kidney kidney-pancreas pancreas liver heart lung intestine 521 173 118 236 206 99 16 28,953 1,014...
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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
90,976
28,421
878
Organ Centers 2008 Total
Worldwide Transplant Directory
Clinical Transplants 2008
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 UniversityUniv of Cincinnati College
Thomas E Starzl Inst
The Toronto Hospital
Univ Hosp, Leiden
Survyrs Hospital
Longest Surviving Transplants-2008
Clinical Transplants 2008
1991-19951996-20002001-2005
N37,32738,37742,070
T1/2
89
10
P<0.001
Deceased donor Kidney Graft Survival by Era
63
44
25
Cecka, Clinical Transplants 2008, p. 2
Cecka, Clinical Transplants 2008, p. 2
Age demographics of DD recipients with time
19-50
51-65
>65
<19
1991-19951996-20002001-2005
N13,99221,63130,231
T1/2
12.414.717.5
Cecka, Clinical Transplants 2008, p. 3
Living donor Kidney Graft Survival by Era
81
59
39
Cecka, Clinical Transplants 2008, p. 4
SiblingOffspring
ParentSpouse
Unrelated
Living Donor Relationships
HLA-ID1-haplo2-haplo
N4,665
25,75616,656
T1/2
26.714.815.1
Cecka, Clinical Transplants 2008, p. 7
HLA compatibility effect on Living donor GS
74
5857
0MM1-4MM5-6MM
N11,83241,32723,609
T1/2
11.69.68.6
HLA-ABDR
P<0.001
Cecka, Clinical Transplants 2008, p. 7
51
4439
Living donorDeceased donor
N2,375
71,686
Number of Liver Transplants in Adult donor
Goh, Clinical Transplants 2008, p. 20
Number of Liver Transplants in Pediatric donor
Goh, Clinical Transplants 2008, p. 20
Living donorDeceased donor
N1,1458,844
Liver graft survival by MELD/PELD scores
Goh, Clinical Transplants 2008, p. 29
76%
84%
70%
59%
0
25
50
75
100
Pe
rce
nt
Gra
ft S
urv
iva
l
0 2 4 6 8 10 12
Months after Transplant
1-year
0 1 2 3 4 5
Years after Transplant
5-year
p < 0.001
84
76
70
59p < 0.001
Graft survival in recipientswith Hepatocellular Carcinoma
Goh, Clinical Transplants 2008, p. 29
Years after Transplantation
49%
54%
0
25
50
75
100
Per
cen
t G
raft
Su
rviv
al
0 1 2 3 4 5 0 1 2 3 4 5
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
p<0.000110
20
30
40
50
60
70
80
90
100P
erce
nt
All
og
raft
Su
rviv
al
0 1 2 3 4 5 6 7
Years after Transplantation
2000 -20081995-19991988-1994
N17,41411,73214,760
Everly, Clinical Transplants 2008, p. 38
Heart Allograft survival by transplant Era
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
100P
erce
nt A
llogr
aft
Sur
viva
l
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years after Transplantation
Everly, Clinical Transplants 2008, p. 39
Heart Allograft survival by Recip AGE group
Everly, Clinical Transplants 2008, p. 40
PRA<50% (n=8,273)
PRA>50% (n=9,141)
Log-rank p=NS10
20
30
40
50
60
70
80
90
100P
erce
nt
All
og
raft
Su
rviv
al
0 1 2 3 4 5Years after Transplantation
Heart Allograft survival by PRA
Patient survival for primary deceased donor PAK2004-2008
LivingDeceased
N795327
1 yr (%)97.294.3
Gruessner & Sutherland, Clinical Transplants 2008, p.52
SPKPAKPTA
N42001136
491
1 yr (%)84.978.678.9
Pancreas graft function primary deceased donor2004-2008
Gruessner & Sutherland, Clinical Transplants 2008, p.52
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
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
Unadjusted Deceased Donor Graft Survivalfor First and Second Liver Transplants,
2002–2007
Source: SRTR analysis, Jan 2009
Rao & Ojo, Clinical Transplants 2008, p.65
Unadjusted Deceased Donor Graft Survival
for First and Second Heart Transplants, 2002–2007
Source: SRTR analysis, Jan 2009Rao & Ojo, Clinical Transplants 2008, p.65
Unadjusted Deceased Donor Graft Survivalfor First and Second Lung Transplants, 2002–
2007
Source: SRTR analysis, Jan 2009
Rao & Ojo, Clinical Transplants 2008, p.65
Survival (95% CI) N %Live 89.3 (88.1 – 90.4) 4502
DBD 82.1 (81.3 – 82.9) 11539DCD 81.5 (78.1 – 84.4) 1281
Graft survival for kidney only transplants in the UK,
1998 to 2007
P<0.001
% G
raft
Su
rviv
al
40
50
60
70
80
90
100
Years Posttransplant0 1 2 3 4 5
Johnson, et al. Clinical Transplants 2008, p.85
Pregnancies in female transplant recipients reported to the NTPR
Organ Recipients Pregnancies Outcomes*
Kidney 834 1301 1339
Liver 143 247 251
Liver-Kidney 4 6 7
Pancreas-Kidney 43 76 78
Pancreas alone 1 4 5
Heart 48 82 83
Heart-Lung 4 4 4
Lung 17 23 25
Totals 1094 1743 1792* Includes twins and tripletsAs of January 2009 Coscia, Armenti, et al. Clinical Transplants 2008, p.89
Pregnancies fathered by male transplant recipients reported to the NTPR
Organ Recipients Fathered Pregnancies
Outcomes*
Kidney 571 850 864
Liver 60 89 94
Liver-Kidney 2 4 4
Pancreas-Kidney 33 39 40
Heart 102 139 142
Heart-Lung 1 2 2
Heart-Lung-Kidney 1 2 2
Lung 3 3 3
Totals 773 1128 1151* Includes twins and tripletsAs of Jan 2009 Coscia, Armenti, et al. Clinical Transplants 2008, p.90
DQ2
SCr
Zhu, Terasaki, et al. Clinical Transplants 2008, p.175
Ascending strength of antibodies in graft-failure patients
DQ7
DQ2
B8
DR7SCr
Donor : A11,-, B8,49, DR7,17, DQ2,7Recipient: 2,A11,B38,60, DR4,14,DQ5,8DSA: B8, DR7, DQ2, DQ7
Zhu, Terasaki, et al. Clinical Transplants 2008, p.179
Combined strength of antibodies in graft-failure patients
Zhu, Terasaki, et al. Clinical Transplants 2008, p.184
Time to de novo antibody among all patients
A B C DRB1 DRB345 DQ
PT 2 24 56 40 1 7 10 15 51 - 1 -
DN 24 33 18 40 1 12 10 15 51 - 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
A B C DRB1 DRB345 DQ
PT 24 68 7 35 4 12 14 15 51 52 1 -
DN 24 1 51 7 12 16 13 15 51 52 1 4
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
50
100
150
200
250
300
350
A3101 A3303 A3301 B5801
Rea
ctio
n st
reng
th
Single Antigen Beads Specificities
Intact antigens Dissociated antigens
73I
Heavy chainHeavy chain
β2
Pep
tide
Intactclass I antigen
Dissociatedclass I antigen
HundredsSerum 316
71 73 74A*01011 S T DA*31012 S I DA*3301 S I DA*3303 S I DB*5801 A T Y
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
20
40
60
80
100
120
140
160
180
200
B5501 B8101 B8201 B4201 B0702 B6701 B5601 B5401 B0801
Rea
ctio
n st
reng
th
Hundreds
Single Antigen Beads Specificities
Serum 96Intact antigens Dissociated antigens
70Q
66I
Pep
tide
Intactclass I antigen
Dissociatedclass I antigen
Heavy chainβ
2 Heavy chain
66 70B*07021 I QB*07021 I QB*4201 I QB*5401 I QB*5502 I QB*5501 I QB*5601 I QB*67011 I QB*8101 I QB*8201 I QB*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
10
20
30
40
50
CW*1701 CW*0602 CW*0403 CW*1802 CW*0702
Hundreds
Intact antigens Dissociated antigens
Single Antigen Beads Specificities
Intactclass I antigen
Dissociatedclass I antigen
77N
73AP
epti
de
Heavy chain
β2
Heavy chain
Rea
ctio
n st
reng
thMI-CB 32
73 77Cw*010201 T SCw*040101 A NCw*060201 A NCw*1701 A NCw*1802 A NCw*070201 A S
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
B*5401 Epitopes (detected number)
Distance (angstrom )
Amino acid position Amino Acid# of aa
min max
0204PA 2 13 13 43 69 PA
0205PAE 3 11 19 43 69 76 PAE
0302QIA 3 4 7 65 66 69 QIA
0303QIAQ(3) 4 4 7 65 66 69 70 QIAQ
Immunogen
Number of mismatched
pairsNumber of allo-sera
Antibody production rate (%)
Total number of epitopes
Kind of epitopes
B*5401 6 4 66.7% 6 4
Immunogenic amino acids positions for B*54 antibody production
43 65 66 69 70 76
P Q I A Q E
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
Immunogen
Number of mismatched
pairsNumber of allo-sera
Antibody production
rate
Total number of epitopes
Kind of epitopes
A*2601 14 4 28.6% 11 9
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
43 62 65 66 70 73 76 77 80 90 144 145 149 163 166 167 184 207
Q R R N H T A N T D Q R T R E W A S
Maruya, Terasaki, et al. Clinical Transplants 2008, p.221
A*2601 Epitopes (detected number)
Distance ( angstrom )
Amino acid positionAmino Acids# of
aamin max
0603QRT (3) 3 4 9 144 145 149 QRT
0607REW 3 4 6 163 166 167 REW
0202QR 2 13 13 43 62 QR
0304RNH 3 4 4 65 66 70 RNH
0309TAN 3 4 6 73 76 77 TAN
0310ANT 3 4 6 76 77 80 ANT
0102D 1 90 D
0801AS 2 7 7 184 207 AS
0606R 1 163 R
Patient 1
25/M Tx: 3/7/08
Idica, Terasaki, et al. Clinical Transplants 2008, p.231
PT 3 26 8 35 4 7 17 8 3 - 52 - 6 -DN 1 3 57 35 12 15 7 8 3 - - - 4 6
A B C DRB1 DQ DRB345 Bw
Effective removal of donor-specific HLA antibody with Bortezomib
Patient 8
30/M Tx: 6/20/08
Idica, Terasaki, et al. Clinical Transplants 2008, p.234
PT 24(9) 10 40 44(12) 7 15 4 11 1 - 52 - 4 6
DN 2 32 51(5) 40 2 7 10 12 1 3 52 - 4 6
BwA B C DRB1 DQ DRB345
Effective removal of donor-specific HLA antibody with Bortezomib
Gra
ft S
urv
iva
l (%
)Deceased Donor Transplants
0%
20%
40%
60%
80%
100%
0 2 4 6 8 10 12 14Years after Transplant
Lentine, et al. Clinical Transplants 2008, p.262
T-neg, B-neg (reference)B-pos, T-negB-not measurable, T-negT-pos, B-positiveT-positive, B-not measurableUndifferentiated-negativeUndifferentiated-positive
Living Donor Transplants
0%
20%
40%
60%
80%
100%
0 2 4 6 8 10 12 14Years after Transplant
T-neg, B-neg (reference)B-pos, T-negB-not measurable, T-negT-pos, B-positiveT-positive, B-not measurableUndifferentiated-negativeUndifferentiated-positive
Lentine, et al. Clinical Transplants 2008, p.262
Gra
ft S
urv
iva
l (%
)
5 pioneers in History of Transplantation
David H. SachsRobert A. Good Ben Cosimi
Jean-Michel Dubernard
Herman Waldmann