone Marrow Donor Registry (CPBMDR) , Cyprus - Cyprus, Bone Marrow Donor 44 Registry , (CBMDR) , ,383 51, Czech Republic 24-25Czech National Marrow Donor Registry (CNMDR) 36,531 31, ,002 31,615 0 Czech Republic - Czech Stem Cells Registry (CSCR) 20,552 9,338 Year 45 2,111 9,288 Denmark - The Danish Bone Marrow Donor Registry (DBMDR) 24,979 23, ,394 23,884 Denmark -Bone Marrow Donors Copenhagen (BMDC) 13,172 12, , The Finland increase - Finnish of Bone the Marrow number Donor of stem Registry cell donors 19,998 per year 19,502 is given in 98 Figure 5. The 3,961 number 5,436 of France additional - France donors Greffe de (3,739,176) Moelle in the database 196,025 in ,283 is more than 92 in ,904 (1,297,548) 170,479 mainly Germany due - ZKRD-German to the addition National of Registry the Brazilian of donors. On average there has been an increase of Blood 1,574,986 Stem Cell donors Donors per year over the last five 4,409,533 years ( ). 3,376, ,014,805 3,297,905 Greece - Unrelated Hematopoietic Stem Cell Donor Registry Greece 33,737 18, ,378 2,378 Hungary Number - Hungarian of stem cell Bone donors Marrow (x thousand) Donor Registry added per year 5,481 2, , India - DATRI Blood Stem Cell Donors Registry 10,887 10, ,887 10, Iran - Iranian Stem Cell Donor Program (ISCDP) Ireland - Irish Unrelated Bone Marrow Panel 20,320 20, ,618 13, Israel - Hadassah Bone Marrow Donor Registry 2500 (HBMDR) 96,415 65, ,210 64, Israel - Ezer Mizion Bone Marrow Donor Registry (EMBMDR) 587, , , , Israel - Sheba Medical Center Donor Registry (SMCDR) 1, Italy - Italian Bone Marrow Donor Registry 334, , , , Japan - Japan Marrow Donor Program 398, , Lithuania - Lithuanian National Bone Marrow 0 Donor Registry 6,591 6,590 > 99 Year 4,357 6,588 Mexico - Mexican Bone Marrow Donor Registry (DONORMO) 14,175 14,172 > ,130 The Netherlands - Europdonor Foundation, 39,523 38, ,609 29, Number New Zealand of cord - New blood Zealand units Bone Marrow Donor Registry 10,030 3, ,619 3,718 The Norway number - The Norwegian of HLA-A, Bone -B Marrow and Donor HLA-A, Registry -B, -DR 28,919 typed cord 27,992 blood units 97 per cord 11,209 blood bank/ 27,540 registry Poland - is Against shown Leukemia in Table Foundation 4. In 2011 Marrow more than half a million cord blood units are in BMDW. The Donor cord Registry blood (ALF units MDR) are practically all fully typed 12,114 for HLA-A, 7,877 -B and 65 -DR, in addition 7,769 73% 7,877 is class Poland I DNA - Fundacja typed DKMS and Baza 92% Dawcow of the Komorek units is class II DNA typed. The total nucleated cell count is Macierzystych given for over Polska 99% of the units and for 84% 156,362 of the units 155,694 the net > 99 volume collected 156, ,694 is Poland provided. - Central In Bone Table Marrow 5 the Donor mean Registry number of total nucleated cells (TNC) of the cord blood units (POLTransplant) in the cord blood banks is given. For all cord 76,121 blood 60,004 units in BMDW 79 the 34,884 mean number 59,481 of Portugal TNC is - Portuguese x 10 Bone and Marrow the Donors median Registry of TNC is 99.2 x (CEDACE) 272, , , ,612 Russian Federation - Russian Bone Marrow Donor Registry (RBMDR) 6, Russian Federation - Karelian Registry of Unrel. Donors of Hematopoietic Stem Cells 2, , Russian Federation - Bone Marrow Donors

14 page 10 Table 4 THE NUMBER OF HLA-A, -B AND HLA-A, -B, -DR TYPED CORD BLOOD UNITS PER CORD BLOOD BANK/REGISTRY Number of Total HLA-A, -B, number -DR typed Number of class I DNA typed Number of class II DNA typed Registry of units units units units Argentina Argentina National Cord Blood Bank 1,850 1,849 1,850 1,849 Australia - Australian Cord Blood Registry 24,556 24,556 19,225 24,556 Austria - Austrian Cord Blood Registry 1,284 1,284 1,284 1,284 Belgium - Belgium Cord Blood Registry (BCBR) 8,275 8,275 6,030 8,227 Belgium - Leuven Cord Blood Bank (LCBB) 7,447 7,447 7,438 7,437 Croatia - Croatian Cord Blood Bank 1,503 1,503 1,503 1,503 Cyprus - Cyprus Cord Blood Bank (CCBB) 1,403 1,403 1,403 1,403 Czech Republic - Czech Cord Blood Registry CSCR 3,741 3,741 3,624 3,739 Finland - Finnish Cord Blood Registry 3,224 3,224 1,445 3,224 France - France Greffe de Moelle Cord Blood Registry 15,817 15,817 10,472 15,322 Germany - German Branch of the European Cord Blood Bank (GBECBB) 11,977 11,977 10,607 11,970 Germany - German National Registry of Blood Stem Cell Donors (ZKRD) 16,470 16,470 12,783 16,469 Greece - Hellenic Cord Blood Bank (HCBB) 1,176 1, Iran - Iranian Stem Cell Donor Program (ISCDP) 1,285 1,276 1,285 1,276 Israel - Hadassah-MDA Cord Blood Bank (H-MDACBB) 6,529 6,527 6,527 6,526 Israel - Sheba Medical Centre Cord Blood Registry (SMCCBR) 2,170 2,167 2,170 2,167 Italy - Italian Cord Blood Bank Network 26,570 26,568 18,268 26,566 Japan - Tokyo Cord Blood Bank 4,443 4, ,443 Republic of Korea - Korea Cord Blood Bank (KCBB) 21,775 21, Republic of Korea - Catholic Hematopoietic Stem Cell Bank (KCHSCB) 1,869 1, ,869 Mexico - Mexican Unrelated Cord Blood Bank (BACECU) The Netherlands - Europdonor Foundation 3,098 3,098 2,495 3,093 Poland - Central Cord Blood Registry (POLTransplant) Russian Federation - Cord Blood Bank of Samara region 4,193 4,155 4,193 4,155 Slovakia - Eurocord Slovakia, Slovak Placental Stem Cell Registry 1,737 1,737 1,179 1,179 Spain - REDMO Spanish Cord Blood Registry 51,719 51,719 38,579 47,756 Sweden - The Tobias Registry 1,956 1,956 1,956 1,956 Switzerland - Swiss Cord Blood Registry 3,645 3,645 3,640 3,645 Taiwan - Alarvita BioLife Corporation Taiwan - BIONET Corp. 27,081 27,081 27,081 27,080 Taiwan - Buddhist Tzu Chi Stem Cells Center 14,215 14,213 12,658 12,727 Taiwan - Healthbanks Biotech Co.Ltd. 5,709 5,709 5,709 5,709 Taiwan - StemCyte, Inc. T aiwan 9,551 9,537 9,551 9,537 Thailand - Thai National Cord Blood Bank 1,740 1, Turkey - Ankara University School of Medicine Unrelated Blood and Marrow Donor Registry UK - Anthony Nolan Cord Blood Registry UK - British Bone Marrow Registry Cord Blood Bank (BBMR) 14,834 14,833 14,764 14,833 USA - Celgene Cord Blood Bank 3,861 3,861 3,861 3,861 USA - Cleveland Cord Blood Center (CCBC) USA - Gift of Life Cord Blood Program (GOL) USA - National Cord Blood Program, New York Blood Center (NCBP-NYBC) 56,581 56,581 1,587 48,815 USA - National Marrow Donor Program Cord Blood Bank (NMDP) 120, , , ,089 USA - New Jersey Cord Blood 1,702 1,699 1,702 1,699 USA - StemCyte Inc 18,878 18,877 18,878 18,877 Total 506, , , ,009

15 page 11 The steady increase of cord blood units in BMDW is shown in Figure 6. The total number of cord blood units at the end of 2011 is 506,819. Figure 6 Total numbers of cord blood units Figure 7 The number of cord blood units added to the database per year Table 5 Number of cord blood units (x thousand) The number of cord blood units per year is given in Figure 7. The number of cord blood units added to the database in 2011 is 53,732. Number of cord blood units (x thousand) added per year THE MEAN NUMBER OF TOTAL NUCLEATED CELLS OF THE CORD BLOOD UNITS IN THE CORD BLOOD BANKS/REGISTRIES Registry Total number of units Mean number of TNC x 10 7 Slovakia - Eurocord Slovakia Slovak Placental Stem Cell Registry 1, Russian Federation - Cord Blood Bank of Samara region 4, USA - Cleveland Cord Blood Center (CCBC) Sweden - The Tobias Registry 1, France - France Greffe de Moelle Cord Blood Registry 15, USA - StemCyte Inc. 18, Israel - Sheba Medical Centre Cord Blood Registry (SMCCBR) 2, Italy - Italian Cord Blood Bank Network 26, Belgium - Belgium Cord Blood Registry (BCBR) 8, UK - Anthony Nolan Cord Blood Registry Czech Republic - Czech Cord Blood Registry CSCR 3, Spain - REDMO Spanish Cord Blood Registry 51, Germany - German Branch of the European Cord Blood Bank (GBECBB) 16, USA - National Marrow Donor Program Cord Blood Bank (NMDP) 120, Israel - Hadassah-MDA Cord Blood Bank (H-MDACBB) 6, The Netherlands - EuroCord Nederland Foundation 3, Poland - Central Cord Blood Registry (POLTransplant) Switzerland - Swiss Cord Blood Registry 24, Australia - Australian Cord Blood Registry 1, Cyprus - Cyprus Cord Blood Bank (CCBB) 1, Republic of Korea - Catholic Hematopoietic Stem Cell Bank (KCHSCB) 7, Belgium - Leuven Cord Blood Bank (LCBB) 7, Year Year

16 page 12 UK - Anthony Nolan Cord Blood Registry Czech Republic - Czech Cord Blood Registry CSCR 3, Spain - REDMO Spanish Cord Blood Registry 51, Germany - German Branch of the European Cord Blood Bank (GBECBB) 16, USA THE - MEAN National NUMBER Marrow Donor OF TOTAL Program NUCLEATED Cord Blood CELLS Bank OF (NMDP) THE CORD BLOOD 120,148 UNITS IN Israel THE CORD - Hadassah-MDA BLOOD BANKS/REGISTRIES Cord Blood Bank (H-MDACBB) 6, The Netherlands - EuroCord Nederland Foundation Total number 3,098 Mean number Poland Registry - Central Cord Blood Registry (POLTransplant) of units 490 of TNC x 7 Switzerland Slovakia - Eurocord - Swiss Slovakia Cord Blood Slovak Registry Placental Stem Cell Registry 24,556 1, Australia Russian Federation - Australian - Cord Blood Bank Registry of Samara region 1,403 4, Cyprus USA - Cleveland - Cyprus Cord Blood Bank Center (CCBB) (CCBC) 1, Republic Sweden - of The Korea Tobias - Catholic Registry Hematopoietic Stem Cell Bank (KCHSCB) 7,572 1, Belgium France - - France Leuven Greffe Cord de Blood Moelle Bank Cord (LCBB) Blood Registry 15,817 7, USA - National StemCyte Cord Inc. Blood Program, New York Blood Center (NCBP-NYBC) 18,878 56, Israel Taiwan - Sheba - StemCyte, Medical Inc. Centre Taiwan Cord Blood Registry (SMCCBR) 2,170 9, Italy Croatia - Italian - Croatian Cord Cord Blood Blood Bank Bank Network 26,570 1, Belgium Argentina - Belgium Argentina Cord National Blood Registry Cord Blood (BCBR) Bank 8,275 1, UK USA - - Anthony New Jersey Nolan Cord Blood Registry 1, Czech Germany Republic - German - Czech National Cord Registry Blood Registry of Blood CSCR Stem Cell Donors (ZKRD) 11,977 3, Spain Finland - REDMO - Finnish Spanish Cord Blood Cord Registry Blood Registry 51,719 3, Germany UK - British - German Bone Marrow Branch Registry of the European Cord Blood Cord Bank Blood (BBMR) Bank (GBECBB) 16,470 14, USA - National Gift of Life Marrow Cord Blood Donor Program (GOL) Cord Blood Bank (NMDP) 120, Israel Austria - - Hadassah-MDA Austrian Cord Blood Cord Blood Registry Bank (H-MDACBB) 6,529 1, The Republic Netherlands of Korea -- EuroCord Korea Cord Nederland Blood Bank Foundation (KCBB) 21,775 3, Poland Taiwan - Central Healthbanks Cord Blood Biotech Registry Co. Ltd. (POLTransplant) 5, Switzerland USA - Celgene - Swiss Cord Blood Cord Blood Bank Registry 24,556 3, Australia Iran - Iranian - Australian Stem Cell Cord Donor Blood Program Registry (ISCDP) 1,403 1, Cyprus Mexico - Cyprus Mexican Cord Unrelated Blood Bank Cord Blood (CCBB) Bank (BACECU) 1, Republic Taiwan - of BIONET Korea Corp. - Catholic Hematopoietic Stem Cell Bank (KCHSCB) 27,081 7, Belgium Taiwan -- Buddhist Leuven Cord Tzu Chi Blood Stem Bank Cells (LCBB) Center 14,215 7, USA Thailand - National - Thai Cord National Blood Cord Program, Blood New Bank York Blood Center (NCBP-NYBC) 56,581 1, Taiwan Japan -- Tokyo StemCyte, Cord Inc. Blood Taiwan Bank 9,551 4, Croatia Taiwan - Alarvita Croatian BioLife Cord Blood Corporation Bank 1, Argentina Turkey - Ankara Argentina University National School Cord of Blood Medicine Bank Unrelated Blood and 1, USA Marrow - New Donor Jersey Registry Cord Blood 1, Germany Greece - Hellenic - German Cord National Blood Registry Bank (HCBB) of Blood Stem Cell Donors (ZKRD) 11,977 1, Finland - Finnish Cord Blood Registry 3, UK - British Bone Marrow Registry Cord Blood Bank (BBMR) 14, USA - Gift of Life Cord Blood Program (GOL) Austria - Austrian Cord Blood Registry 1, Republic of Korea - Korea Cord Blood Bank (KCBB) 21, Taiwan - Healthbanks Biotech Co. Ltd. 5, USA - Celgene Cord Blood Bank 3, Iran - Iranian Stem Cell Donor Program (ISCDP) 1, Mexico - Mexican Unrelated Cord Blood Bank (BACECU) Taiwan - BIONET Corp. 27, Taiwan - Buddhist Tzu Chi Stem Cells Center 14, Thailand - Thai National Cord Blood Bank 1, Japan - Tokyo Cord Blood Bank 4, Taiwan - Alarvita BioLife Corporation Turkey - Ankara University School of Medicine Unrelated Blood and Marrow Donor Registry Greece - Hellenic Cord Blood Bank (HCBB) 1,

17 page 13 4Distribution of Stem Cell Donors and Cord Blood Units in the World 4.1 Distribution of stem cell donors As shown in Figure 8, 38% of the donors reside in North America, 37% in Europe, 14% in South America, 10% in Asia and the remaining 1% originates from other continents. Due to the large amount of Brazilian donors added to BMDW in 2011 the distribution of donors in the world has changed significantly. Figure 8 The distribution of stem cell donors per continent Other 1.3% South America 14% Asia 9.7% Europe 37% North America 38% Figure 9 shows the distribution of stem cell donors in the world and in Europe. Figure 9 Distribution of stem cell donors in the world < 20,000 donors Bulgaria, Finland, Hungary, India, Iran, Lithuania, Mexico, New Zealand, Russian Federation, Republic San Marino, Singapore, Slovakia, Slovenia, United Arab Emirates, Uruguay 20, ,000 donors Argentina, Armenia, Austria, Belgium, China, Croatia, Czech Republic, Denmark, Greece, Ireland, Norway, South Africa, Spain, Sweden, Switzerland, The Netherlands, Turkey > 100,000 donors Australia, Canada, Cyprus, France, Israel, Italy, Japan, Poland, Portugal, Taiwan, Thailand, United Kingdom > 1,000,000 donors Brazil, Germany and USA

18 page 14 Table 6 contains the number of stem cell donors per 10,000 inhabitants sorted by HLA-A, -B, -DR. The mean number of HLA-A, -B, -DR typed donors per 10,000 inhabitants in the participating countries is 92.0 and median is 35.7; for HLA-A, -B plus HLA-A, -B, -DR donors the mean is and median is It is obvious that there are still large differences in the number of donors per 10,000 inhabitants between countries. Of the world population 0.3% is registered as a hematopoietic stem cell donor. Table 6 THE NUMBER OF STEM CELL DONORS PER 10,000 INHABITANTS (SORTED BY HLA-A, -B, -DR PER 10,000 INHABITANTS) Number of inhabitants Number of stem cell donors Number of donors per 10,000 inhabitants Country x 10 6 (*) ABDR Total ABDR Total Israel , , ,072.1 Cyprus , , ,519.0 Germany ,376,999 4,409, Republic San Marin Portugal , , USA ,129,866 6,808, Brazil ,539,284 2,548, Taiwan, Province of China , , United Kingdom , , Canada , , Australia , , Armenia ,271 20, Denmark ,341 38, Slovenia ,444 12, Norway ,992 28, Poland , , Croatia ,422 25, Ireland ,199 20, Switzerland ,430 35, Belgium ,346 56, Italy , , Czech Republic ,998 57, Finland ,502 19, Austria ,150 62, Japan , , France , , Sweden ,269 40, Singapore ,053 11, The Netherlands ,175 39, Lithuania 3.6 6,590 6, Greece ,038 33, Thailand , , Spain ,206 92, New Zealand 4.0 3,823 10, Argentina ,908 33, Slovakia 5.4 2,620 2, Hungary ,761 5, South Africa ,063 64, Uruguay Mexico ,172 14, Bulgaria Turkey ,022 30, China 1, ,289 78, United Arab Emirates Russian Federation ,338 13, India 1, ,624 10, Iran, Islamic Republic of

19 page Distribution of cord blood units As shown in Figure 10, the majority of the cord blood units are stored in North American (40%) and European (35%) cord blood banks. The remaining cord blood units are from Asia (20%), Australia/Oceania (5%) and South America (0.4%). Figure 10 Distribution of cord blood units per continent South America 0.4% Australia / Oceania 4.8% Asia 20.2% North America 40% Europe 34.6% Figure 11 shows the distribution of unrelated cord blood units in the world and in Europe. Figure 11 Distribution of cord blood units in the world < 10,000 units Argentina, Austria, Croatia, Cyprus, Czech Republic, Finland, Greece, Israel, Japan, Mexico, the Netherlands, Poland, Russian Federation, Slovakia, Sweden, Switzerland, Thailand, Turkey 10,000-20,000 units Belgium, France, United Kingdom > 20,000 units Australia, Germany, Italy, Republic of Korea, Spain, Taiwan, USA

20 page 16 The number of cord blood units per 10,000 inhabitants is given in Table 7. The data is sorted by the number of cord blood units per 10,000 inhabitants, starting with the highest number. The mean number of cord blood units per 10,000 inhabitants in the participating countries is 5.6 and the median is 3.3. Table 7 THE NUMBER OF CORD BLOOD UNITS PER 10,000 INHABITANTS Country Number of inhabitants Number of cord blood Number of cord blood units per 10,000 x 10 6 (*) units inhabitants Taiwan, Province of China , Cyprus 0.8 1, Belgium , Israel 6.2 8, Spain , Australia , USA , Finland 5.2 3, Republic of Korea , Switzerland 7.5 3, Italy , Czech Republic , Germany , Croatia 4.5 1, Slovakia 5.4 1, France , United Kingdom , Sweden 9.0 1, The Netherlands , Austria 8.2 1, Greece , Argentina , Japan , Russian Federation , Thailand , Iran, Islamic Republic of , Poland Mexico < 0.03 Turkey < 0.0 * Data extracted from CIA factbook 2010.

21 page 17 5Number of HLA Phenotypes Figure 12 states the number of stem cell donors and cord blood units typed for HLA-A, -B, -DR split antigens, the number of different HLA-A, -B, -DR split phenotypes and the number of unique phenotypes. Unique phenotypes are defined as occurring only once in the BMDW database. In 2011 there were 11,461,779 HLA-A, -B, -DR split typed stem cell donors and cord blood units representing 1,414,334 different phenotypes. Forty-seven percent of these were unique phenotypes (665,684). These donors were mainly typed by serology or low resolution DNA typing, the number of unique phenotypes rises even more, if typing is performed on the allele level for the HLA-A, -B, -C, -DR and -DQ loci. Figure 12 Number of stem cell donors and cord blood units per year Number of stem cell donors and cord blood units and phenotypes (x million) HLA-A, -B, -DR split typed stem cell donors and cord blood units HLA-A, -B, -DR different phenotypes Figure 13 Increase in the number of different phenotypes added to the BMDW database Figure 13 shows that new stem cell donors and cord blood units still add new HLA-A, -B, -DR split phenotypes to the BMDW database. Number of different phenotypes (x thousand) Year HLA-A, -B, -DR unique phenotypes ,000 1,500 2,000 2,500 3, ,000 4,500 5,000 5,500 6,000 6,500 7,000 7,500 8,000 8,500 9,000 9,500 10,000 10,500 11,000 11,500 12,000 The number of different new HLA-A, -B, -DR phenotypes per 1,000 new stem cell donors and cord blood units is given in Figure 14. In 1990 more than half of the new donors and cord blood units had an HLA-A, -B, -DR split phenotype that was not yet present in the BMDW database. In 2011 one out of ten donors and cord blood units still add a new HLA-A, -B, -DR split phenotype to the database. In 2010 this was only one out of fifteen. The reason for this difference is due to the addition of well over two million Brazilian donors providing BMDW with a high number of new HLA-A, -B, -DR split phenotypes.

22 page 18 This effect is also seen in Figure 14. Figure 14 Number of different HLA-A, -B, -DR split phenotypes per thousand new stem cell donors and cord blood units Number of different phenotypes per thousand new stem cell donors and cord blood units The relative contribution to BMDW of stem cell donors per country with an HLA-A, -B, -DR split phenotype is shown in Figure 15. There are large differences between the countries; countries on the left-hand side of the curve such as South Africa, India, Mexico, Brazil, Singapore and Argentina have a relatively high contribution of new HLA phenotypes to BMDW, while countries on the right-hand side such as Ireland, Lithuania, Norway, Sweden, Slovenia and Denmark added relatively few new HLA phenotypes to BMDW. This means that many of the phenotypes of those countries are already in BMDW, which is of course good news for the patients in those countries Year Figure 15 The relative percentage of unique HLA-A, -B, -DR split phenotypes of stem cell donors per country contributed to the entire database in BMDW South Africa Relative percentage of unique phenotypes in 2011 India Mexico Brazil Singapore Argentina Thailand Armenia New Zealand Spain Greece Turkey Russian Federation United States France Italy Cyprus China San Marino Switzerland Poland Hungary Portugal United Kingdom Taiwan, Province of China Remark: Bulgaria, Iran, United Arab Emirates and Uruguay had too few HLA-A, -B, -DR split typed donors to be depicted in Figure 15. Israel Slovakia Germany Canada Czech Republic Belgium Croatia Japan Netherlands Austria Finland Australia Denmark Slovenia Sweden Norway Lithuania Ireland Country Figure 16 depicts the relative contribution of cord blood units with new HLA phenotypes in the entire BMDW database. Figure 17 shows the percentage of unique HLA-A, -B, -DR split phenotypes of stem cell donors contributed to the donor BMDW file (excluding cord blood units). The difference between Figure 15 (entire BMDW database) and Figure 17 (only the stem cell donor data in BMDW) is minimal. In virtually all countries the cord blood units have a much higher relative contribution of new HLA phenotypes to BMDW than the stem cell donors of the same country, indicating the success of the cord blood banks in recruiting cord blood units from minority groups.

23 page 19 Figure 16 The relative percentage of unique HLA-A, -B, -DR split phenotypes of cord blood units per country contributed to the entire database in BMDW Figure 17 The relative percentage of unique HLA-A, -B, -DR split phenotypes of stem cell donors per country contributed to the stem cell donor database in BMDW Relative percentage of unique phenotypes in Remark: Turkey had too few HLA-A, -B, -DR typed cord blood units to be depicted in Figure South Africa Thailand Mexico Greece France Spain United States Switzerland Argentina Italy United Kingdom Netherlands Cyprus Iran Korea Relative percentage of unique phenotypes in 2011 India Mexico Brazil Singapore Argentina Thailand New Zealand Armenia Russian Federation Spain Greece Turkey Russian Fed. United States France Italy China Cyprus San Marino Switzerland Hungary Poland Taiwan Portugal Slovakia United Kingdom Sweden Australia Czech Republic Germany Belgium Austria Taiwan Croatia Israel Slovakia Japan Poland Finland Czech Republic Belgium Croatia Japan Netherlands Finland Austria Australia Denmark Slovenia Sweden Norway Lithuania Ireland Norway In Figure 18 the percentage of unique HLA-A, -B, -DR split phenotypes of cord blood units contributed to the cord blood unit data only (excluding donors) is given. The large difference between Figures 16 and 18 indicate that the number of phenotypes of the cord blood units within BMDW is still limited. Israel Germany Canada Country Remark: Bulgaria, Iran, United Arab Emirates and Uruguay had too few HLA-A, -B, -DR split typed donors to be depicted in Figure 16. Country Figure 18 The relative percentage of unique HLA-A, -B, -DR split phenotypes of cord blood units per country contributed to the cord blood unit database in BMDW Relative percentage of unique phenotypes in Remark: Turkey had too few HLA-A, -B, -DR typed cord blood units to be depicted in Figure Thailand Greece Mexico Spain France Switzerland Italy Argentina United States Cyprus Russian Federation Iran United Kingdom Israel Croatia Poland Netherlands Germany Czech Republic Australia Slovakia Belgium Austria Sweden Korea, Republic of Japan Finland Taiwan Country

24 page 20 6Information Technology 6.1 Developments in 2011 One of the main topics for 2010 was the new WHO Nomenclature, as introduced in April For BMDW this still had an effect in 2011, since there was still a group of registries and cord blood banks, that had not yet migrated to the new nomenclature. At the end of 2011, the following registries and cord blood bank have not migrated: Japan-Tokyo Cord Blood Bank, San Marino, USA-New York Cord Blood Bank, and USA-ABMDR. Change Requests: The BMDW Office welcomes feedback and suggestions for improvements. Change requests may be submitted to the BMDW Office using the BMDW Change Request Form 1). The BMDW Office will evaluate the change requests received and if needed consult the Advisory Committee and ask the Editorial Board for approval. Next to the regular maintenance tasks and updates of the BMDW database, the following changes have been implemented or are in progress. CRF001 Two user levels for donor details: registry users are able to see the donor id s in the search results. CRF006 Registry ID s: Cooperation with the WMDA IT Working Group has resulted in a proposal for a new standard for Registry and Cord Blood Bank ID s. A new proposal and possible solution is still being evaluated. CRF009 Local use of match: registries and cord blood banks now have the option to match on their own donors. CRF022 Printing multiple pages: printing long search reports with many donors or cord blood units is a problem for some internet browsers. An option to generate a PDF of the search results is currently work in progress. CRF026 Ranking option DRB3/4/5 and DPB1: stem cell donors or cord blood units that have DNA data for DRB3/4/5 and/or DPB1 are ranked somewhat higher than donors or units that do not have this additional information. CRF028 WHO HLA Nomenclature: we keep on contacting the remaining registries mentioned above to migrate their data to the new nomenclature. CRF029 NIMA match program: the request to include the Non-Inherited Maternal Antigens (NIMA) information of cord blood units to the BMDW database was investigated in A prototype of the cord blood match was prepared, and the BMDW Office sent a questionnaire to all participating cord blood banks to enquire how many banks would be able and willing to provide maternal HLA information to BMDW. A proposal to extend the BMDW file format for data delivery was discussed and approved. 1) Available on the BMDW website, in the Downloads section

25 page 21 Registry / third party support and other topics: In 2011 the BMDW Office sent one NewsBites news letter to all BMDW users (including all registries and cord blood banks), containing general information about BMDW but also details about the change requests and updates being implemented in BMDW. The many organisational changes in registries and cord blood banks (as mentioned in chapter 2) such as coordinating the merger of the Polish registries, resulted in more support hours to make sure that no data was duplicated or missing in the database. 6.2 Use of BMDW On-line services At the end of 2011 exactly 782 users were authorized to access the on-line services of BMDW (Figure 19). Transplant centre users remain the most active users of BMDW. In Figure 20 the monthly usage of the BMDW online match programs for 2011 is given. There is still an increase in the average number of matches per month, as done by users of BMDW, resulting in an increase of 12% in the total number of matches run in 2011 (compared to 2010). Figure 19 The users of online services In total: 782 Registry users 26% 74% Transplant Centre users Figure 20 The monthly usage of new BMDW online match programs in 2011 Number of match runs Cord Blood Match Program Mismatch Program Regular Match Program Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Month

26 page 22 Figure 21 Usage of BMDW online match programs per year Number of match runs ,530 23, ,516 6,590 10,140 7,904 8,413 7,752 10,523 12,552 13,663 11,209 12,156 15,695 19,064 21,716 11,277 10,668 12,744 21,997 14,946 20,344 17,767 19,826 26, ,354 4,620 2,713 8,269 2,573 11,543 10,655 20,154 32,295 40,072 41,000 41,378 48,830 59,675 59,054 59, , , , , Year Cord Blood Match Program Mismatch Program Regular Match Program

27 page 23 7Board and Staff Editorial Board The 109 participating stem cell donor registries and cord blood banks/registries (see Table 1 and 2) Chairman of the Editorial Board Machteld Oudshoorn, PhD. (from January 2011) Office Renée J.H. Bouwens-van der Klaauw Staff Carine J. Mijnarends, MSc, Managing Director Atjan J. Hop, Finance Jack N.A. Bakker, MSc, IT Angelo E.E.A. Melis, BSc, IT Leo J. Ebeling, MD, Consultant

28 page 24 8Advisory Committee Dennis L. Confer, MD (chair) Paul A. Costeas, PhD Torstein Egeland, MD, PhD Evelyne Marry, MD Carlheinz Müller, MD, PhD Cristina Navarrete, PhD Jeremy Chapman, MD Edward K.L. Yang, Associate Professor

29 page 25 9References 9.1 Publications Bochtler, W., Maiers, M., Bakker, J.N.A., Oudshoorn, M., Marsh, S.G.E., Baier, D., Hurley, C.K. & Müller, C.R. (on behalf of the information Technology Working Group of the WMDA) (2011) World Marrow Donor Association framework for the implementation of an HLA matching program in hematopoietic stem cell donor registries and cord blood banks. Bone Marrow Transplant. 46 (3): Abstracts Rocha, V., Purtill, D., Zhang, M., Spellman, S., Ruggen, A., Prasad, V., Navarrete, C., Koegler, G., Baudoux, E., Lecchi, L., Baxter-Lowe, L.A., Horowitz, M, van Rood, J.J., Kurtzberg, J., Gluckman, E. & Eapen. M. Impact of matching at-non-inherited maternal antigens on outcomes after 5/6 or 4/6 HLA mismatched unrelated cord blood transplantation for malignant haematological diseases. A matched pair analysis on behalf of Eurocord, Netcord, NMDP, IBMTR. 37th Annual EBMT Meeting, Paris, France, April 3-6, Bone Marrow Transplant. 46, suppl. 1: O115, S2, Gragert, L., Williams, E., Madbouly, A., Maiers, M. & Oudshoorn, M. High-resolution HLA-A-B-DRB1 haplotype frequencies for BMDW registries. 25th European Immunogenetics and Histocompatibility Conference (EFI), Prague, Czech Republic, May 4-7, 2011 Tissue Antigens 77 (5): P34: Invited Lectures / poster Oudshoorn, M.: Congratulation Words and Bone Marrow Donors Worldwide (BMDW) and the World Marrow Donor Association (WMDA): two global organizations for stem cell donor registries and cord blood banks Annual Conference of the China Marrow Donor Program (CMDP), Beijing, China, May 16-17, Jöris, M.M., Bierings, M., Egeler, R.M., Claas, F.H.J., van Rood, J.J. & Oudshoorn, M. Access to allogeneic hematopoietic stem cell transplantation in The Netherlands for pediatric patients with MDS and AML in first relapse treated according to protocols of the Dutch Childhood Oncology Group. (POSTER) 37th Annual EBMT Meeting, Paris, France, April 3-6, Bone Marrow Transplant. 46, suppl. 1: P1125, S352, 2011.

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