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Kidney Kidney-Pancreas Pancreas Liver Heart Lung Intestine 521 173 118 236 206 99 16 28,953 1,014 477 10,306 3,069 2,152 78 843,318 24,175 8,083 186,642.

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Presentation on theme: "Kidney Kidney-Pancreas Pancreas Liver Heart Lung Intestine 521 173 118 236 206 99 16 28,953 1,014 477 10,306 3,069 2,152 78 843,318 24,175 8,083 186,642."— Presentation transcript:

1 Kidney Kidney-Pancreas Pancreas Liver Heart Lung Intestine 521 173 118 236 206 99 16 28,953 1,014 477 10,306 3,069 2,152 78 843,318 24,175 8,083 186,642 90,976 28,421 878 Organ Centers2008Total Worldwide Transplant Directory Clinical Transplants 2008

2 KIDNEY Related donor Deceased donor Unrelated live donor LIVER HEART PANCREAS-KIDNEY PANCREAS LUNG BONE MARROW 46 41 37 39 30 27 26 22 41 University of Colorado Royal North Shore Hosp Univ de Sao Paulo University of Colorado Stanford University Univ of Cincinnati College Thomas E Starzl Inst The Toronto Hospital Univ Hosp, Leiden Surv yrs Hospital Longest Surviving Transplants-2008 Clinical Transplants 2008

3 1991-1995 1996-2000 2001-2005 N 37,327 38,377 42,070 T 1/2 8 9 10 P<0.001 Deceased donor Kidney Graft Survival by Era 63 44 25 Cecka, Clinical Transplants 2008, p. 2

4 Age demographics of DD recipients with time 19-50 51-65 >65 <19

5 1991-1995 1996-2000 2001-2005 N 13,992 21,631 30,231 T 1/2 12.4 14.7 17.5 Cecka, Clinical Transplants 2008, p. 3 Living donor Kidney Graft Survival by Era 81 59 39

6 Cecka, Clinical Transplants 2008, p. 4 Sibling Offspring Parent Spouse Unrelated Living Donor Relationships

7 HLA-ID 1-haplo 2-haplo N 4,665 25,756 16,656 T 1/2 26.7 14.8 15.1 Cecka, Clinical Transplants 2008, p. 7 HLA compatibility effect on Living donor GS 74 58 57

8 0MM 1-4MM 5-6MM N 11,832 41,327 23,609 T 1/2 11.6 9.6 8.6 HLA-ABDR P<0.001 Cecka, Clinical Transplants 2008, p. 7 51 44 39

9 Living donor Deceased donor N 2,375 71,686 Number of Liver Transplants in Adult donor Goh, Clinical Transplants 2008, p. 20

10 Number of Liver Transplants in Pediatric donor Goh, Clinical Transplants 2008, p. 20 Living donor Deceased donor N 1,145 8,844

11 Liver graft survival by MELD/PELD scores Goh, Clinical Transplants 2008, p. 29 76% 84% 70% 59% 0 25 50 75 100 Percent Graft Survival 024681012 Months after Transplant 1-year 012345 Years after Transplant 5-year p < 0.001 84 76 70 59 p < 0.001 MELD/PELD score <15 (n = 3,855) 15 – 22 (n = 11,294) 23 – 30 (n = 10,305) >30 (n = 5,084)

12 Graft survival in recipients with Hepatocellular Carcinoma Goh, Clinical Transplants 2008, p. 29 Years after Transplantation 49% 54% 0 25 50 75 100 Percent Graft Survival 012345012345 HCC T2 (n = 3,457) M/P score 22-30 (n = 11,294) HCC (n = 4,817) Other cancers (n = 1,048) p < 0.001 62 70 p < 0.001 49 54

13 p<0.0001 10 20 30 40 50 60 70 80 90 100 Percent Allograft Survival 01234567 Years after Transplantation 2000 -2008 1995-1999 1988-1994 N 17,414 11,732 14,760 Everly, Clinical Transplants 2008, p. 38 Heart Allograft survival by transplant Era

14 Infant, 0-1 yr (n=1,636) Pediatric, 1-18 yr (n=3,959) Elderly, 65+ yr (n=3,100) Adult, 18-65 yr (n=35,211) 10 20 30 40 50 60 70 80 90 100 Percent Allograft Survival 01234567891011121314151617181920 Years after Transplantation Everly, Clinical Transplants 2008, p. 39 Heart Allograft survival by Recip AGE group

15 Everly, Clinical Transplants 2008, p. 40 PRA<50% (n=8,273) PRA>50% (n=9,141) Log-rank p=NS 10 20 30 40 50 60 70 80 90 100 Percent Allograft Survival 012345 Years after Transplantation Heart Allograft survival by PRA

16 Patient survival for primary deceased donor PAK 2004-2008 Living Deceased N 795 327 1 yr (%) 97.2 94.3 Gruessner & Sutherland, Clinical Transplants 2008, p.52

17 SPK PAK PTA N 4200 1136 491 1 yr (%) 84.9 78.6 78.9 Pancreas graft function primary deceased donor 2004-2008 Gruessner & Sutherland, Clinical Transplants 2008, p.52

18 Number of Repeat Transplants, by Organ 1990–2007* Source: SRTR analysis, Jan 2009 *Includes living and deceased donors Kidney Liver Heart Lung Rao & Ojo, Clinical Transplants 2008, p.60

19 Unadjusted Living and Deceased Donor Graft Survival for First and Second Kidney Transplants, 2002–2007 Source: SRTR analysis, Jan 2009 Rao & Ojo, Clinical Transplants 2008, p.64

20 Unadjusted Deceased Donor Graft Survival for First and Second Liver Transplants, 2002–2007 Source: SRTR analysis, Jan 2009 Rao & Ojo, Clinical Transplants 2008, p.65

21 Unadjusted Deceased Donor Graft Survival for First and Second Heart Transplants, 2002–2007 Source: SRTR analysis, Jan 2009 Rao & Ojo, Clinical Transplants 2008, p.65

22 Unadjusted Deceased Donor Graft Survival for First and Second Lung Transplants, 2002–2007 Source: SRTR analysis, Jan 2009 Rao & Ojo, Clinical Transplants 2008, p.65

23 Survival (95% CI) N % Live 89.3 (88.1 – 90.4) 4502 DBD 82.1 (81.3 – 82.9) 11539 DCD 81.5 (78.1 – 84.4) 1281 Graft survival for kidney only transplants in the UK, 1998 to 2007 P<0.001 % Graft Survival 40 50 60 70 80 90 100 Years Posttransplant 012345 Johnson, et al. Clinical Transplants 2008, p.85

24 Pregnancies in female transplant recipients reported to the NTPR OrganRecipientsPregnanciesOutcomes* Kidney83413011339 Liver143247251 Liver-Kidney467 Pancreas-Kidney437678 Pancreas alone145 Heart488283 Heart-Lung444 Lung172325 Totals109417431792 * Includes twins and triplets As of January 2009 Coscia, Armenti, et al. Clinical Transplants 2008, p.89

25 Pregnancies fathered by male transplant recipients reported to the NTPR OrganRecipientsFathered Pregnancies Outcomes* Kidney571850864 Liver608994 Liver-Kidney244 Pancreas-Kidney333940 Heart102139142 Heart-Lung122 Heart-Lung-Kidney122 Lung333 Totals77311281151 * Includes twins and triplets As of Jan 2009 Coscia, Armenti, et al. Clinical Transplants 2008, p.90

26 DQ2 SCr Zhu, Terasaki, et al. Clinical Transplants 2008, p.175 Ascending strength of antibodies in graft-failure patients

27 DQ7 DQ2 B8 DR7 SCr Donor : A11,-, B8,49, DR7,17, DQ2,7 Recipient: 2,A11,B38,60, DR4,14,DQ5,8 DSA: B8, DR7, DQ2, DQ7 Zhu, Terasaki, et al. Clinical Transplants 2008, p.179 Combined strength of antibodies in graft-failure patients

28 Zhu, Terasaki, et al. Clinical Transplants 2008, p.184 Time to de novo antibody among all patients

29 ABCDRB1DRB345DQ PT 224564017101551-1- DN 24331840112101551-1- CD52, 27/M, Tx: 5/12/08 Kaneku, Terasaki, et al. Clinical Transplants 2008, p.193 Clonal deletion with no post-tx maintenance for 2 months

30 ABCDRB1DRB345DQ PT 2468735412141551521- DN 24151712161315515214 CD15, 35/M, Tx: 4/16/08 Kaneku, Terasaki, et al. Clinical Transplants 2008, p.194 Clonal deletion with no post-tx maintenance For 3.5 months

31 50 100 150 200 250 300 350 A3101A3303A3301B5801 Reaction strength Single Antigen Beads Specificities Intact antigensDissociated antigens 73I Heavy chain β2β2 Peptide Intact class I antigen Dissociated class I antigen Hundreds Serum 316 717374 A*01011STD A*31012S I D A*3301S I D A*3303S I D B*5801ATY aa & position El-Awar, Terasaki, et al. Clinical Transplants 2008, p.206 Reactivity of anti HLA A-locus alloantibody with intact and dissociated antigens on the SA beads

32 20 40 60 80 100 120 140 160 180 200 B5501B8101B8201B4201B0702B6701B5601B5401B0801 Reaction strength Hundreds Single Antigen Beads Specificities Serum 96 Intact antigensDissociated antigens 70Q 66I Peptide Intact class I antigen Dissociated class I antigen Heavy chain β2β2 6670 B*07021IQ IQ B*4201 I Q B*5401IQ B*5502 I Q B*5501 I Q B*5601IQ B*67011 I Q B*8101IQ B*8201IQ B*0801 I N aa & position El-Awar, Terasaki, et al. Clinical Transplants 2008, p.208 Reactivity of anti HLA B-locus alloantibody with intact and dissociated antigens on the SA beads

33 10 20 30 40 50 CW*1701CW*0602CW*0403CW*1802CW*0702 Hundreds Intact antigensDissociated antigens Single Antigen Beads Specificities Intact class I antigen Dissociated class I antigen 77N 73A Peptide Heavy chain β2β2 Reaction strength MI-CB 32 7377 Cw*010201TS Cw*040101AN Cw*060201AN Cw*1701AN Cw*1802AN Cw*070201AS aa & position El-Awar, Terasaki, et al. Clinical Transplants 2008, p.209 Reactivity of anti HLA C-locus alloantibody with intact and dissociated antigens on the SA beads

34 B*5401 Epitopes (detected number) Distance （ angstrom ） Amino acid positionAmino Acid # of aa minmax 0204PA 213 4369 PA 0205PAE 31119436976 PAE 0302QIA 347656669 QIA 0303QIAQ(3) 44765666970QIAQ Immunogen Number of mismatched pairs Number of allo-sera Antibody production rate (%) Total number of epitopes Kind of epitopes B*54016466.7%64 Immunogenic amino acids positions for B*54 antibody production 436566697076 PQIAQE B*54 Immunogenic aa position for Ab. production Amino acid position of HLA-B*54 putative epitopes Putative epitopes of anti sera produced by HLA-B54 mismatched mothers Immunogenic aa position for HLA-B*54 mismatched pair Maruya, Terasaki, et al. Clinical Transplants 2008, p.221

35 Immunogen Number of mismatched pairs Number of allo-sera Antibody production rate Total number of epitopes Kind of epitopes A*260114428.6%119 A*2601 Immunogenic aa position for Ab. production aa position of HLA- A*2601 putative epitopes Putative epitopes of anti sera produced by HLA-A*2601, A*2602 mismatched mothers Immunogenic aa position for HLA-A*2601, A*2602 mismatched pair Immunogenic amino acids positions for A*2601 antibody production 43626566707376778090144145149163166167184207 QRRNHTANTDQRTREWAS Maruya, Terasaki, et al. Clinical Transplants 2008, p.221 A*2601 Epitopes (detected number) Distance （ angstrom ） Amino acid position Amino Acids # of aa minmax 0603QRT (3)349144145149QRT 0607REW346163166167REW 0202QR213 4362 QR 0304RNH344656670RNH 0309TAN346737677TAN 0310ANT346767780ANT 0102D1 90 D 0801AS277184207 AS 0606R1 163 R

36 Patient 1 25/M Tx: 3/7/08 Idica, Terasaki, et al. Clinical Transplants 2008, p.231 PT326835471783-52-6- DN 1 3 57 35 12 15 7 83--- 4 6 ABCDRB1DQDRB345Bw Effective removal of donor-specific HLA antibody with Bortezomib

37 Patient 8 30/M Tx: 6/20/08 Idica, Terasaki, et al. Clinical Transplants 2008, p.234 PT24(9)104044(12)7154111-52-46 DN 23251(5) 40 2 7 1012 1 3 52-46 BwABCDRB1DQDRB345 Effective removal of donor-specific HLA antibody with Bortezomib

38 Graft Survival (%) Deceased Donor Transplants Years after Transplant Lentine, et al. Clinical Transplants 2008, p.262 T-neg, B-neg (reference) B-pos, T-neg B-not measurable, T-neg T-pos, B-positive T-positive, B-not measurable Undifferentiated-negative Undifferentiated-positive

39 Living Donor Transplants Years after Transplant T-neg, B-neg (reference) B-pos, T-neg B-not measurable, T-neg T-pos, B-positive T-positive, B-not measurable Undifferentiated-negative Undifferentiated-positive Lentine, et al. Clinical Transplants 2008, p.262 Graft Survival (%)

40 5 pioneers in History of Transplantation David H. SachsRobert A. GoodBen Cosimi Jean-Michel Dubernard Herman Waldmann

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