Outcome of Unrelated HSCT in Patients Lacking HLA Matched Related Donors: Iranian Stem Cell Donor Program (ISCDP)

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1 Outcome of Unrelated HSCT in Patients Lacking HLA Matched Related Donors: Iranian Stem Cell Donor Program (ISCDP) October 18, th Congress of APBMT, Hangzhou, China AMIR ALI HAMIDIEH, MD Iranian Stem Cell Donor Program (ISCDP) Hematology, Oncology and Stem Cell Transplantation Research Center

2 Number of Transplants Worldwide Growth and Development of HSCT 40,000 35,000 Allogeneic Autologous 30,000 25,000 20,000 15,000 10,000 5, Year Annual Numbers of HSCT Worldwide

3 Current Annual Activity Estimates Worldwide Autologous transplants exceed 27,000 Allogeneic transplants exceed 22,000 More than half of allogeneic transplants use unrelated donor products More than 23 million adult donors are registered worldwide

4 EBMT Activity : Changes in stem cell source 100 auto PB 80 allo PB % cord Year

5 Differences in transplant rates on a global level Why?

6 DONOR AVAILABILITY IS A PROBLEM Unrelated Donor 40% Sibling Donor 25% Without Donor 35%

7 Alternatives to HLAmatched Related Donors NO HLA identical sibling or other relatives 10 /10 allele HLA matched unrelated donor NO HLA matched unrelated donor Unrelated Cord Blood Haploidentical Donor

8 Why Are Bone Marrow Donors Needed? There are over 16,000 people around the world who are waiting for a matching donor who could save their life. Every 5 minutes someone is diagnosed with blood cancer and every 10 minutes, blood cancer takes a precious life. Many could be saved by a bone marrow transplant

9 Why Are Bone Marrow Donors Needed? Expected increase in deaths from cancer over the next 15 years by economic system and in various regions and countries World 104% Established market economy 26% Former socialist economy 53% Latin American and Caribbean China Sub-Saharan Africa Other parts of Asia and islands India 144% 145% 149% 154% 158% Eastern Mediterranean Region 181% 0% 50% 100% 150% 200% Rastogi et al, Nature Reviews Cancer 2004

10 Why Are Bone Marrow Donors Needed? 70% of patients depend on a complete stranger; they need you to be the one to give them a second chance at life. Patients are most likely to match donors of their same race and ethnicity. Minorities are underrepresented in the national registry.

11 Bone Marrow Donors Registries Worldwide 73 stem cell donor registries in 52 countries 47 cord blood banks in 32 countries

12 Bone Marrow Donors Registries Worldwide The current number of donors and cord blood units in the BMDW database is: (23,960,724 donors and 611,607 CBU's) last updated: August 2014 There are currently 891 users from 535 organisations authorized to access the on-line BMDW services.

13 Worldwide Trends in Stem Cell Transplantation

14 Survival at 1 Year Survivals over Time: Unrelated vs. Related Donors 80% 70% 60% 50% 40% 30% 20% 10% Adjusted Survival Sibling Donor 0%

15 USAGE OF BMDW ONLINE MATCH PER YEAR 100,000 Number of match runs Cord Blood Match Program 80,000 Mismatch Program Regular Match Program 15,695 19,064 21,716 21,997 60,000 7,904 8,413 7,752 11,209 12,156 11,277 10,668 12,744 14,946 40,000 7,516 6,590 10,140 10,523 12,552 13,663 20, ,543 4,620 8,269 20, ,354 32,295 40,072 41,000 41,378 48,830 59,675 59,054 59,767 60,199 10, ,713 2,

16 Race / Ethnicity For equivalent degrees of match, transplantation between individuals of the same race/ethnicity does not improve survival.

17 IRANIAN Scenario Cases of leukemia will increase by almost 77% by 2020 More than 300 new thalassemia major patients detected annually Iranian Population of over 75 million!!

18 International Marrow Donor Registries Worldwide >23,000,000 donors USA >9,000,000, Germany >5,000,000 donors Iranian origin? Lengthy URD searches: 2 to 3 months Extreme paucity of donors of Iranian origin in western registries! HLA allele level matching further limits access

19 Need for National Donor Registries Cost of importing stem cells from other registries to Iran $ 30,000 $ 40,000 each Cost of one MUD transplant in USA >$ 5,00,000

20 Iranian Stem Cell Donor Program Hematology-Oncology and Stem Cell Transplantation Research Center Web:

21 Iranian Stem Cell Donor Program ISCDP as the first HLA registry in the East Mediterranean region has established since 2008 at Hematology-Oncology and SCT Research Center Listed under Bone Marrow Donors Worldwide (BMDW) since 2010.

22 ISCDP: First HLA Registry in Eastern Mediterranean Region 24,572,331 (23,960,724 donors and 611,607 CBU's)

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24 Number of Donors Recruited & HLA typed Total Number of donors: HLA typed (A,B & DR): 3035

25 Iranian Stem Cell Donor Program ISCDP Recruitment (All Volunteers) Volunteers HLA Typing

26 Iranian Stem Cell Donor Program

27 Pilot Project Results Profile of Blood & Marrow Stem Cell Donors- Males: 54% Female: 46% Age median: 33 years old Range: 18-57years From all over Iran & represent different Iranian ethnic populations

28 Pilot Project Results Total Search: 3867 National Search: 2550 International Search:1317 Donations from our donors for national patients : 7 Shipment for patients treated in our country : 32 (From Germany,USA,UK,Italy India) Shipment for international patients : 1 (To France)

29 Patients and Methods Search for finding unrelated donor in national and international registries were performed in 3867 patients High resolution typing for class I and II alleles was done for recipient/donor pairs in cases who had potentially unrelated donor.

30 Patients and Methods Majority of patient received BU/CY conditioning regimen. All patients were prepared for transplantation with ATG. Most common GvHD prophylaxis regimens used cyclosporin +/- methotrexate.

31 Diseases 87 patients with AML (n=23), ALL (n=17), PID (n=17), IEM (n=10), Fanconi anemia (n=9), Severe aplastic anemia (n=3), Thalassemia major (n=3), Diamond-Blackfan Anemia (n=2), FEL(n=1), MDS (n=1) NHL (n=1) transplanted using unrelated donor.

32 Patient Characteristics The median of age was 7 years (range: <1-53). 57 of patients were male.

33 Source of stem cell The source of stem cell were cord blood (n=44) peripheral blood (n=36) bone marrow (n=7)

34 Donor Characteristics Patients underwent transplant from HLA-matched unrelated donors (n=44) 1-or 2-antigen mismatched donors (n=43) Donor Sex Female (51.0%) Male (49.0%)

35 Results Median time of ANC engraftment was 16 (range=10-44) days platlete engraftment was 25 (range 13-61) days

36 Results 2-year overall survival was 52.9%(SE:6.8%) 2-year disease free survival was 44.9 %(SE:7.4%)

37 Results There were significant differences in OS and DFS according to source of stem cell (P.value=0.154, 0.02). The results of transplant were worse in cord blood group compare with peripheral blood and bone marrow group.

38 Results

39 GvHD Acute GvHD grade III-IV occurred in 13 patients Only one patient has experienced chronic extended GvHD.

40 Causes of Death Main cause of death was infection (n=10, 30.3%). Infection Relapse/progression/persistent GvHD ARDS ICH Other tx related cause

41 Discussion Since the establishment of ISCDP, the possibility of International and national search is provided for all Iranian patients requiring transplantation who do not have a related

42 Discussion To increase the chances of finding a suitable donor especially with better HLA matching, greater investment in large-scale banking is needed to increase HLA diversity.

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44 Iranian Stem Cell Donor Program Amir Ali Hamidieh Mohammadreza Ostadali Soraya Moomivand Nasrin Mehdizadeh Mahdi Jalili Maryam Behfar Arash Jalali Kamran Alimoghaddam Ardeshir Ghavamzadeh

45 The more donors who register, The more lives can be saved.

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