International Islet Transplant Registry (ITR) Newsletter #9, June 2001 Third Medical Department, University Hospital Giessen, Germany Mathias D. Brendel,

International Islet Transplant Registry (ITR)Newsletter #9, June 2001

Third Medical Department, University Hospital Giessen, Germany

Mathias D. Brendel, Bernhard J. Hering,Andreas O. Schultz, Reinhard G. Bretzel

Longest Graft Functionof Islet Allografts in Diabetes Mellitus

graft function insulin independence

IAK > 11 yrs 1 mo 4 yrs 2 m

SIK > 10 yrs 1 mo 5 yrs 10 m

PIDM-Allo 4 yrs 8 m 4 yrs 8 m

PIDM-Auto > 13 yrs > 13 yrs

B

B BB B

B B B BB B B

B

J J J J J J J J J J J J J

H

HH

H H

HH H

H HH H

H

0 1 2 3 4 5 6 7 8 9 10 11 120

102030405060708090

100

B PIDM-Auto 1990-99 (n=57)*

J Type-1-DM-Allo 1990-99 (n=237*)

H PIDM-Auto 1990-99 (n=21)*

Insulin Independence Following Islet Transplantation in ManA Comparison of Different Recipient Categories

* only well documented patients

[%]47%

9%

71%

≥ 300,000 IEQ

Summary of Adult Islet Autografts According to Institution and Year 1990 through December 31, 2000

2000 data on file incomplete

Institution Year of Transplantation(Transplantation/Isolation) 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 Σ

1. Minneapolis 3 1 2 4 12 8 6 6 12 - - 542. Leicester - - - - 1 8 7 4 3 6 5 343. Geneva - - 2 2 1 4 - - 3 - 2 144. Indianapolis - - - - - - - 4 7 - - 115. Pittsburgh - 2 1 - - 1 1 - - - - 56. Rostock - - - - - - - - 2 - 1 37. Barcelona - - - - - - - 2 - - - 28. Charlotte - - - - - 1 - - - 1 - 29. /Gent Brussels - - - - - - - - - - 1 110. /Gent Giessen - - - 1 - - - - - - - 111. / ( )Besancon Geneva Gragil - - - - - - - 1 - - - 112. Kobe - - - - - - - - - 1 - 113. ( - )Los Angeles UCLA VA - - - - - 1 - - - - - 114. Paris - 1 - - - - - - - - - 115. Zurich - - - - - - - - - - 1 1

Σ 3 4 5 7 14 23 14 17 27 8 10 132

1990:Total number of Cases through 108

Σ 240

• Institutions Minneapolis 54Leicester 34Geneva 14Indianapolis 1111 other Institutions 27

• No. of cases 140• Insulin-independent ≥ 7 days (1990-2000): 41 / 64* (64%)• Insulin-independent at ≥ 1 yr

(1990-1999 + one year follow-up): 27 / 57* (47%)if more than 300,000 IEQ transplanted: 15 / 21* (71%)

• Longest insulin-independence follow-up after total pancreatectomy: > 13 yrs

Islet Autografts from 1990 - 2000


* only well documented cases

Summary of Adult Islet Allografts According to Institution and Year - 1990 through December 31, 2000



1. Giessen - - 1 5 5 12 11 17 6 4 5 662. Milan 4 3 3 4 4 4 1 - 5 5 10 433. Miami 4 2 1 1 3 9 5 2 3 5 7 424. Pittsburgh 17 6 4 3 4 3 1 - - - - 385. Minneapolis 1 4 5 5 2 10 5 1 - - 3 366. Edmonton 2 - 1 - 1 1 - - - 5 10 207. Geneva - - - - 1 - 4 2 4 5 4 208. . St Louis 3 3 2 4 2 - - - - - - 149. Brussels - - - - 1 3 3 3 ? ? ? 10

10. Indianapolis - - - - - - 4 5 1 - - 1011. Oxford - 1 1 1 1 3 - 1 1 - - 912. ( - )Los Angeles UCLA VA - - 3 - - - 3 2 - - - 813. Madrid - - 2 1 1 2 2 - - - - 814. / ( - )San Francisco LA UCLA VA - - - 1 1 3 - - - 2 - 715. /Stockholm Giessen - - - - - - 2 2 1 2 - 716. / ( )Grenoble Geneva Gragil - - - - - - - - - 2 3 517. /Odense Milan - - - - - 5 - - - - - 518. Paris 3 1 - - - 1 - - - - - 519. Buenos Aires - - - - - 1 1 2 - - - 420. ( )/ . London Ontario St Louis 2 1 1 - - - - - - - - 421. Perugia 1 1 - - 2 - - - - - - 422. /Innsbruck Milan - - - - - 2 1 - - - - 323. Leicester - 2 1 - - - - - - - - 324. Lille - - - - - - - - 1 1 1 325. Charlestown - 2 - - - - - - - - - 226. ( )Lyon Gragil - - - - - - - - - - 2 227. Nantes - - - - - - 1 - - 1 - 228. ( )Strasbourg Gragil - - - - - - - - - 1 1 229. / Berlin RV Giessen - - - - - - - - - - 1 130. ( )Bethesda NIH - - - - - - - - - - 1 131. ( )Chicago NWH - - - - - - 1 - - - - 132. Chicago University - - - - - - - - - - 1 133. Harvard - - - - - - - - - - 1 134. Homburg - - - 1 - - - - - - - 135. Omaha - - - - 1 - - - - - - 136. /Padova Verona - - - 1 - - - - - - - 137. Seoul - - - - - - - - - 1 - 138. ( )Syracuse NYUM - - - - - - - 1 - - - 139. /Wuerzburg Giessen - - - 1 - - - - - - - 140. Zurich - - - - - - - - - - 1 1

Σ 37 26 25 28 29 59 45 38 22 34 51 394 1974 -1989:Total number of Adult Islet Allografts from 99

Σ 493

No. of Institutions Reporting Adult Islet Allografts in Patients with Diabetes by Year from 1974 through 2000

No. of Institutions by Year2000 data on file incomplete

1974 1980 1985 1990 1995 2000

1 12

4

2 2 21 1

4

2 2 2

5

9

111212

141415

11

8

12

15

0

5

10

15

No. of Adult Islet Allografts by Year

No. of Adult Islet Allografts in Patients with Diabetes by Year from 1974 through 2000


1974 1980 1985 1990 1995 2000

9

1

10 1011

3 26 4

14

2 4 2

12

37

26252829

59

44

38

22

34

51

0

10

20

30

40

50

60

Summary of Adult Islet Allografts in Type-1 Diabetic RecipientsAccording to Institution and Year - 1990 through Dec. 31, 2000



1. Giessen - - 1 5 5 12 11 17 6 4 5 662. Milan 4 3 2 4 4 4 1 - 5 5 10 423. Minneapolis 1 3 5 5 2 10 5 1 - - 3 354. Miami 4 2 1 1 1 6 2 - 3 5 7 325. Pittsburgh 7 5 3 3 4 3 1 - - - - 266. Edmonton 2 - 1 - 1 1 - - - 5 10 207. Geneva - - - - - - 4 2 4 5 4 198. . St Louis 3 3 2 4 2 - - - - - - 149. Brussels - - - - 1 3 3 3 ? ? ? 10

10. Indianapolis - - - - - - 4 5 1 - - 1011. Madrid - - 2 1 1 2 2 - - - - 812. Oxford - 1 1 1 1 2 - 1 1 - - 813. /Stockholm Giessen - - - - - - 2 2 1 2 - 714. / ( )Grenoble Geneva Gragil - - - - - - - - - 2 3 515. /Odense Milan - - - - - 5 - - - - - 516. / ( - )San Francisco LA UCLA VA - - - 1 1 1 - - - 2 - 517. Buenos Aires - - - - - 1 1 2 - - - 418. ( )/ . London Ontario St Louis 2 1 1 - - - - - - - - 419. Perugia 1 1 - - 2 - - - - - - 420. /Innsbruck Milano - - - - - 2 1 - - - - 321. Leicester - 2 1 - - - - - - - - 322. Lille - - - - - - - - 1 1 1 323. ( - )Los Angeles UCLA VA - - 2 - - - 1 - - - - 324. Paris 3 - - - - - - - - - - 325. ( )Lyon Gragil - - - - - - - - - - 2 226. Nantes - - - - - - 1 - - 1 - 227. / ( )Strasbourg Geneva Gragil - - - - - - - - - 1 1 228. Berlin - - - - - - - - - - 1 129. ( )Bethesda NIH - - - - - - - - - - 1 130. Charlestown - 1 - - - - - - - - - 131. ( )Chicago NWH - - - - - - 1 - - - - 132. Chicago University - - - - - - - - - - 1 133. Harvard - - - - - - - - - - 1 134. ( )Homburg Saar - - - 1 - - - - - - - 135. Omaha - - - - 1 - - - - - - 136. Seoul - - - - - - - - - 1 - 137. Zurich - - - - - - - - - - 1 1

Σ 27 22 22 26 26 52 40 33 22 34 51 355 1974 -1989:Total number of Adult Islet Allografts from 90

Σ 445

• No. of cases: 355• Institutions: Giessen 66

Milan 42Minneapolis 35Miami 32Pittsburgh 26Edmonton 20Geneva 19St. Louis 1429 additional institutions (≤ 10 cases) 99

• Insulin-independent ≥ 7 days (1990-2000): 52 / 281 (19%)*• Insulin-independent at ≥ 1 yr

(1990-1999 + one year follow-up): 27 / 237 (11%)*• Insulin-independent after 1:1 tx ≥ 7 days (1990-2000): 21 / 151 (14%)*• Insulin-independent after 1:1 tx at ≥ 1 yr

(1990-1999+ one year follow-up): 13 / 140 ( 9%)*• Longest insulin-indepence follow-up: 70 months

Adult Islet Allografts in Type-1 Diabetic Recipients 1990 - 2000

* only well documented cases

169

108133

34

76

23

Europe North-America0

50

100

150

200

Insulin Independence and Basal C-Peptide after Adult Islet Allotransplantation in 281 Type-1 Diabetic Recipients from 1990 - 2000 according to Continent

total # of cases C-peptide ≥ 0.5 ng/mL at ≥ 1mo off insulin ≥ 1 week

(79%)

(20%)

(70%)

(21%)

Four transplantations performed elsewhere

140

9795

18

78

20

single donor multiple donors0

20

40

60

80

100

120

140

160

Insulin Independence and Basal C-Peptide One Year after Adult Islet Allotransplantationin 237* pre Tx C-Peptide negative Type-1 Diabetic Recipients from

1990 - 1999 according to Number of Donors


(68%)

(13%)

(80%)

(21%)

* Only well documented cases

146

78

114

32

52

4

≥ 6000 IEQ/kg BW < 6000 IEQ/kg BW0

20

40

60

80

100

120

140

160

Insulin Independence and Basal C-Peptide One Year after Adult Islet Allotransplantation in 237* pre Tx C-Peptide negative Type-1 Diabetic Recipients

from 1990 - 1999 according to Number of Islet Equivalents per kg Body Weight


(78%)

(22%)

(67%)

no data available in 13 cases

(5%)


162

62

126

2838

7

≤ 8 hrs > 8 hrs0

20

40

60

80

100

120

140

160

180


from 1990 - 1999 according to Cold Ischemia Time

no data available in 13 cases


(78%)

(17%)(61%)

(11%)


131

87

7 93

101

14

59

23

50

5 1 3 0

SIK IAK SIL ITA others0

20

40

60

80

100

120

140


from 1990 - 1999 according to Recipient Category


(68%)

(77%)

(11%)

(26%)


147

3015

40

117

3120

315

1

18

2

ATG/ALG OKT3 Anti-IL-2R AB no T-cell AB0

20

40

60

80

100

120

140

160

Insulin Independence and Basal C-Peptide after One Year Adult Islet Allotransplantation in 237* pre Tx C-Peptide negative Type-1 Diabetic Recipients

from 1990 - 1999 according to Induction Immunosuppression


(80%)

(21%)(67%)

(10%)

(45%)(5%)

(100%) (7%)

* Only well documented cases (Five additional cases with Anti-CD4 not depicted)

67

170

58

21

115

17

all four ≥ one not0

20

40

60

80

100

120

140

160

180


from 1990 - 1999 according to Common Criteria

Common Criteria: a) IEQ/kg BW ≥ 6,000; b) CIT ≤ 8 hrs; c) ALG/ATG; d) Implantation Site: Liver (via portal vein)


(87%)

(68%)

(10%)


(31%)

B

B

B B

B B B

B B B B B B


0 1 2 3 4 5 6 7 8 9 10 11 120

10

20

30

40

50

60

70

80

90

100

months posttransplant

B Graft survival (C-peptide ≥ 0.5 ng/mL)

J Patient survival

Cumulative One-Year Patient and Graft Survival in 237* pre TxC-Peptide Negative Type-1 Diabetic Recipients (1990-1999)

[%]

96 %

41 %


J J J J J J J J J J J J J J J J J J J J J J J J J J J J J J J J J J J J JB

B

B B

B B B

B B B B B B

B B B B B B B B B B B B

B B B B B B B B B B B B

0 3 6 9 12 15 18 21 24 27 30 33 360

10

20

30

40

50

60

70

80

90

100


J Patient Survival

B Graft Survival (basal C-peptide ≥ 0.5 ng/mL)

Cumulative Three-Year Patient and Graft Survival inC-Peptide Negative Type-1 Diabetic Recipients; 1990-1997; n=200*

19 %

94 %

[%]


B

B

B B

B B B

B B B B B B


0 1 2 3 4 5 6 7 8 9 10 11 120

10

20

30

40

50

60

70

80

90

100



J Patient survival

Cumulative One-Year Patient and Graft Survival in87* pre Tx C-Peptide Negative Type -1 Diabetic Recipients (1990-1999)

Islet After Kidney (IAK) Transplantation

[%]

98 %

39 %


B

B

B B

B B B

B B B B B B


0 1 2 3 4 5 6 7 8 9 10 11 120

10

20

30

40

50

60

70

80

90

100



J Patient survival

Cumulative One-Year Patient and Graft Survival in131* pre Tx C-Peptide Negative Type-1 Diabetic Recipients (1990-1999)

Simultaneous Islet Kidney (SIK) Transplantation

[%]

96 %

47 %


H

H

H HH H H

H H H H H H

E

E E

E E E

E E E E E E E

B

B B

B B BB B B B B B B

0 1 2 3 4 5 6 7 8 9 10 11 120

10

20

30

40

50

60

70

80

90

100


H 1990-93 (n=82)

E 1994-97 (n=118)

B 1998-99 (n=37)

Cumulative One-Year Graft Survival by ERAC-Peptide Negative Type-1 Diabetic Recipients; 1990-1999; n=237*

38 %36 %

68 %

[%]


H H H H H H H H H H H H H

E E E E E E E E E E E E E

BB B

BB

B BB

BB B B

B

0 1 2 3 4 5 6 7 8 9 10 11 120

10

20

30

40

50

60

70

80

90

100


H 1990-93 (n=82)

E 1994-97 (n=118)

B 1998-99 (n=37)

One-Year Insulin Indepence by ERAC-Peptide Negative Type-1 Diabetic Recipients; 1990-1999; n=237*

14 %9 %8 %

[%]


Type-1 Diabetic Recipients of Adult Islet Allografts (One Year Follow-Up) Insulin-Independent Cases (n=50) through December 31, 1999

S=Steroids, C=Cyclosporine, T=Tacrolimus, Si=Sirolimus, D=Deoxyspergualin, A=Azathioprin, MMF=Mycophenolate Mofetil, aIL2R=Anti IL-2 Rec Ab, CPM=Cyclophosphamide, NA=Not AvailableInsulin independence for ≥ 7 days at any time after I-Tx

Case Institution Year of Tx No. of IEQ/kg No. of Donors Purity (%) Immunosuppression

1. Zurich 1978 3,864 1 1 ALG, S, A, CPM2. Paris 1988 2,143 1 80 ALG, S, C, A3. St. Louis 1989 12,582 2 95 ALG, C, A4. St. Louis 1990 14,735 3 91 ALG, S, A5. St. Louis 1993 22,055 8 93 OKT3, S, C, A6. St. Louis 1993 26,494 5 88 ALG, S, C, A7. Edmonton 1990 9,692 5 70 ALG, S, C, A8. Edmonton 1992 9,866 6 59 ALG, S, C, A9. Edmonton 1999 9,407 2 60 aIL2-R, T, Si

10. Edmonton 1999 11,138 2 60 aIL2-R, T, Si11. Edmonton 1999 13,225 2 60 aIL2-R, T, Si12. Edmonton 1999 11,800 4 60 aIL2-R, T, Si13. Edmonton 1999 13,987 2 60 aIL2-R, T, Si14. Milan 1990 10,773 1 95 ALG, S, C, A15. Milan 1990 8,610 2 75 ALG, S, C, A16. Milan 1991 16,859 3 80 ALG, S, C17. Milan 1992 11,557 2 80 ALG, S, C, A18. Milan 1994 28,995 3 63 ALG, S, C, A19. Milan 1994 14,489 1 60 ALG, S, C, A20. Milan 1995 9,601 1 50 ALG, C, A21. Milan 1998 13,750 2 65 ALG, C, MMF22. Milan 1998 NA 2 75 ALG, S, C23. Milan 1999 12,948 2 50 ALG, S, C, MMF24. Milan 1999 7,413 1 90 ALG, S, C, MMF25. Milan 1999 NA 2 65 ALG, S, C, MMF26. Miami 1990 18,669 3 47 OKT3, S, C, A27. Miami 1990 18,884 3 50 OKT3, S, C, A28. Miami 1995 15,691 1 85 ATG, S, T, MMF29. Giessen 1992 6,156 1 92 ATG, S, C30. Giessen 1995 7,246 1 95 aIL2-R, S, C31. Giessen 1995 12,031 1 90 ATG, S, C, A32. Giessen 1995 8,251 1 90 ATG, S, C, A33. Giessen 1995 6,379 1 85 ALG, S, C, A34. Giessen 1996 5,475 1 90 ALG, S, C, A35. Giessen 1996 7,777 1 98 ATG, S, C, A36. Giessen 1996 5,472 1 85 ATG, S, C, A, MMF37. Giessen 1997 6,548 1 85 ALG, S, C, A38. Giessen 1997 7,896 1 90 ATG, S, C, A39. Giessen 1997 12,636 1 70 ATG, S, C, A40. Minneapolis 1992 7,882 1 5 ALG, S, C, A, D41. Minneapolis 1992 13,319 1 5 ALG, S, C, A, D42. Minneapolis 1995 9,004 1 5 S, C, A43. Pittsburgh 1994 8,137 1 80 S, T44. Brussels 1995 4,400 6 70 S, C, A45. Brussels 1996 2,600 8 59 S, C, A46. Odense/ Milan 1995 9,360 2 80 ATG, C47. Geneva 1996 8,800 2 28 ATG, S, C, A48. Geneva 1999 19,135 1 50 aIL2-R, S, C, MMF49. Los Angeles VA 1996 NA 4 NA S, T, MMF50. Nantes 1999 9,467 2 50 ALG, S, C, MMF

Mean ± SEM 11,217±822 2.24±0.25 67.5±3.6

(1) New website for the International Islet Transplant Registry at the University of Giessen, including the newest available version of the annual newsletter provided by the ITR, and valuable links to websites:http://www.med.uni-giessen.de/itr

(2) Maintenance of the ITR will be supported by the JDFI for the coming five-year period

Last but not Least

We would like to thank all of the collaborating institutions for their continued support of the

Islet Transplant Registry

Documents

International Islet Transplant Registry (ITR) Newsletter #9, June 2001 Third Medical Department, University Hospital Giessen, Germany Mathias D. Brendel,