Download pdf - INTERNATIONAL ISLET TRANSPLANT REGISTRY · OK T3 Height (cm) 1st 2nd Autograft Allograft Xenograft Species: Adult Fetal Donor Tissue ITR-R-93-1. International ISLET TRANSPLANT REGISTRY

INTERNATIONAL ISLETTRANSPLANT

REGISTRY

In this Newsletter• Introduction, Editorial Board, Registry Staff and Address.............. 2 - 3• New ITR-Forms .................................................................................... 4 - 7• Results on all adult islet allografts through Dec 31, 1992 ............... 8 - 11• Detailed analysis of the adult 1990-92 cases.................................... 12 - 19• Listing of insulin independent adult islet allograft recipients......... 20 - 21• Brief description of fetal grafts reported to the ITR.......................... 22 - 23• Listing of participating institutions.................................................... 24

New ITR-Forms developed

considering

valuable proposals

made by Dr. David Scharp,

Washington University, St. Louis,

in cooperation with other leading

North American Islet Transplant Centers

RECIPIENT FORM FOR CLINICAL ISLET TRANSPLANTS

LiverSpleenKidney CapsuleEpiploic Flap

Site of Tx

ITR Institution #

Case #

Transplant Team

Date of Tx Type of DMType-I DM

Date of Birth

Age of Diabetes Onset

Weight (kg)

Sex malefemale

0A

BAB

ABO

1No. of Donors

HLA:

Local Code

Transplant Center

A B DR

RECIPIENT DATA

TRANSPLANT DATA

INSTITUTION DATA

First and Last Initial

HLA of tx'd Kidney:

positivenegative

CMV

Induction IS

Height (cm)

AutograftAllograftXenograftSpecies:

AdultFetal

Donor Tissue

• Recipient Form for Clinical Islet Transplants

• Donor Form for Clinical Islet Transplants (Adult Tissue)

• Donor Form for Clinical Islet Transplants (Fetal Tissue)

• Follow-Up Form for Clinical Islet Transplants

D ear Islet Transplant Registry Participant,

we are pleased to present the IsletTransplant Registry Newsletter No. 4on the occasion of the 4th Internatio-nal Congress on Pancreas and IsletTransplantation in Amsterdam, June27-30, 1993. We would like to expressour gratitude to the Chairman of thisC o n g ress, Dr. Reinout van Schilf-gaarde, for offering the possibility tohand over a personal copy to eachcongress participant. In addition, wewould also like to thank you for yourcontinuous support and efforts in pro-viding us with data on your patients.

This Newsletter includes re v i s e dRegistry Forms, results of an analysison all adult islet allografts performedworldwide through Dec 31, 1992, withmain emphasis on the period fro m1990-92 as well as a brief descriptionof fetal islet grafts reported to the Regi-stry.

The significant progress of the lastyears culminating in prolonged insu-lin independence following islet allot-ransplantation in diff e rent re c i p i e n tcategories and at diff e rent instituti-ons made us expecting a rapid deve-lopment in the field of clinical islettransplantation. It is true that furthercenters reached insulin independenceafter islet transplantation but theexpected bre a k t h rough on a widefront failed to come. At present, onlyfive patients are insulin independentafter islet allotransplantation, thre etype 1 diabetic patients (two in Milan,one in Minneapolis) as well as twopatients with pancre a t e c t o m y - i n d u-ced diabetes mellitus (one patient inP i t t s b u rgh and one patient in Milan).The number of transplantations peryear decreased from 36 in 1990 to 26in 1991 and 23 in 1992. In the first sixmonths of 1993 only eight transplan-tations are known to be performed(four in Giessen, two in Milan, one inMinneapolis and another one in LosAngeles). More o v e r, the results in islettransplantation could not be signifi-cantly improved since 1990. Another

step forward is of crucial importancefor islet transplantation and for allinstitutions involved to keep clinicaland scientific programs ru n n i n g .

Which future directions are pro-mising enough to be taken? Fre-quently mentioned approaches arecollagenase, pre-transplant isletimmunomodulation and new immu-n o s u p p ressive agents etc. However,it is only through a careful analysis ofdata that the impact of these or othera p p roaches can be substantiated.

In this respect, the Islet TransplantRegistry can contribute to advance thep ro g ress. As the number of trans-planted cases per center is low, it isevident that trends or even conclusi-ons can emerge much earlier whenall results achieved worldwide arecollected and then subjected to scien-tific analysis. The Registry can onlyfulfill this task if the forms will becompleted more thoroughly and con-scientious in the future. The accuracyof the Registry´s results depends verymuch on the quality of data that youprovide and can only be guaranteedby truthful reporting of successes andfailures.

We have always realized that com-pleting the previous Registry Formswas cumbersome and time consu-ming for you. Thus, these formsunderwent major revisions in ord e rto achieve more clearness by consi-dering only the very essential items.In this respect, we very much appre-ciated the recommendations pro v i-ded by Dr. David W. Scharp,Washington University, St. Louis andcolleagues of other leading NorthAmerican Islet Transplant Centers.

We are confident that completion ofthe Forms as well as data entry willnow be simplified and accelerated. Asubstantial advantage of the newForms is that print-outs of data onceput into the data base can be genera-ted directly onto these Forms. Thisguarantees a habitual format; proof-reading and updating of the data canbe done much more efficient on a

single form. Disks with File MakerPro 2.0 - files for direct data entry ona Macintosh computer are availableon request.

Standardized and accepted criteriafor the assessment of islet preparati-ons and for patient monitoring posttransplant are urgently re q u i red. Afirst step was the definition of isletequivalents and of the Sustacal sti-mulation index by Dr. David W.Scharp. In particular, assessment ofviability and function of human isletsp retransplant should be standard i-zed. We have to face loss of islet graftfunction in about 30% of cases withinthe first month and it will there f o rebe important to determine whetherthese early graft failures are a re s u l tof grafting an insufficient number ofviable islet equivalents. Many centersalready use similar methods for isletassessment, however, a large numberof unnecessary modifications existpreventing meaningful comparisonsof results between different instituti-ons.

During the Fourth InternationalC o n g ress on Pancreas and Islet Tr a n s-plantation a Workshop chaired by Dr.R e i n h a rd G. Bretzel, University ofGiessen, and Dr. Camillo Ricordi, Uni-versity of Pittsburgh, will try againto elaborate improvements in this cru-cial field. It is to be hoped that thisWorkshop will manage to define gui-delines for islet graft assessment andpatient monitoring and that everygroup performing clinical islet trans-plantation will adhere to these gui-delines in the future, eventually incarefully designed multicenter trials.

Again, we thank for your coopera-tion and participation in the IsletTransplant Registry.

Giessen, June 1993

Bernhard J. HeringChristian C. BrowatzkiAndreas O. SchultzBarbara WatzReinhard G. BretzelKonrad Federlin

Justus-Liebig-University of GiessenDepartment of Medicine

The Islet Transplant Registry Newsletter is publishedregularly and distributed to all interested institutions.It is anticipated that the fith newsletter will be issuedtowards the end of 1993.

Konrad Federlin, MDProfessor of Medicine

Reinhard G. Bretzel, MDProfessor of Medicine

Bernhard J. Hering, MD

Professor Konrad Federlin, MDDirector

Professor Reinhard G. Bretzel, MDVice-Director

Bernhard J. Hering, MDRegistry Coordinator

Christian C. Browatzki, MDRegistry Vice-Coordinator

Andreas O. SchultzRegistry Administrator & Programmer

Barbara WatzCorrespondent

Professor David E.R. Sutherland, MD, PhDDirector, International Pancreas Transplant Registry

Kay C. Moudry-Munns, RNC, CCRN, BSNCoordinator, International Pancreas Transplant Registry

Islet-Transplant-RegistryContact: Bernhard J. Hering, MDDepartment of MedicineJustus-Liebig-University of GiessenRodthohl 6D-35392 GiessenGermanyPhone: (49)-641-702-7445Fax: (49)-641-702-7443

International

RECIPIENT FORM FOR CLINICAL ISLET TRANSPLANTS

Director: Professor Konrad Federlin, M.D.Medizinische Klinik III & Poliklinik der Justus-Liebig-Universität

Rodthohl 6, 35392 Giessen, Germany.

ISLET TRANSPLANT REGISTRY

Phone: (49)-641-702-7445, Fax:(49)-641-702-7443

LiverSpleenKidney CapsuleEpiploic FlapPeritoneal Cavityi.m.s.c._____

Site of TxRecipient Category

ITR Institution #

Case #

Transplant Team

Date of Tx Type of DMType-I DM

Date of Birth

Age of Diabetes Onset

Weight (kg)

Sex malefemale

0A

BAB

ABO

1No. of Donors

Prev. Islets

Prev. Pancreas

Last Date of Completion

HLA:

Prev. Kidney

1st2nd

Local Code

Transplant Center

A B DR DQ

RECIPIENT DATA

TRANSPLANT DATA

Dates of Previous Txof Other Organs

1st2nd3rd

INSTITUTION DATA

Comments for Recipient and Donor Data

First and Last Initial

HLA of tx'd Kidney:

A B DR DQ

positivenegative

CMV

ITAIAKSIKSILOthersWeitere…

Induction IS(all IS given peri tx)

NoneSteroidsCsAAZAFK 506DSGALS/ALG/ATGOK T3

Height (cm)

1st2nd

AutograftAllograftXenograftSpecies:

AdultFetal

Donor Tissue

ITR-R-93-1

International


DONOR FORM FOR CLINICAL ISLET TRANSPLANTS (ADULT TISSUE )



Phone: (49)-641-702-7445, Fax:(49)-641-702-7443

1

Age (yrs)malefemale

malefemale

malefemale

malefemale

malefemale

malefemale

Sex

Refer to Donor #

0A

BAB

0A

BAB

0A

BAB

0A

BAB

0A

BAB

0A

BAB

AB0

Cold Perfusion- /Storage-Solution

YesNo

YesNo

YesNo

YesNo

YesNo

YesNo

Distension Solution

Cold Ischemia (min)

Fresh CultureCryopres.






Pretreatment

Islet NumberIslet Equivalents,IEQIslet Purity (%)

Intraduct. Collag. Pre Cold Storage

HLA: ABDRDQ

DONOR DATA

Test Methods

Pancreas Procurement and Preservation

Islet Graft Preparation

INSTITUTION AND RECIPIENT IDENTIFICATION

If Cultured: DaysTemp (°C)

pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

NDCrossmatch

Pre Transplant Islet Viability Tests

Test Results

pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

NDCMV

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

Time of IEQ Count

O2 (%)

1

Case # Date of TxLocal CodeInstitution # Transplant Center

YesNo

YesNo

YesNo

YesNo

YesNo

YesNo

Cold Perfusion

ITR-DA-93-1

International


DONOR FORM FOR CLINICAL ISLET TRANSPLANTS (FETAL TISSUE )



Phone: (49)-641-702-7445, Fax:(49)-641-702-7443

malefemale

malefemale

malefemale

malefemale

malefemale

malefemale

Sex

Refer to Donor #

0A

BAB

0A

BAB

0A

BAB

0A

BAB

0A

BAB

0A

BAB

AB0

Warm Ischemia (min)

Cold Ischemia (min)







Pretreatment

HLA: ABDRDQ

DONOR DATA

Test Methods

Pancreas Procurement and Preservation

Islet Graft Preparation

INSTITUTION AND RECIPIENT IDENTIFICATION

If Cultured: DaysTemp (°C)

pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

NDCrossmatch

Pre Transplant Islet Viability Tests

Test Results

pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

ND pos.neg.

NDCMV

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

pre cult/cryopre tx

Volume Determination

02 (%)

Case # Date of TxLocal CodeInstitution # Transplant Center

HysterotomyCurettagePG E2Water Bag






Method of Abortion

Graft Volume

Storage Solution

Gestational Age (wks)1

ITR-R-93-1ITR-DF-93-1

International




Phone: (49)-641-702-7445, Fax:(49)-641-702-7443

FOLLOW -UP FORM FOR CLINICAL ISLET TRANSPLANTS

Primary NonfunctionRejectionInsuff. Islet Mass

Death of PatientUnknown

Full Partial FailedFull Partial Failed

Full Partial FailedFull Partial FailedFull Partial Failed

Date

Case # Date of TxLocal CodeInstitution # Transplant CenterINSTITUTION AND RECIPIENT IDENTIFICATION

Off InsulinResumed InsulinIslets Failed

Cause of Graft Failure

MaintenanceImmunosuppresssion

PreTx1 wk1 mo3 mo6 mo1 yr2 yrs3 yrs4 yrs5 yrs

CreaInsulin

U/day

HbA1c

%

GRAFT FUNCTION AND IMMUNOSUPPRESSION

Alive DeadPatient Status Date If not alive, give cause of death (related to islet tx?)

PATIENT STATUS

none until1st2nd

Organ Funct. after Rej. Epi.

REJECTION EPISODES

COMMENTS / COMPLICATIONS

none until1st2nd3rd

Anti-Rejection Therapy

Prednisone

mg/day

Islets:

Kidney:

ng/mLpmol/mL

mg/dLmmol/L

mg/dLµmol/L

Last Date of Completion

basal (fasting)C-Peptide Glucose

ng/mLpmol/mL

mg/dLmmol/L

SustacalStimulation

Index

stimulatedC-Peptide Glucose

NoneSteroidsCsAAZAFK 506

Please make sure that C-Peptide and Glucose Levels are corresponding, i.e. taken from the same sample or at least drawn at the same time !!

ITR-FU-93-1

Summary of Adult Islet Allografts (and one Xenograft*)according to Institution and Year

through Dec 31, 1992

• Bristol* 1893 1• Newcastle-upon-Tyne 1916 2• Padova 1927 2• New York 1935 1• Leiden 1944 1• Petah Tikva 1968 1• Minneapolis 1974-1992 33• Zurich 1977-1988 8• Genova 1978-1979 13• Hannover 1978 2• Detroit 1980-1985 7• Giessen 1980-1992 2• East-Berlin 1982-1987 8• St. Louis 1985-1992 24• Miami 1985-1992 12• Paris 1988-1991 7• Perugia 1989-1991 5• West-Berlin 1989 1• Edmonton 1989-1992 5• Milan 1989-1992 11• Pittsburgh 1990-1992 27• Leicester 1991-1992 3• Oxford 1991-1992 2• Charlestown 1991 2• Los Angeles 1992 3

INSTITUTION YEAR OF TX NO. OF CASES

TOTAL NO. OF CASES: 183TOTAL NO. OF INSTITUTIONS: 25

74-76 1980 1985 1990 1992

No. of Adult Islet Allografts by Year

No. of Adult Islet Allograftsby Year from 1974 through Dec 31, 1992

108

11 11

3 26

04

14

24

2

13

36

2623

0

5

10

15

20

25

30

35

40

74-76 1980 1985 1990 1992No. of Institutions by Year

No. of Institutions reporting Adult Islet Allografts by Year from 1974 through Dec 31, 1992

12

4

2 21 1

01

4

2 2 2

6

8

10 10

0123456789

10

Insulin Independence and Basal C-Peptide after Adult Islet Allotransplantation through Dec 31,1992 by

Era

total # of cases C-peptide 1ng/ml 1mo off insulin > 1 week

55

35 36

2623

3 36

2

27

12 10

1

15

5

1974-1984 1985-1989 1990 1991 19920

10

20

30

40

50

60

*

and according to Induction Immunosuppression

ALSALGATG

OKT 3

FK 506

Others


0 0

17

6 413

71 1

0

10

20

30

2315 18 17 17

2 4 2

145

91

135

1974-1984 1985-1989 1990 1991 19920

10

20

30

32

20

1 3 21 3 2 1

0

10

20

30

*

#

* for further information please see page 20 (upper table)# cluster transplants only, more data on page 20 (lower table)

Insulin Independence and Basal C-Peptideafter Adult Islet Allografts (and one Xenograft) through Dec 31, 1992 by

Site of Implantation

s.c i.m. intra- liver spleen kidney epiploic vasc. othersperitoneal capsule flap prosthesis


154 6

122

156 7 4 4

2

55

19

3 1 3 10

20

40

60

80

100

120

140

*

Insulin Independence and C-Peptide after Adult Islet Allografts (and one Xenograft) through Dec 31, 1992 according to

Recipient Category

ITA: Islet Transplantation Alone SIL: Simultaneous Islet-LiverIAK: Islet after Kidney SIKL: Simultaneous Islet-Kidney-LiverSIK: Simultaneous Islet-Kidney SIH-L: Simultaneous Islet-Heart-Lung


43

5660

21

2 12

20

6

26

6

149

1

ITA IAK SIK SIL SIKL SIH-L0

10

20

30

40

50

60

*

* for further information please see upper table on page 20

No. of Adult Islet Allograftsaccording to Institution and Year

• Charlestown - 2 - 2• Edmonton 2 - 1 3• Giessen - - 1 1• Leicester - 2 1 3• Los Angeles - - 3 3• Miami 4 2 1 7• Milan 4 3 3 10• Minneapolis 1 4 5 10• Oxford - 1 1 2• Paris 3 1 - 4• Perugia 1 1 - 2• Pittsburgh 17 6 4 27• St. Louis 4 4 3 11

36 26 23 85

1990 1991 1992

É

É

É

ÉÉ

ÉÉ

Ç

Ç

Ç

Ç Ç

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

% g

raft

su

rviv

al (

bas

al C

-pep

tid

e

1n

g/m

l)

month post tx

É 1990 (n = 24)

Ç 1991 (n = 16)

B 1992 (n = 13)

One-Year Islet Allograft Survival byYear of Transplant (1990 - 92)

The 1990-92 Period

In the 1990-92 period a total number of 85adult allotransplants were reported to theIslet Transplant Registry worldwide. Forthe analysis three patients had to be exclu-ded since provided data were far fro mbeing complete. Another six patients hadto be excluded due to clearly positive pre-transplant basal C-peptide levels (≥ 0.4 ng/ml). The pretransplant basal C-peptide levels of the remaining patientswere 0, < 0.1, < 0.2 and < 0.4 ng/ml in 19,34, 13 and 10 cases, re s p e c t i v e l y. Thus 76patients were taken into the analysis andthe results are depicted in bar charts onpages 13-19.In addition, adult islet allograft survival asassessed by basal C-peptide ≥ 1ng/ml overthe first year posttransplant in re g a rd toyear of transplantation, number of donorsetc. are illustrated on pages 12-19.Fifty-three patients have been included inthese survival charts , all of whom had com-plete 1-year follow-up data (for this re a-son, patients transplanted in the secondhalf of 1992 were not considered).

1 2 3 4

Insulin Independence and Basal C-Peptide according toNo. of Donors (1990 - 92)

No. of Donors

total # of cases C-peptide 1ng/ml 1mo off insulin > 1 week38

15

11 12

21

6

14

69

46

2

0

5

10

15

20

25

30

35

40

B

B

B

B

B

B

J

J

J

J

J

J

É

É

É

É

É

É

Ç

Ç

Ç Ç

Ç Ç

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

10

20

30

40

50

60

70

80

90

100

% g

raft

su

rviv

al (

bas

al C

-pep

tid

e

1n

g/m

l)

month post tx

B 1 donor (n = 24)

J 2 donors (n = 12)

É 3 donors (n = 9)

Ç 4 donors (n = 8)

One-Year Islet Allograft Survival according toNo. of Donors (1990 - 92)

Insulin Independence and Basal C-Peptide according toEquivalent Number of Islets (IEQ) (1990 - 92)

IEQ


36

26

14

20

5

21

10 9

3

< 500,000 500,000 - 1,000,000 > 1,000,0000

5

10

15

20

25

30

35

40

B

B

B

B

B

É

É

É É

É

É

É

Ç

Ç

Ç

Ç

Ç

Ç

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

10

20

30

40

50

60

70

80

90

100

% g

raft

su

rviv

al (

bas

al C

-pep

tid

e

1n

g/m

l)

month post tx

B < 500,000 (n = 24)

É < 1,000,000 (n = 18)

Ç > 1,000,000 (n = 11)

One-Year Islet Allograft Survival according toEquivalent Number of Islets (1990 - 92)

Insulin Independence and Basal C-Peptide according toCold Ischemia Time * (1990 - 92)


27

40

4 5

20

9

27

9

2 1

< 6 h 6 - 12 h > 12 h data incomplete0

5

10

15

20

25

30

35

40

* in case of multiple donors mean cold ischemia time was calculated

Insulin Independence and Basal C-Peptide according toPurity of Islet Tissue (1990 - 92)


68

8

45

16

52

purified tissue digested tissue0

10

20

30

40

50

60

70

Insulin Independence and Basal C-Peptide according toPreservation of Islet Tissue (1990 - 92)


55

11

5 5

39

14

74

2 2

fresh/culture fresh/culture & cryo cryo only not reported0

10

20

30

40

50

60

Insulin Independence and Basal C-Peptide according toSite of Tx (1990 - 92)


4

66

3 1 22

47

18

1

epiploic flap liver spleen kidney capsule vasc. prosthesis0

10

20

30

40

50

60

70

Insulin Independence and Basal C-Peptide according toInduction Immunosuppression (1990 - 92)


18

30

23

5

12

2

22

9

15

7

1

OKT3 ALS/ALG/ATG FK 506 others0

5

10

15

20

25

30

Insulin Independence and Basal C-Peptide according toRecipient Category (1990 - 92)


19

34

18

2 3

13

5

23

5

13

8

1

IAK SIK SIL ITA Others0

5

10

15

20

25

30

35

Insulin Independence and Basal C-Peptide according toHLA-ABDR-Mismatches * (1990 - 92)

No. of ABDR-Mismatches* In case of multiple donors, given HLA-ABDR-MM were added up,

divided by no. of donors and rounded up or down where necessary.


5

2425

22

31

19

7

14

3

14

7

0-2 3-4 5-6 incomplete HLA-data0

5

10

15

20

25

B

B

B B B

Ç

Ç

Ç

Ç

Ç

Ç

Ç

É

É

É

É

É

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

10

20

30

40

50

60

70

80

90

100

% g

raft

su

rviv

al (

bas

al C

-pep

tid

e

1n

g/m

l)

month post tx

B 0 - 2 MM (n = 4)

Ç 3 - 4 MM (n = 18)

É 5 - 6 MM (n = 18)

One-Year Islet Allograft Survival according toHLA-ABDR-MM (1990 - 92)

Insulin Independence and Basal C-Peptide according toHLA-DR-Mismatches * (1990 - 92)

No. of DR-Mismatches* In case of multiple donors, given HLA-DR-MM were added up, divided by no. of donors and rounded up or down where necessary.


5

22

29

20

3

17

8

18

4

12

6

0 1 2 incomplete HLA-data0

5

10

15

20

25

30

B

B

B B

É

É

É

É

É

É

É

Ç

Ç

Ç Ç

Ç

Ç

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

10

20

30

40

50

60

70

80

90

100

% g

raft

su

rviv

al (

bas

al C

-pep

tid

e

1n

g/m

l)

month post tx

B 0 MM (n = 4)

É 1 MM (n = 17)

Ç 2 MM (n = 20)

One-Year Islet Allograft Survival according toHLA-DR-MM (1990 - 92)

Institution Year No. of IEQ1 Site Period of Insulin Comments

of Tx Donors *1000 of Tx Independence post tx

Paris 1988 1 150,0002 epiploic flap 7th - 49th month post tx# hemochromatosis

Paris 1990 1 250,0002 epiploic flap 1st - 8th day simult. islet, liver and

kidney tx; CMV inf.Pittsburgh 1990 1 474,000 liver 2nd - > 42 month3 cluster tx/FK 506

Pittsburgh 1990 1 289,000 liver 2nd - 4th month cluster tx/FK 506 5

Pittsburgh 1990 2 578,000 liver 2nd - 15th month cluster tx/FK 506

Pittsburgh 1990 2 258,000 liver 5th - 15th month cluster tx/FK 506Pittsburgh 1990 1 285,000 liver 3rd - 10th month cluster tx/FK 506 5

Pittsburgh 1990 2 726,000 liver 2nd - 20th month cluster tx/FK 506 5

Pittsburgh 1990 2 332,000 liver 1st - 15th month cluster tx/FK 506 5

Milan 1992 2 830,000 liver 2nd - > 7th month4 residual C-peptide

secretion pre tx

1) IEQ = Islet equivalents 2) Number of Islets 3) as of June 10, 1993

4) as of June 11, 1993 5) died off insulin

Insulin Independence after Simultaneous Liver and Adult Islet Transplantation

Summary of Cases through 1992

Institution Year Rec. Site Period of Insulin Comments

of Tx Cat. of Tx Independence post tx

Zurich 1978 SIK spleen 10th - 20th month C-peptide not determ.

Minneapolis 1977 IAK liver 2nd - 4th day insulin leakage ?

Minneapolis 1978 IAK liver 13th - 17th day insulin leakage ?

Genova 1979 ITA s.c. 3rd - 10th month C-peptide data not available

Genova 1979 ITA s.c. 3rd - 19th month C-peptide data not available

Summary of Cases reported to be Off Insulinafter Adult Islet Tissue Transplantation

without detailed information

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❍

❍

❍

❍

❍

❍ ❍❍

❍

❍

❍❍

❍

❍

❍

❍

❍

pretransplant 1 year posttransplant4

5

6

7

8

9

10

11

12

Hb

A1c

(%

)

Basal C-Peptide 1ng/ml at 1 Year (n= 9)

❍ ❍

❍

❍

❍

❍

❍

❍

❍

❍

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5

6

7

8

9

10

11

12

Hb

A1c

(%

)

Basal C-Peptide < 1ng/ml at 1 Year (n=12)

Glycated Hemoglobin (HbA1c-levels) before and One Year after Adult Islet Allotransplantation according to Basal C-Peptide Levels

Insulin Independence after Adult Islet Transplantation in Type I Diabetes

Summary of cases through Dec 31, 1992

* IEQ: eqivalent no. of islets (number of islets if all were 150 micrometers in diameter)IAK: islet after kidney (islet transplantation in patients with established kidney grafts) 1 since then 4-8 U insulin per daySIK: simultaneous islet and kidney transplantation 2 as of June 11, 1993

† in the early posttransplant period 3 as of May 18, 1993

Year No. of Donors Site Type HLA match Induction Period of Insulin GlucoseInstitutionof Tx Fresh Cryo IEQ* 1000 of Tx of Tx AB DR Immunosuppression Independence post tx Control†

St. Louis 1989 1.4 - 785 p.v. IAK* 1/3 2/1 ALG (+M-Pred) 10th - 25th day IV InsulinSt. Louis 1990 1 + 2 550 + 555 p.v. IAK* 1/2/2 1/1/0 ALG (+M-Pred) 33rd - 341st day IV Insulin

Edmonton1990 1 + 4 243 + 368 p.v. SIK* 3 0 (fresh) ALG (+M-Pred, AZA, 69th - 821st day IV Insulin 1/0/2/0 0 (cryo) CsA at day 10)

Edmonton1992 1 + 5 284 + 308 p.v. SIK* 3 1 (fresh) ALG (+M-Pred, AZA, 155th - 166th day1 IV Insulin1/0/0/1/0 1/1/0/0/1 (cryo) CsA at day 8)

Milano 1990 1 - 592 p.v. IAK* 0 0 ALG (+M-Pred, CsA, AZA) 110th - 300th day1 IV InsulinMilano 1991 1 + 2 453 + 370 p.v. SIK* ND ND ALG (+M-Pred, CsA, AZA) 213th - > 539th day2 IV Insulin Milano 1992 2 - 613 p.v. IAK* ND ND ALG (+Pred, CsA, AZA) 48th - > 269th day2 IV Insulin

Miami 1990 3 - 1122 p.v. IAK* 0/2/0 1/1/0 OKT3 (+M-Pred, CsA, AZA) 42nd - 78th day IV InsulinMiami 1990 3 - 1209 p.v. IAK* 0/0/0 0/0/0 OKT3 (+M-Pred, CsA, AZA) 87th - 125th day IV Insulin

Mnpls 1992 1 - 536 p.v. SIK* 1 1 ALG (+Pred+CsA+DSG) 326th - > 453rd day3 IV Insulin

Mnpls 1992 1 - 626 p.v. SIK* 2 0 ALG (+Pred+CsA+DSG) 123rd - 231st day IV Insulin

Reported Fetal Islet Transplants according to No. of Donors (1979 - 91)

No. of Donors

54

1315

63

6

1

10 10 1014

6 73

63 2 1 0

6

1 2 3 4 5 6 7 8 9 12 11 12 13 14 15 16 17 18 19 200

10

20

30

40

50

60

Summary of Fetal Islet Grafts Reported to the Registry

according to Institution and Year through Dec 31, 1992

• Genova 79 - 80 13

• Shanghai 81 - 88 75

• Stockholm 82 - 84 3

• Szeged 82 - 92 25

• Melbourne 83 - 86 8

• Sydney 83 - 86 5

• Albany 85 1

• Dallas 85 6

• Denver 85 - 87 16

• Moscow 88 - 91 25

INSTITUTION YEAR OF TX CASES

TOTAL NO. OF CASES: 177TOTAL NO. OF INSTITUTIONS: 25

Fetal Islet GraftsAccording to the data reported in the literature or com-municated to the scientific community, fetal islet tissuehas been transplanted to approximately 2,000 diabeticrecipients (see Newsletter No. 1). In this Newsletter, re s u l t son the 177 grafts only, which have been reported to theRegistry are presented. These reports are very muchappreciated since they facilitate to start with the evalua-tion of the potential impact of fetal islet tissue trans-plantation. The first two figures are a breakdown of 177 fetal isletgrafts according to the number of fetal donor pancreataand according to the recipient category, re s p e c t i v e l y. Thelast two pairs of figures compare the highest basal C-peptide levels and the lowest insulin re q u i rements within the first year following fetal and adult islet tissuetransplantation.Similar to the exclusion criteria of the 1990-92 period,only cases holding pre- as well as posttransplant dataw e re considered, resulting in only 66 fetal cases with pre -and posttransplant C-peptide data. It is interesting thata reduction of insulin re q u i rement appeared in both adultand fetal islet transplant recipients, although posttrans-plant basal C-peptide levels ≥ 1 ng/ml were frequentlyreported in the adult islet transplant group but not in asingle case in the fetal islet transplant group. In the thre efetal islet transplants, which were reported to be insulinindependent, no pretransplant C-peptide levels weregiven and the basal C-peptide levels within one year werein the range of 0.6 and 0.9 ng/ml.

140

18 154

ITA IAK SIK not reported0

20

40

60

80

100

120

140

Reported Fetal Islet Transplants according to Recipient Category (1979 - 91)

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Dai

ly in

sulin

req

uir

emen

t (U

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ly in

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Bas

al C

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e (n

g/m

l)

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1

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Bas

al C

-pep

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l)

Islet Transplant Success in Terms of Lowest Daily Insulin Requirementand Highest Basal C-Peptide within one Year Posttransplant

Fetal Cases (n=147)Fetal Cases (n=147) Fetal Cases (n=147)Adult Cases (n=51)

Adult Cases (n=51)Fetal Cases (n=147)Fetal Cases (n=66)

Abri O 1st Dept. of SurgeryKrankenhaus MoabitD-1000 Berlin 21, GERMANYPhone: (49)-30-3937-1

Alejandro R & Mintz DHDiabetes Research Institute (R-134)Univ. of Miami School of MedicineMiami, FL 33101, USAPhone: (1)-305-547-6657Fax: (1)-305-548-4404

Altman JJ Diabétol.-Nutrition-TransplantationHôpital LaennecF-75340 Paris, FRANCEPhone: (33)-1-4439-6651Fax: (33)-1-4439-6633

Atkinson P (in coop. with St. Louis)Multiorgan Transplant ServiceUniversity HospitalLondon, Ontario N6A 5A5, CANADAPhone: (1)-519-663-3179Fax: (1)-519-663-3858

Calafiore R & Brunetti PIstituto di Patologia Speciale MedicaUniversity of PerugiaI-06100 Perugia, ITALYPhone: (39)-75-21366Fax: (39)-75-469-2067

Cerilli GJDept. of SurgeryAlbany Medical CollegeAlbany, NY 12208, USA

Coulic V Faculty of MedicineUniv. of People’s Friendship P. LumumbaMoscow 117198, RUSSIA

Dawidson I & Raskin PDept. of SurgeryUniversity of Texas at DallasDallas, TX 75235, USA

Farkas G Dept. of SurgeryA. Szent-Györgyi Medical UniversityH-6701 Szeged, HUNGARYPhone: (36)-62-22-444

Faustman DL Massachusetts General Hospital EASTHarvard Medical SchoolCharlestown, MA 02129, USAPhone: (1)-617-726-4080Fax: (1)-617-726-4095

Gores PF & Sutherland DER Dept. of SurgeryUniversity of MinnesotaMinneapolis, MN 55455, USAPhone: (1)-612-626-2101Fax: (1)-612-625-4453

Gray DWR & Morris P Nuffield Dept. of SurgeryUniversity of OxfordHeadington, Oxford OX3 OEX, UKPhone: (44)-865-22-6092Fax: (44)-865-22-5773

Groth CG Dept. of Transplantation SurgeryKarolinska Institute StockholmS-141 86 Huddinge, SWEDENPhone: (46)-8-746-1000Fax: (46)-8-746-7733

Hering BJ, Bretzel RG & Federlin K 3 rd Dept. of MedicineUniversity of GiessenD-35392 Giessen, GERMANYPhone: (49)-641-702-7445Fax: (49)-641-702-7443

Hu Y-FDiabetes Research LaboratoryShanghai First People’s HospitalShanghai 200085, PR of CHINA

Kühn F, Lorenz D, Lippert H & Wolff HDept. of SurgeryHumboldt University (Charité)D-1040 Berlin, GERMANYPhone: (49)-30-2802-3881Fax: (49)-30-2802-1323

Largiadèr FDept. of Surgery AUniversity of ZurichCH-8091 Zurich, SWITZERLANDPhone: (41)-1-255-1111Fax: (41)-1-255-4442

London NJM, James RFL & Bell PRF Dept. of SurgeryUniv. of Leicester School of MedicineLeicester LE2 7LX, UKPhone: (44)-533-523-142Fax: (44)-533-523-179

Mandel TEWalter & Eliza Hall Inst. of Med. Res.University of MelbourneParkville, Victoria 3050, AUSTRALIAPhone: (61)-3-345-2555Fax: (61)-3-347-0652

Mullen Y, Watt PC & Brunicardi FCDiabetes Research CenterUniv. of California at Los AngelesLos Angeles, CA 90024-7036, USAPhone: (1)-310-825-4359Fax: (1)-310-794-7173

Pichlmayr R & Rumpf KDDept. of Abd. and Transplant SurgeryMedical School of HannoverD-3000 Hannover 61, GERMANYPhone: (49)-511-532-3440Fax: (49)-511-556747

Ricordi C, Carroll P, Tzakis A & Starzl TDept. of SurgeryUniversity of PittsburghPittsburgh, PA 15261, USAPhone: (1)-412-624-4616Fax: (1)-412-624-6666

Scharp DW, Flavin K & Lacy PE Islet Transplant CenterWashington Univ. School of MedicineSt. Louis, MO 63110, USAPhone: (1)-314-362-8320Fax: (1)-314-361-0426

Socci C, Maffi P, Di Carlo V & Pozza GDiv. di Medicina I et Chirurgica II Ospedale San RaffaeleI-20129 Milano, ITALYPhone: (39)-2-2643-2323Fax: (39)-2-2643-2482

Spees E & Lafferty KJ A.M.I. St. Luke’s HospitalUniversity of ColoradoDenver, CO 80262, USA

Toledo-Pereyra LDept. of SurgeryMt. Carmel Mercy HospitalDetroit, MI 48235, USA

Tuch BDept. of Endocrinology & MetabolismThe Prince of Wales HospitalSydney, N.S.W. 2031, AUSTRALIAPhone: (61)-2-399-1828Fax: (61)-2-398-9887

Urca I Dept. of SurgeryBeilinson HospitalPetah Tikva, ISRAEL

Valente UTransplant UnitUniversita di GenovaI-16132 Genova, ITALY

Warnock GL, Lakey JRT & Rajotte RVSurgical-Medical Research InstituteUniversity of AlbertaEdmonton T6G 2N8, CANADAPhone: (1)-403-492-4595Fax: (1)-403-492-1627

Acknowledgementshis Newsletter reflects the collaborative efforts of the followingenters engaged in clinical transplantation of adult and fetalslets. Their support to the Registry is gratefully acknowledged.

The asterix indicates the centers that have sent report forms tohe International Pancreas and Islet Transplant Registry in

Minneapolis in former years. When the responsibility for theslet component was transferred to Giessen, these forms wereraciously passed on to the Islet Transplant Registry by Dr. David

E.R. Sutherland and Kay C. Moudry-Munns.

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