CITR Annual Report Exhibits

CITR Annual Report ExhibitsCollaborative Islet Transplant Registry (CITR)

2009 Annual ReportExhibits

Prepared by:

CITR Coordinating CenterThe EMMES Corporation

Rockville, MD

Sponsored by:National Institute of Diabetes & Digestive & Kidney Diseases

National Institutes of HealthJuvenile Diabetes Research Foundation

Datafile Closure: April 1, 2009

Collaborative Islet Transplant Registry 2009.Follow-up time after initial infusion for each recipient. Top: islet after kidney (N=65), bottom: islet alone (N=347).

Yellow: insulin independence; green: insulin-using with graft function (70% average reduction in daily insulin use from baseline); black: no islet function; gray: missing data. Red marks indicate reinfusions.

Pie charts show percent of all follow-up time with insulin independence.

Insulin Dependent46.5

Insulin Independent17.6

No Data15.0

No Graft Function20.8

Insulin Dependent37.9

Insulin Independent25.9

No Data14.5

No Graft Function21.6

Table of Contents

Chapter 1: Islet Transplant Activity

Chapter 2: Recipient and Donor Characteristics

Chapter 3: Pancreas Procurement, Islet Processing, and Infusion

Characteristics

Chapter 4: Immunosuppression and Other Medications

Chapter 5: Graft Function

Chapter 6: Liver, Kidney, Lipid, and PRA Effects

Chapter 7: Adverse Events

Chapter 8: Registry Data Quality Review

CITR Coordinating Center

CITR Committees

Chapter 1: Islet Transplant Activity

Islet Transplant Centers Reporting Data to CITR:Participating North American Centers 1999-2008

A - CITR Centers with at least one islet allograft infusion procedure conducted in 2008C - CITR Centers with no islet allograft infusions in 2008D - CITR Coordinating Center

Islet Transplant Centers Reporting Data to CITRParticipating European Centers 1999-2008

A - CITR Centers with at least one islet allograft infusion procedure conducted in 2008B - CITR Centers with data reports pending

Islet Transplant Centers Reporting Data to CITRParticipating Australian Centers 1999-2008

A - CITR Centers with at least one islet allograft infusion procedure conducted in 2008C - CITR Centers with no islet allograft infusions in 2008

Number of Islet Transplantation Centers Performing Islet Allografts per Year and Number with Data Entered in CITR Database

All North American Islet Transplant Centers 1999-2008

All North American Centers Performing Islet Allografts (N=32)CITR-Participating Centers with Data Entered (N=27)

6

2

9

6

16

11

14

11

20

16

23

20

1615

109

1514

Num

ber o

f Cen

ters

0

5

10

15

20

25

1999-2000 2001 2002 2003 2004 2005 2006 2007 2008

Total Number of Islet Allograft Recipients, Recipients at CITR-Participating Centers, and Recipients with Detailed Data Reported to CITR by Year of First Islet Allograft Infusion

All North American Islet Transplant Centers 1999-2008

The Islet Transplant Summary (ITS) questionnaire is completed by all North American Islet Transplant Programs regardless of their participation in the Registry. Of 46 North American islet transplant programs polled, all have provided this information through 2007.

All North American Recipients (N=408)All North American CITR Recipients (N=368)Recipients with Detailed Data Reported to CITR (N=329)

30 30

15

45 44

36

8275

71

4538 37

53

4541

6558 55

3631 30

20 19 19

3228

25

Num

ber o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

1999-2000 2001 2002 2003 2004 2005 2006 2007 2008

Total Number of Islet Allograft Recipients and Recipients with Detailed Data Reported to CITR by Year of First Islet Allograft Infusion

CITR-Participating European and Australian JDRF Centers 1999-2008

All European and Australian CITR Recipients (N=183)Recipients with Detailed Data Reported to CITR (N=83)

36

47

1

25

7

16

12

22

10

23

13

21

1316

12

17

11

Num

ber o

f Pro

cedu

res

0

5

10

15

20

25

30

35

40

1999-2000 2001 2002 2003 2004 2005 2006 2007 2008

Total Number of Islet Allograft Infusion Procedures Performed andNumber with Data Reported to CITR

CITR-Participating North American Islet Transplant Centers 1999-2008

All Infusions for North American Recipients (N=783)All Infusions for North American CITR Recipients (N=694)Infusions with Data Reported to CITR (N=637)

50 50

31

64 63

49

142132

125

106

91 88

110

9587

125113109

7865 65

4234 34

66

51 49

Num

ber o

f Pro

cedu

res

0

20

40

60

80

100

120

140

160

1999-2000 2001 2002 2003 2004 2005 2006 2007 2008

Total Number of Islet Allograft Infusion Procedures Performed and Number with Data Reported to CITR

CITR-Participating European and Australian JDRF Centers 1999-2008

All Infusions for European and Australian CITR Recipients (N=326)Infusions with Data Reported to CITR (N=182)

50

912

4

38

12

34

27

42

24

52

32

43

29 28

22

2723

Num

ber o

f Pro

cedu

res

0

10

20

30

40

50

60

1999-2000 2001 2002 2003 2004 2005 2006 2007 2008

Total Number (N=828) of Islet Allograft Infusion Procedures Conducted andEntered in CITR Database, by Year and Infusion Procedure NumberCITR-Participating North American and JDRF Centers, 1999-2008

First infusionSecond InfusionThird InfusionFourth Infusion

4053

137

115 111

141

94

56

72

9Num

ber o

f Isl

et In

fusi

ons

015

30

45

6075

90

105120

135

150

1999-2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Number (N=828) of Islet Allograft Infusion Procedures Per Recipient:CITR-Participating North American and JDRF Centers, 1999-2008

Islet Alone RecipientsIslet After Kidney Recipients

107

202

95

8

Num

ber o

f Rec

ipie

nts

020406080

100120140160180200220

Total Number of Infusions Received1 2 3 4

Total Number (N=905) of Deceased Donors per Islet Allograft Infusion ProcedureCITR-Participating North American and JDRF Centers, 1999-2008

754

71

3

Num

ber o

f Isl

et A

llogr

aft I

nfus

ions

050

100150200250300350400450500550600650700750800

Total Number of Donors Received1 2 3

Islet Alone and Islet After Kidney RecipientsCITR-Participating North American and JDRF Centers, 1999-2008

Islet Alone347

Islet After Kidney65

Chapter 2: Recipient and Donor Characteristics

Recipient Demographics

Transplant Recipient Primary Funding InformationCITR-Participating US Centers

Recipient Characteristics at First Infusion

Recipient Diabetes Characteristics at First Infusion

Recipient Autoantibodies at First Infusion

Recipient Infectious Disease Testing at First Infusion

Recipient Characteristics at First Infusion by Total Number of Infusions Received

Recipient Demographics and Characteristics at First Infusionby Total Number of Infusions Received

Recipient Laboratory Values at First Infusion

Donor DemographicsAll Allograft Donors

Donor CharacteristicsAll Allograft Donors

Donor CharacteristicsAll Allograft Donors (continued)

Characteristics of Organ Procurement and Donor Cause of DeathAll Allograft Donors

Treatments Given to Donor During HospitalizationAll Allograft Donors

Treatments Given to Donor During HospitalizationAll Allograft Donors (continued)

Donor SerologyAll Allograft Donors

Donor Laboratory DataAll Allograft Donors

Organ Crossmatch ResultsAll Allograft Donors

Chapter 3: Pancreas Procurement, Islet processing and Infusion Characteristics

Pancreas Procurement and Islet Processing

Pancreas Procurement and Islet Processing (continued)

Cold Ischemia Information

Islet Equivalents and Timing of Count

Islet Product Characterization

Islet Product and Infusion Characteristics by Infusion Sequence

Univariate Analysis of Islet Characteristicsby Pancreas Preservation Method

Significant Relationships (p<0.05) between Islet Outcomes and Categorical PredictorsUnivariate Analysis

Significant Relationships (p<0.05) between Islet Outcomes and Categorical PredictorsUnivariate Analysis (continued)



Univariate Correlation of Islet Characteristics with Donor, Recovery, and Processing Characteristics

Univariate Correlation of Islet Characteristics with Donor, Recovery, and Processing Characteristics (continued)



Pre Infusion Portal Pressure by Infusion Sequence

348 248 77

1 2 3

0

5

10

15

20

25

30

mm

Hg

Infusion Sequence

Peak Portal Pressure by Infusion Sequence

328 239 75

(One at infusion 1)Values greater than 40 mmHg are not displayed

1 2 3

0

10

20

30

40

mm

Hg

Infusion Sequence

Closure Portal Pressure by Infusion Sequence

343 246 76

1 2 3

0

10

20

30

40

mm

Hg

Infusion Sequence

Change from Pre Infusion to Closure Portal Pressure by Infusion Sequence

340 245 75


1 2 3

-10

-5

0

5

10

15

20

mm

Hg

Infusion Sequence

Change from Pre Infusion to Peak Portal Pressure by Infusion Sequence

327 237 72


1 2 3

-10

-5

0

5

10

15

20

mm

Hg

Infusion Sequence

Cell Volume Infused per Infusion by Infusion Year

15 24 49 121 95 91 120 83 46 50

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

Cel

l Vol

ume

(mL)

Infusion Year

This graph represents either settled or packed cell volumes depending on center procedure. Higher volumes typically represent

unpacked cells.

IEQs Infused per Infusion by Infusion Year

15 24 50 123 106 104 134 93 55 65

(One at 2005)Values greater than 1250000 are not displayed

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

0

250000

500000

750000

1000000

1250000

IEQ

s

Infusion Year

Chapter 4: Immunosuppression and other Medications

Immunosuppression Regimen at Time of First Infusion

Immunosuppression Regimen at Time of First Infusion (continued)

Biologic Agents Used Peri First Infusion for Induction Therapy

Biologic Agents Used Peri First Infusion for Induction Therapy

Ant i CD3*Ant i I L2Al oneAnt i I L2+DSGAnt i I L2+TNFBMonoTCDAl one

MonoTCD+Ant i I L2/ TNFBPol yTCD al onePol yTCD+TNFBPol yTCD+AI L2( +/ - TNFB)Unr epor t ed

99- 00

01- 02

03- 04

05- 06

07- 08Year of 1st I nf usi on

1 2 3I nf usi on Sequence

19 13 4

115 62 9

100 86 36

111 88 30

67 41 16

Induction immunosuppression combinations given to allograft recipients, according to infusion sequence (horizontal axis), and transplantation

era (1999-2000, 01-02. etc, perspective axis). Substantial shifts away from Anti-IL2 alone (blue) to other combinations is evident in recent time

periods.

Immunosuppression Therapy Use at Specified Times Post Last Infusion Allograft Recipients without Reported Graft Failure at the Time of Follow-Up

Immunosuppression Therapy Use at Specified Times Post Last Infusion Allograft Recipients without Reported Graft Failure at the Time of Follow-Up

(continued)

Maintenance Immunosuppression Therapy Use Post Initial Infusionby Transplantation Era

Cal ci neur i nI nh+mTORCal ci neur i nI nh+I nosi neI nhCal ci ner i nI nh+mTOR+I nosi neI nhmTOR Al one/ +I nosi neI nh/ +St er oi d

Al l Ot her Combi nat i onsGr af t Fai l ur eNo Dat a

99- 00

01- 02

03- 04

05- 06

07- 08Year of 1st I nf usi on

0 6 12 24 36 48 60Mont hs Post Fi r st I nf usi on

19 19 19 19 19 19 19

115 115 115 115 115 115 113

100 100 100 100 100 91 46

111 111 111 111 75 6

67 50 39 5

Maintenance immunosuppression combinations given to allograft recipients, according to time (months from initial infusion, horizontal axis), and

transplantation era (1999-2000, 01-02. etc, perspective axis). The total number expected at each follow-up time point is accounted for. Complete graft

loss trumps any immunosuppression. Substantial shifts away from the Calcineurin+mTOR combination (yellow) to other combinations is evident from

the start in recent time periods )2007-2008), as well as among those infused in earlier eras (e.g., 2001-2006) and still on immunosuppression at long-term

follow-up (2-5 years).

Sirolimus Recipient Trough Level (ng/mL) Post Last InfusionAll Allograft Recipients

218 66 225 178 113 71 37

(One at inf 1 day 30 and one at inf 3 day 30)Values greater than 60 ng/mL are not displayed

Inf 1Day 30

Inf 2Day 30

Inf 3Day 30

Month 6Year 1 Year 2 Year 3 Year 4

0.00

10.00

20.00

30.00

40.00

50.00S

irolim

us T

roug

h (n

g/m

L)

Follow-Up

292

Tacrolimus Recipient Trough Level (ng/mL) Post Last InfusionAll Allograft Recipients

222 69 238 206 142 87 57

Inf 1Day 30

Inf 2Day 30

Inf 3Day 30

Month 6Year 1 Year 2 Year 3 Year 4

0.00

5.00

10.00

15.00

20.00

Tacr

olim

us T

roug

h (n

g/m

L)

Follow-Up

301

Anti-Hypertensive Medications Pre Infusion and Post Last InfusionAll Allograft Recipients

Total Number of Anti-Hypertensive Medications Pre Infusion and Post Last Infusion

All Allograft Recipients

Total Number of Medications 4321

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

Pre Infusion 1 Month 6 Year 1 Year 2 Year 3 Year 4

Lipid Lowering Medications Pre Infusion and Post Last InfusionAll Allograft Recipients

Total Number of Lipid Lowering MedicationsPre Infusion and Post Last Infusion


Total Number of Medications 21

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

Pre Infusion 1 Month 6 Year 1 Year 2 Year 3 Visit Year 4

Adjunctive Therapy Used at Time of First InfusionAll Allograft Recipients

VitaminsRosiglitizonePioglitazonePentoxifyllinePantoprazole

Ondansetron HydrochlorideNicotinamide

MetforminIron Supplements

EnoxaparinAspirin

AntiviralsAntifungalsAntibiotics

Percent of Recipients0 10 20 30 40 50 60 70 80 90 100

Adjunctive Therapy Post Last InfusionAll Allograft Recipients

Chapter 5: Graft Function

Insulin Independence, Insulin Dependence, Absence of Fasting C-peptide, or Re-Infusion

Post First InfusionA. Islet Alone Recipients

*Year 3 status regardless of re-infusion

Recipient Status Re-Infused Prior to Follow-UpInsulin IndependentInsulin Dependent with Detectable Fasting C-peptideNo Detectable Fasting C-peptide or Known Graft LossMissing Data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

Day 30N=347

Day 75N=346

Month 6N=328

Year 1N=318

Year 3*N=257

Insulin Independence, Insulin Dependence, Absence of Fasting C-peptide, or Re-Infusion

Post First Infusion B. Islet After Kidney Recipients

*Year 3 status regardless of re-infusion

Recipient Status Re-Infused Prior to Follow-UpInsulin IndependentInsulin Dependent with Detectable Fasting C-peptideNo Detectable Fasting C-peptide or Known Graft LossMissing Data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

Day 30N=65

Day 75N=65

Month 6N=65

Year 1N=61

Year 3*N=47

Insulin Independence, Insulin Dependence or Absence of Fasting C-peptide

Post Last Infusion A. Islet Alone Recipients

Recipient Status Insulin IndependentInsulin Dependent with Detectable Fasting C-peptideNo Detectable Fasting C-peptide or Known Graft LossMissing Data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Month 6N=314

Year 1N=298

Year 2N=266

Year 3N=216

Year 4N=155

Insulin Independence, Insulin Dependence or Absence of Fasting C-peptide

Post Last InfusionB. Islet After Kidney Recipients


Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Month 6N=63

Year 1N=59

Year 2N=49

Year 3N=42

Year 4N=35

Insulin Independence, Insulin Dependence, or Absence of Fasting C-peptidePost Last Infusion by Total Number of Infusions Received

Islet Alone RecipientsA. Recipients of 1 Infusion


Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Month 6N=81

Year 1N=77

Year 2N=63

Year 3N=48

Year 4N=37


Islet Alone RecipientsB. Recipients of 2 Infusions


Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Month 6N=155

Year 1N=147

Year 2N=133

Year 3N=112

Year 4N=77


Islet Alone RecipientsC. Recipients of 3 Infusions


Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Month 6N=78

Year 1N=74

Year 2N=70

Year 3N=56

Year 4N=41

Prevalence of Insulin Independence Post Last InfusionIslet Alone Recipients

Best Case Reported Worst Case

Per

cent

Insu

lin In

depe

nden

t

0

10

20

30

40

50

60

70

Months Post Last Infusion0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48

Prevalence of Insulin Independence Post Last Infusion By Total Number of Infusions Received

Islet Alone Recipients

Total Number of Infusions Received OneTwo

Three+

Per

cent

Insu

lin In

depe

nden

t

0

10

20

30

40

50

60

70

Months Post Last Infusion0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48

Achievement of Insulin Independence

Persistence of Insulin IndependenceAllograft Recipients Achieving Insulin Independence

Average Daily Insulin (Units) Baseline and Post Last Infusion

A. Islet Alone Recipients

330 279 258 221 171 114


0

20

40

60

80

100A

vera

ge D

aily

Insu

lin U

se (U

nits

)

Follow-Up

Average Daily Insulin (Units) Taken By Recipients on Insulin

Baseline and Post Last InfusionB. Islet After Kidney Recipients

62 51 48 38 32 23


0

20

40

60

80

100

Ave

rage

Dai

ly In

sulin

Use

(Uni

ts)

Follow-Up

Average Daily Insulin (Units/Kg)Baseline and Post Last Infusion


326 279 258 221 170 114


0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

Ave

rage

Dai

ly In

sulin

Use

(Uni

ts/k

g)

Follow-Up

Average Daily Insulin (Units/Kg)Baseline and Post Last InfusionB. Islet After Kidney Recipients

60 51 48 38 32 23


0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

Ave

rage

Dai

ly In

sulin

Use

(Uni

ts/k

g)

Follow-Up

Percent of Baseline InsulinFollow-Up Post Last Infusion


0%<25%25-49%50-74%>=75%Missing Data

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Month 6N=314

Year 1N=298

Year 2N=266

Year 3N=216

Year 4N=155

Percent of Baseline InsulinFollow-Up Post Last Infusion

B. Islet After Kidney Recipients

0%<25%25-49%50-74%>=75%Missing Data

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Month 6N=63

Year 1N=59

Year 2N=49

Year 3N=42

Year 4N=35

Complete Islet Graft Failure Post Last InfusionA. Islet Alone Recipients

Complete Graft FailureMissing DataGraft Function

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Day 30N=347

Month 6N=314

Year 1N=298

Year 2N=266

Year 3N=216

Year 4N=155

Complete Islet Graft Failure Post Last InfusionB. Islet After Kidney Recipients

Complete Graft FailureMissing DataGraft Function

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Day 30N=65

Month 6N=63

Year 1N=59

Year 2N=49

Year 3N=42

Year 4N=35

Persistence of Graft FunctionAll Allograft Recipients

Outcomes Post First Infusion

Outcomes Post Second Infusion

Outcomes Post Third Infusion

Primary Outcomes Post First Infusion Up to Re-Infusion, Complete Islet Failure, or Last Follow-Up According to Pre-Infusion Recipient,

Donor, Procurement, and Islet CharacteristicsIslet Alone Recipients


Donor, Procurement, and Islet CharacteristicsIslet Alone Recipients (continued)











Achievement of Insulin Independence Post First Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval)

Of Factors Univariately Significant p < 0.10Factors

Etanercept

Anti-CD3

Cumulative IEQs infused/kg recipient (100s) Cumulative IEQs infused (1000s)

Total volume infused over all infusions (ml)Total IEQs at time of islet count (1000s)

Viability > 87% (0=N 1=Y) Islet Viability (%)

Cold ischemia time (hrs)

Death to pancreas recovery (hrs)

Donor(s) CMV+ / Recipient CMV- (0=N 1=Y) Donor(s)-recipient BMI difference (x10)

Donor(s)-recipient age difference (x10-yrs)

Gradient type

Procurement/infusion teams (0-Unrelated 1-Related)

Donor(s) BMI Donor(s) BSA

Donor(s) weight (10-kg) Donor(s) given steroids (0=N 1=Y)

Donor(s) given vasopressors (0=N 1=Y)

Donor(s) blood type (1=A,B,AB 2=O) Donor race (0=W 1=Non-white)

Baseline fasting glucose (mg/dL) Baseline HbA1c (%)

Baseline number of daily insulin injectionsBaseline BMI

Baseline weight (10-kg) Baseline daily insulin use (Units)

Recipient gender (0=M 1=F) -1

Hazard ratio (95% CI)

0.125 0.25 0.5 1 2 4 8

Loss of Insulin Independence Post First Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval)


Monoclonal anti-IL2R + calc inh + (mtor OR inosine) Poly or mono T-cell AB + calc inh + (mtor OR inosine)

Sirolimus

Daclizumab

Anti-Il2

Total volume infused over all infusions (ml)

Total endotoxin infused/kg donor Total endotoxin infused

Total insulin content of islets Total beta cells/kg donor

Stimulation index <2/2-3.5/>=3.5 Stimulation index

Cold ischemia time (hrs)

Genders match (0=N 1=Y)

Culture time (hrs) Cultured >6 hrs (0=N 1=Y)

Processing/infusion center (0-Unrelated 1-Related) Procurement/infusion teams (0-Unrelated 1-Related)

Donor(s) ALT Donor(s) AST

Donor(s) insulin (0=N 1=Y)

Donor(s) given vasopressors (0=N 1=Y) Donor(s) ETOH (0=N 1=Y)

Donor(s) Hispanic (0=N 1=Y)

Baseline C-peptide (ng/mL) Baseline HbA1c (%)

Diabetes Duration (years)

Cohort 1999-2004/05-08 -1


0.125 0.25 0.5 1 2 4 8

Complete Islet Failure Post First Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval)


MonoAntiIL2R+TNFa+CalcInh+mTOR/inosine

Tacrolimus Calcineurin inhibitor

Etanercept TNF blocker

Isletsize (0-small 1-large) IEQ/islet particle ratio

Total beta cells/kg donor

Donor(s)-recipient age difference (x10-yrs) Culture time (hrs)

Cultured >6 hrs (0=N 1=Y)

Processing/infusion ctr (0-Unrelated 1-Related)


Donor race (0=W 1=Non-white)

Baseline total positive AABs (0,1,2,3) Baseline insulin AABs (0,1)

Baseline IA-2 AABs (0,1) Baseline GAD 65 AABs (0,1)

Baseline HbA1c (%) Intensive therapy <10/10-25/>=25 yrs

Years intensive therapy

Baseline BMI

Diabetes Duration (years) Recipient age (years)

-1


0.125 0.25 0.5 1 2 4 8

Reinfusion Post First Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval)


Monoclonal anti-IL2R + calc inh + (mtor OR inosine) Poly/mono T-cell AB + TNF-a + CalcInh + mTOR/Inosine

Poly/mono T-cell AB + CalcInh + mTOR/nosine) Prednisone, Methylprednisolone, or other steroid

MMF Inosine: MMF or mycophenolic acid

Sirolimus Sirolimus or Everolimus


Etanercept Infliximab

TNF blocker Anti-CD3

Daclizumab Anti-Il2

Rabbit thymoglobulin Poly T-cell depleting

IEQ/islet particle ratio Cumulative IEQs infused/kg recipient (100s)

Cumulative IEQs infused (1000s) Total volume infused over all infusions (ml)

Total IEQs at time of islet count (1000s) Endotoxin/kg <0.6/.06-3.0/>=3.0

Total beta cells/kg donorTotal beta cells (1000s)

Viability > 87% (0=N 1=Y) Islet Viability (%)

Death to transplant (hrs) Death to cross-clamp (hrs) Recovery to transplant (hrs)

Death to pancreas recovery (hrs)

Recipient insulin day 0 (0=N 1=Y)

Donor(s)-recipient BMI difference (x10) Donor(s)-recipient age difference (x10-yrs)

Collagenase (1=Liberase alone 2=Other)

Any positive crossmatch (0=N 1=Y)

Donor(s) serum lipase

Donor(s) BMI Donor(s) BSA

Donor(s) weight (10-kg) Donor(s) insulin (0=N 1=Y)

Donor(s) ETOH (0=N 1=Y)

Donor(s) blood type (1=A,B,AB 2=O)

Donor age (x10 yrs)

Baseline HbA1c (%)

Baseline use of insulin pump (0=N 1=Y)

Baseline weight (10-kg) Baseline daily insulin use (Units)

Recipient gender (0=M 1=F) Cohort 1999-2004/05-08

-1


0.125 0.25 0.5 1 2 4 8

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor, Procurement, and Islet Characteristics


(continued)


(continued)


(continued)


(continued)


(continued)

Achievement of Insulin Independence Post Last Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval)

of Factors Univariately Significant p < 0.10Factors

Reexposed to B locus mismatch Number of A/B/DR/DQ locus mismatches

Number of A/B/DR locus mismatches Number of Class I locus mismatches

Number of B locus mismatches Number of A locus mismatches

MonoAntiIL2R + CalcInh + mTOR/Inosine Poly/MonoT-cellAB + TNF-aAnt + CalcInh + mTOR/Inosine

MMF Inosine: MMF or mycophenolic acid


Daclizumab

Anti-Il2

Rabbit thymoglobulin Poly T-cell depleting

Viability > 87% (0=N 1=Y)

Recovery to transplant (hrs) Time from admission to death (hrs)

Recipient insulin day 0 (0=N 1=Y)

Gradient type


Donor(s) BUN Donor(s) creatinine

Donor(s) height (cm)

Donor(s) given steroids (0=N 1=Y)

Donor(s) ETOH (0=N 1=Y)

Donor race (0=W 1=Non-white) Donor(s) Hispanic (0=N 1=Y)

Baseline HbA1c (%)


0.125 0.25 0.5 1 2 4 8

Loss of Insulin Independence Post Last Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval)


MonoAnti-IL2R + CalcInh + mTOR/Inosine

Prednisone, Methylprednisolone, or other steroid MMF

Inosine: MMF or mycophenolic acid Sirolimus

Infliximab

Daclizumab

Anti-Il2

Rabbit thymoglobulin Isletsize (0-small 1-large)

Donor(s)-recipient age difference (x10-yrs)

Processing/infusion center (0-Unrelated 1-Related)

Donor(s) bilirubin


Donor(s) given vasopressors (0=N 1=Y)

Donor age (x10 yrs)

Baseline GAD 65 autoantibodies (0,1) Baseline C-peptide (ng/mL)

Baseline use of insulin pump or >=3 insulin inject

Baseline daily insulin use (Units) Diabetes Duration (years)


0.125 0.25 0.5 1 2 4 8

Complete Islet Failure Post Last Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval)


Reexposed to A locus mismatch

MonoAnti-IL2R + TNF-aAnta + CalcInh + mTOR/Inosine

MMF


Etanercept TNF blocker Daclizumab

Anti-Il2

Horse thymoglobulin

Total beta cells/kg donor Viability > 87% (0=N 1=Y)

Islet Viability (%) Stimulation index

Death to transplant (hrs) Recovery to transplant (hrs)

Donor(s)-recipient age difference (x10-yrs) Culture time (hrs)

Cultured >6 hrs (0=N 1=Y)


Donor(s) BMI

Donor race (0=W 1=Non-white)

Total donors Baseline total positive autoantobodies (0,1,2,3)

Baseline IA-2 autoantibodies (0,1) Baseline C-peptide (ng/mL)

Baseline HbA1c (%) Intensive therapy <10/10-25/>=25 yrs

Years prior to first inf using ins pump or >= 3 in

Baseline use of insulin pump (0=N 1=Y)

Diabetes Duration (years) Employment impacted by dx

Recipient age (years)


0.125 0.25 0.5 1 2 4 8

C-peptide 0.5 ng/mLA. Post First Infusion (Censored at Re-Infusion before Visit)


C-peptide < 0.5 ng/mL or Known Graft LossC-peptide >= 0.5 ng/mLMissing data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

Pre Inf 1N=347

Month 6152

Year 1112

C-peptide 0.5 ng/mLA. Post First Infusion (Censored at Re-Infusion before Visit)

Islet After Kidney Recipients


Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

Pre Inf 1N=65

Month 624

Year 116

C-peptide 0.5 ng/mLB. Post Last InfusionIslet Alone Recipients


Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

Pre Inf 1N=347

Month 6314

Year 1298

Year 2266

Year 3216

Year 4155

C-peptide 0.5 ng/mLB. Post Last Infusion



Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

Pre Inf 1N=65

Month 663

Year 159

Year 249

Year 342

Year 4N35

C-peptide 0.3 ng/mLC. Post Last Infusion

With or Without Missing Data

Basal Plasma C-Peptide (ng/mL)Pre Infusion and Post Last Infusion

A. Islet Alone Recipients B. Islet After Kidney Recipients

325 229 78 291 276 239 182 120

(One at pre-inf 2, three at month 6, one at year 1, and one at year 3)Values greater than 6 ng/ml are not displayed or used in boxplot values

Pre Inf 1 Pre Inf 2 Pre Inf 3 Month 6 Year 1 Year 2 Year 3 Year 4

0

1

2

3

4

5

6

ng/m

L

Follow-Up

57 46 11 56 53 39 32 22

(One at year 2)Values greater than 6 ng/ml are not displayed or used in boxplot values


0

1

2

3

4

5

6

ng/m

LFollow-Up

Association of Islet Graft Function with Insulin Independence:Percent Insulin Independent by C-peptide Level Post Last Infusion

Basal Plasma C-Peptide (ng/mL) Pre and Post First Infusion

Insulin Independent Recipients


325 14 36 150 154

(One at month 6 and one at year 1)Values greater than 6 ng/mL are not displayed or used in boxplot values

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

1

2

3

4

5

6

ng/m

L

Follow-Up

57 1 6 25 19


0

1

2

3

4

5

6

ng/m

L

Follow-Up

Basal Plasma C-Peptide (ng/mL) Pre and Post First Infusion

Insulin Dependent Recipients


325 266 280 141 135

(One at day 7)Values greater than 6 ng/mL are not displayed or used in boxplot values


0

1

2

3

4

5

6

ng/m

L

Follow-Up

57 40 46 28 30

(One at day 30)Values greater than 6 ng/mL are not displayed or used in boxplot values


0

1

2

3

4

5

6

ng/m

L

Follow-Up

Percent of Insulin Dependent Recipients with Basal C-Peptide 0.5 ng/mLPost Last Infusion


Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

Pre Inf 1N=347

Month 6131

Year 1147

Year 2148

Year 3122

Year 496

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

Pre Inf 1N=65

Month 622

Year 130

Year 230

Year 333

Year 423

Fasting Plasma Glucose (mg/dL)Pre Infusion and Post Last Infusion


320 242 84 300 281 237 179 116

(Five at pre-inf 1, one at month 6, one at year 1, tw o at year 2, one at year 3 and tw o at year 4)Values greater than 400 mg/dL are not displayed or used in boxplot values


0

100

200

300

400

mg/

dL

Follow-Up

56 48 13 57 54 42 37 23

(Tw o at pre-inf 1, one at year 2 and one at year 4)Values greater than 400 mg/dL are not displayed or used in boxplot values


0

100

200

300

400

mg/

dL

Follow-Up

Fasting Plasma Glucose (mg/dL) Pre and Post First Infusion

Insulin Independent Recipients


56 2 7 24 18

(Tw o at pre-inf 1)Values greater than 400 mg/dL are not displayed or used in boxplot values


0

100

200

300

400

mg/

dLFollow-Up

320 18 38 144 145

(Five at pre-inf 1)Values greater than 400 mg/dL are not displayed or used in boxplot values


0

100

200

300

400

mg/

dL

Follow-Up

Fasting Plasma Glucose (mg/dL) Pre and Post First Infusion

Insulin Dependent Recipients


56 47 47 32 34

(Tw o at pre-inf 1)Values greater than 400 mg/dL are not displayed or used in boxplot values


0

100

200

300

400

mg/

dL

Follow-Up

320 284 285 153 142

(Five at pre-inf 1)Values greater than 400 mg/dL are not displayed or used in boxplot values


0

100

200

300

400

mg/

dL

Follow-Up

Percent of Recipients with Fasting Blood Glucose 126 mg/dLPost Last Infusion by Insulin Status


Insulin Status Independent DependentP

erce

nt o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Infusion 1N=0:56

Month 6N=33:22

Year 1N=23:30

Year 2N=12:29

Year 3N=4:31

Year 4N=3:19

Insulin Status Independent Dependent

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100


Month 6N=171:126

Year 1N=137:142

Year 2N=90:139

Year 3N=54:119

Year 4N=23:91

Composite Outcome (Hypoglycemia and HbA1C) Post Last InfusionA. Islet Alone Recipients

No severe hypoglycemic episodes and HbA1c < 6.5%No severe hypoglycemic episodes and 6.5% <= HbA1c < 7.0%Severe hypoglycemic episode or HbA1c >= 7.0% with detectable fasting c-peptideSevere hypoglycemic episode or HbA1c >= 7.0% without detectable fasting c-peptideMissing data for recipient with islet graft failureOther missing data

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

Pre Infusion 1N=347

Day 30347

Month 6314

Year 1298

Year 2266

Year 3216

Year 4155

Composite Outcome (Hypoglycemia and HbA1C) Post Last InfusionB. Islet After Kidney Recipients

No severe hypoglycemic episodes and HbA1c < 6.5%No severe hypoglycemic episodes and 6.5% <= HbA1c < 7.0%Severe hypoglycemic episode or HbA1c >= 7.0% with detectable fasting c-peptideSevere hypoglycemic episode or HbA1c >= 7.0% without detectable fasting c-peptideMissing data for recipient with islet graft failureOther missing data

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

Pre Infusion 1N=65

Day 3065

Month 663

Year 159

Year 249

Year 342

Year 435

Severe HypoglycemiaA. Post First Infusion (Censored at Re-Infusion before Visit)


No severe hypoglycemic episodesSevere hypoglycemic episodeMissing data for recipient with islet graft failureOther missing data

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=347

Month 6N=152

Year 1N=112

Severe HypoglycemiaB. Post First Infusion (Censored at Re-Infusion before Visit)



Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=65

Month 6N=24

Year 1N=16

Severe HypoglycemiaC. Post Last Infusion Islet Alone Recipients


Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=347

Day 30N=347

Month 6N=314

Year 1N=298

Year 2N=266

Year 3N=216

Year 4N=155

Severe HypoglycemiaD. Post Last Infusion



Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=65

Day 30N=65

Month 6N=63

Year 1N=59

Year 2N=49

Year 3N=42

Year 4N=35

Severe HypoglycemiaE. Post Last Infusion

Islet Alone Recipients with Detectable Fasting C-peptide

Severe hypoglycemic episodeMissing data

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=65

Day 30N=325

Month 6N=278

Year 1N=237

Year 2N=170

Year 3N=114

Year 4N=68

Severe Hypoglycemia

F1. All Islet Alone Recipients with

No Detectable Fasting C-peptide or Known Graft Loss

Post Last Infusion

F2.(Subset of F1): Islet Alone Recipients with

No Detectable Fasting C-peptide or Known Graft Loss and

Known Information on Occurrence of Severe Hypoglycemic Episodes

Post Last Infusion

Severe hypoglycemic episodeMissing dataNo severe hypoglycemic episode

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=260

Day 30N=22

Month 6N=39

Year 1N=54

Year 2N=81

Year 3N=76

Year 4N=67

Severe hypoglycemic episodeNo severe hypoglycemic episode

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=354

Day 30N=20

Month 6N=32

Year 1N=29

Year 2N=38

Year 3N=22

Year 4N=13

Hypoglycemia Status Pre First Infusion and Post Last Infusion


No hypogl ycemi c epi sodesHavi ng epi sodes and awar ePar t i al awar enessHypogl ycemi a unawar enessMi ssi ng dat a f or r eci pi ent wi t h i sl et gr af t f ai l ur eOt her mi ssi ng dat a

Perc

ent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Pr e I nf 1N=412

Mont h 6N=377

Year 1N=357

Year 2N=315

Year 3N=258

Year 4N=190

HbA1C A. Post First Infusion (Censored at Re-Infusion before Visit)


HbA1c < 6.5%6.5% <= HbA1c < 7.0%HbA1c >= 7.0%Missing data for recipient with islet graft failureOther missing data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

Pre Inf 1N=347

Month 6152

Year 1112

HbA1C A. Post First Infusion (Censored at Re-Infusion before Visit)



Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

Pre Inf 1N=65

Month 624

Year 116

HbA1CB. Post Last InfusionIslet Alone Recipients


Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

Pre Inf 1N=347

Month 6314

Year 1298

Year 2266

Year 3216

Year 4155

HbA1CB. Post Last Infusion



Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

Pre Inf 1N=65

Month 663

Year 159

Year 249

Year 342

Year 435

HbA1C (%)Pre Infusion and Post Last Infusion


329 225 82 291 275 231 180 116


2.5

5.0

7.5

10.0

12.5

%

Follow-Up

59 47 12 55 51 42 35 23


2.5

5.0

7.5

10.0

12.5

%

Follow-Up

HbA1C (%) Pre and Post First InfusionInsulin Independent Recipients


59 4 22 17

Pre Inf 1 Day 30 Month 6 Year 1

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

329 29 138 142


2.5

5.0

7.5

10.0

12.5

%

Follow-Up

HbA1C (%) Pre and Post First InfusionInsulin Dependent Recipients


59 24 30 30


2.5

5.0

7.5

10.0

12.5

%

Follow-Up

329 178 145 138


2.5

5.0

7.5

10.0

12.5

%

Follow-Up

Recipients with HbA1C < 6.5%Percent of Post Last Infusion by Insulin Status


Insulin Status Independent Dependent

Perc

ent o

f Rec

ipie

nts

0

10

20

30

40

50

60

70

80

90

100


Month 6N=169:120

Year 1N=135:138

Year 2N=88:137

Year 3N=54:119

Year 4N=23:90

Complications of DiabetesPre First Infusion and Post Last Infusion

All Allograft Recipients with Documented Graft Function

Peripheral Neuropathy Autonomic Neuropathy

DisablingSymptomaticAsymptomaticNone

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=383

Month 6N=263

Year 1N=216

Year 2N=147

Year 3N=96

Year 4N=52

DisablingSymptomaticAsymptomaticNone

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=371

Month 6N=266

Year 1N=216

Year 2N=144

Year 3N=96

Year 4N=53

Complications of Diabetes (continued)Pre First Infusion and Post Last Infusion


Nefropathy Coronary Artery Disease

Stable AllograftESRDMacroalbuminuriaMicroalbuminuriaNone

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=380

Month 6N=280

Year 1N=236

Year 2N=151

Year 3N=93

Year 4N=54

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=386

Month 6N=276

Year 1N=230

Year 2N=154

Year 3N=104

Year 4N=54



Stroke Peripheral Vascular Disease

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=373

Month 6N=275

Year 1N=231

Year 2N=152

Year 3N=104

Year 4N=54

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=367

Month 6N=273

Year 1N=226

Year 2N=152

Year 3N=101

Year 4N=54



Treated Hypertension Foot Ulcers

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=387

Month 6N=295

Year 1N=248

Year 2N=157

Year 3N=104

Year 4N=56

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=347

Month 6N=275

Year 1N=229

Year 2N=151

Year 3N=104

Year 4N=55



Lower Limb Amputation Foot Deformity

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=379

Month 6N=283

Year 1N=237

Year 2N=155

Year 3N=105

Year 4N=58

YesNo

Per

cent

of R

ecip

ient

s0

20

40

60

80

100

Pre Inf 1N=354

Month 6N=278

Year 1N=230

Year 2N=154

Year 3N=105

Year 4N=57



Dysesthesia Orthostatic Hypotension

YesNo

Per

cent

of R

ecip

ient

s0

20

40

60

80

100

Pre Inf 1N=316

Month 6N=246

Year 1N=212

Year 2N=133

Year 3N=97

Year 4N=53

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=350

Month 6N=262

Year 1N=219

Year 2N=145

Year 3N=99

Year 4N=51



Gastroparesis Constipation

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=342

Month 6N=267

Year 1N=223

Year 2N=140

Year 3N=99

Year 4N=51

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=340

Month 6N=270

Year 1N=228

Year 2N=147

Year 3N=99

Year 4N=51



Diabetic Diarrhea Fecal Incontinence

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=345

Month 6N=257

Year 1N=220

Year 2N=145

Year 3N=99

Year 4N=52

YesNo

Per

cent

of R

ecip

ient

s0

20

40

60

80

100

Pre Inf 1N=342

Month 6N=268

Year 1N=228

Year 2N=149

Year 3N=100

Year 4N=53



Diabetic Bladder Dysfunction Sexual Dysfunction

YesNo

Per

cent

of R

ecip

ient

s0

20

40

60

80

100

Pre Inf 1N=316

Month 6N=233

Year 1N=200

Year 2N=124

Year 3N=85

Year 4N=44

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=341

Month 6N=268

Year 1N=226

Year 2N=144

Year 3N=99

Year 4N=52



Retinopathy Diabetic Macular Edema

SevereModerateMildNone

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=352

Month 6N=238

Year 1N=189

Year 2N=114

Year 3N=83

Year 4N=38

ProliferativeNon ProliferativeNone

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=376

Month 6N=239

Year 1N=190

Year 2N=114

Year 3N=80

Year 4N=43



Laser Photocoagulation Surgery for

Proliferative Retinopathy

Laser Photocoagulation Surgery for

Diabetic Macular Edema

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=372

Month 6N=287

Year 1N=241

Year 2N=153

Year 3N=105

Year 4N=55

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=357

Month 6N=287

Year 1N=241

Year 2N=153

Year 3N=105

Year 4N=54



Vtirectomy Other Eye Surgery

YesNo

Per

cent

of R

ecip

ient

s0

20

40

60

80

100

Pre Inf 1N=366

Month 6N=287

Year 1N=241

Year 2N=154

Year 3N=105

Year 4N=54

YesNo

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Pre Inf 1N=379

Month 6N=287

Year 1N=241

Year 2N=153

Year 3N=105

Year 4N=54

Chapter 6: Liver, Kidney, Lipid and PRA Effects

ALT (IU/L) Pre Infusion and Post Last Infusion


57 49 13 52 46 34 27 15

(One at pre-inf 2, one at month 6, and one at year 2)Values greater than 150 IU/L are not displayed or used in boxplot values


0

25

50

75

100

125

150

IU/L

Follow-Up

307 211 70 234 193 128 79 45

(Tw o at pre-inf 2, one at month 6, one at year 1, and one at year 2)Values greater than 150 IU/L are not displayed or used in boxplot values


0

25

50

75

100

125

150

IU/L

Follow-Up

AST (IU/L) Pre Infusion and Post Last Infusion


58 49 12 52 46 34 27 15

(One at month 6, and one at year 2)Values greater than 120 IU/L are not displayed


0

20

40

60

80

100

120

IU/L

Follow-Up

320 233 77 272 229 148 95 51

(One at pre-inf 1, one at pre-inf 2, one at month 6, one at year 1, and one at year 2)Values greater than 120 IU/L are not displayed


0

20

40

60

80

100

120

IU/L

Follow-Up

Alkaline Phosphatase (IU/L) Pre Infusion and Post Last Infusion


317 229 75 260 229 144 95 50

(Tw o at pre-inf 2, one at month 6, one at year 1, and one at year 2)Values greater than 350 IU/L are not displayed


0

50

100

150

200

250

300

350

IU/L

Follow-Up

56 49 12 48 46 34 27 15

(Four at pre-inf 1, four at pre-inf 2, tw o at year 1, and one at year 2)Values greater than 350 IU/L are not displayed


0

50

100

150

200

250

300

350

IU/L

Follow-Up

Total Bilirubin (mg/dL) Pre Infusion and Post Last Infusion


57 47 13 45 45 34 26 13


0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

mg/

dLFollow-Up

319 221 75 251 214 145 94 48

(One at pre-inf 1 and one at year 1)Values greater than 3.5 mg/dL are not displayed


0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

mg/

dL

Follow-Up

Total Cholesterol (mg/dL) Pre Infusion and Post Last Infusion


56 39 9 48 43 34 28 15


0

50

100

150

200

250

300

350

mg/

dL

Follow-Up

327 196 69 248 230 152 98 49


0

50

100

150

200

250

300

350

mg/

dL

Follow-Up

HDL (mg/dL) Pre Infusion and Post Last Infusion


49 28 5 35 34 27 24 11


0

50

100

150

200

mg/

dL

Follow-Up

319 179 59 228 218 139 93 47


0

50

100

150

200

mg/

dL

Follow-Up

LDL (mg/dL) Pre Infusion and Post Last Infusion


47 28 5 35 34 27 24 11


0

50

100

150

200

250

300

mg/

dL

Follow-Up

313 178 57 225 214 138 92 47


0

50

100

150

200

250

300

mg/

dL

Follow-Up

Triglycerides (mg/dL) Pre Infusion and Post Last Infusion


55 39 9 48 43 34 27 14


0

50

100

150

200

250

300

350

400

450

mg/

dLFollow-Up

327 194 69 246 229 150 98 50


0

50

100

150

200

250

300

350

400

450

mg/

dL

Follow-Up

Serum Creatinine (mg/dL) Pre Infusion and Post Last Infusion


62 48 14 54 49 34 28 16

(Tw o at pre-inf 1, one at month 6 and one at year 2)Values greater than 4.0 mg/dL are not displayed


0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

mg/

dLFollow-Up

338 234 78 280 243 169 104 56


0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

mg/

dL

Follow-Up

Percent of Recipients with a 30% Increase in Serum Creatinineat Each Follow-up Time Point


>=30% Increase In Serum Creatinine<30% Increase In Serum Creatinine

Per

cent

of R

ecip

ient

s0

20

40

60

80

100

Month 6N=52

Year 1N=47

Year 2N=34

Year 3N=27

Year 4N=15

>=30% Increase In Serum Creatinine<30% Increase In Serum Creatinine

Per

cent

of R

ecip

ient

s

0

20

40

60

80

100

Month 6N=277

Year 1N=240

Year 2N=167

Year 3N=103

Year 4N=55

Cockgroft-Gault Calculated Creatinine Clearance (mL/min/1.73m2)Pre Infusion and Post Last Infusion


42 18 5 22 27 19 15 10


0

50

100

150

200

250

mL/

min

/1.7

3m2

Follow-Up

271 114 35 146 146 66 39 19


0

50

100

150

200

250

mL/

min

/1.7

3m2

Follow-Up

“Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Estimated GFR (mL/min/1.73m2)Pre Infusion and Post Last Infusion


60 47 14 53 48 34 28 16


0

30

60

90

120

150

180

ml/m

in/1

.73

m2

Follow-Up

338 234 78 280 243 169 104 56

(One at pre-inf 1 and one at pre-inf 3)Values greater than 180 ml/min/1.73 m2 are not displayed or used in boxplot values


0

30

60

90

120

150

180

ml/m

in/1

.73

m2

Follow-Up

Class I PRA (%)Pre Infusion and Post Last Infusion


303 206 73 200 174 135 98 63


0

10

20

30

40

50

60

70

80

90

100

%

Follow-Up

% Change in Class I PRA from Pre First InfusionPre Subsequent Infusion and Post Last Infusion


203 71 199 173 134 96 63

(One at pre-inf 3 and one at year 1)Values less than -25 are not displayed

Pre Inf 2 Month 6 Year 2 Year 4

-25

0

25

50

75

100

Cha

nge

from

Pre

Infu

sion

1

Follow-Up

Class I PRA Post Last InfusionIslet Alone Recipients with Complete Graft Loss

11 15 26 18 9

Month 6 Year 1 Year 2 Year 3 Year 4

0

10

20

30

40

50

60

70

80

90

100

%

Follow-Up

Class I PRA Post Last InfusionIslet Alone Recipients without Complete Graft Loss

189 159 109 80 54


0

10

20

30

40

50

60

70

80

90

100

%

Follow-Up

Class I PRA Post Last InfusionNon-Immunosupressed Islet Alone Recipients

4 7 12 7 3


0

10

20

30

40

50

60

70

80

90

100

%

Follow-Up

Class I PRA Post Last InfusionImmunosupressed Islet Alone Recipients

191 164 119 87 57


0

10

20

30

40

50

60

70

80

90

100

%

Follow-Up

Chapter 7: Adverse Events

Percent of Recipients with an Adverse Event (AE) or Serious Adverse Event (SAE)in Year 1 Post First Infusion

Total Number of Adverse Events and Serious Adverse Eventsin Year 1 Post First Infusion

IA: Incidence of Post-Transplant Adverse Events Related to Infusion Procedure

IAK: Incidence of Post-Transplant Adverse Events Related to Infusion Procedure

IA: Incidence of Post-Transplant Adverse Events Related to Immunosupression Therapy Follow-up Based on Completed Scheduled Visits

IAK: Incidence of Post-Transplant Adverse Events Related to Immunosupression Therapy Follow-up based on completed scheduled visits

Percent of Recipients with a Serious Adverse Eventin Year 1 Post First Infusion by Year of First Infusion


Any SAESAE related to either the infusion procedure or immunosuppressionSAE related to the infusion procedureSAE related to immunosuppression

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

Year of First Infusion1999-2000N=19

2001-2002N=115

2003-2004N=100

2005-2006N=111

2007-2008N=67

Serious Adverse Event Criteria by Relatedness to Islet Infusion or Immunosuppression

Outcome of Serious Adverse Events by Relatedness to Islet Infusion or Immunosuppression

Serious Adverse Events MedDRA System/Organ Classby Relatedness to Islet Infusion or Immunosuppression

Serious Adverse Events MedDRA System/Organ Classby Relatedness to Islet Infusion or Immunosuppression (continued)

Most Common Serious Adverse EventsMedDRA Preferred Term


Most Common Serious Adverse Events MedDRA Preferred Term


Most Common Serious Adverse Events ReportedWithin One Year of Any Infusion

MedDRA Preferred Term All Allograft Recipients

Most Common Serious Adverse Events ReportedMore than One Year after Any Infusion

MedDRA Preferred Term All Allograft Recipients

Listing of Reported NeoplasmsAll Allograft Recipients

Listing of Reported Neoplasms (continued)All Allograft Recipients

Listing of Reported Neoplasms (continued)All Allograft Recipients

Listing of Reported Hemorrhages and Portal Vein ThrombosesAll Allograft Recipients

Listing of Reported Hemorrhages and Portal Vein Thromboses (continued)All Allograft Recipients



Number of Days Hospitalized at Infusion (from Admission to Discharge)by Infusion SequenceIslet Alone Recipients

330 233 75

(Three at infusion 1 and one at infusion 3)Values greater than 20 days are not displayed

1 2 3

0

5

10

15

20

Num

ber o

f Day

s

Infusion Sequence

Number of Days Hospitalized at Infusion (from Admission to Discharge)by Infusion Sequence


62 47 13

(Three at infusion 1 and one at infusion 3)Values greater than 20 days are not displayed

1 2 3

0

5

10

15

20

Num

ber o

f Day

s

Infusion Sequence

Hospitalization Experienced Post Last Infusion by Total Number of Infusions ReceivedIslet Alone Recipients

Hospitalization Experienced Post Last Infusion by Total Number of Infusions ReceivedIslet After Kidney Recipients

Chapter 8: Registry Data Quality Review

Expected and Submitted Forms by Infusion Sequence

Expected and Submitted Follow-Up Forms Post Last infusionAll Allograft Recipients

Extent of Follow-Up Post Last InfusionAll Allograft Recipients

Appendices

CITR Coordinating Center(July 2008 – July 2009)

PI: Franca Benedicty Barton

Co-PI: Donald Stablein

Yamini Babu

Ruth Danoff

Jodi DeStefano

Andrew Heitman

Krista Huang

Steve Wease

Tina Winters

Islet Transplant Centers

Baylor College of Medicine/

The Methodist Hospital

Houston, Texas, USA

PI: John A. Goss

Baylor Regional Transplant Institute

Dallas, Texas, USA

PI: Marlon Levy

Benaroya Research Institute

Seattle, Washington, USA

PI: Carla Greenbaum

Carolinas Medical Center

Charlotte, North Carolina, USA

PI: Paul Gores

Center for Islet Transplantation at Harvard

Medical School

Boston, Massachusetts, USA

PI: Enrico Cagliero

Columbia University

New York, New York, USA

PI: Mark A. Hardy

Emory Transplant Center

Atlanta, Georgia, USA

PI: Mark Rigby

GenevaGRAGIL Network

Geneva, Switzerland

PI: Thierry Berney

Lille University Hospital

Lille Cedex, France

PI: Francois Pattou

Mayo Clinic

Rochester, Minnesota, USA

PI: Yogish Kudva

NIH Clinical Transplant Center

Bethesda, Maryland, USA

PI: David Harlan

Northwestern University

Chicago, Illinois, USA

PI: Dixon Kaufman

San Raffaele Institute

Milan, Italy

PI: Antonio Secchi

Scripps Health

La Jolla, California, USA

PI: Christopher Marsh

Southern California Islet Consortium (SCIC)

Duarte, California, USA

PI: Fouad Kandeel

St. Vincent’s Institute

Fitzroy, Victoria, Australia

PI: Tom Kay

Swedish Medical Center

Seattle, Washington, USA

PI: William Marks

Toronto General Hospital

Toronto, Ontario, CANADA

PI: Mark Cattral

The University of Tennessee, Memphis

Memphis, Tennessee, USA

PI: A. Osama Gaber

UMass Memorial Hospital

Worcester, Massachusetts, USA

PI: Aldo Rossini

University of Alabama

Birmingham, Alabama, USA

PI: Juan Luis Contreras

University of Alberta

Edmonton, Alberta, CANADA

PI: A. M. James Shapiro

Co-PI: Peter Senior

Parastoo Dinyari

University of California,

San Francisco

San Francisco, California, USA

PI: Peter Stock

Co-PI: Andrew Posselt

University of Chicago


PI: Marc Garfinkel

University of Colorado Health Sciences

Center

Auora, Colorado, USA

PI: Alexander Wiseman

University of Illinois, Chicago


PI: Jose Oberholzer

Co-PI: Enrico Benedetti

Co-PI: James Bui

Co-PI: Charles Owens

University of Miami

Miami, Florida, USA

PI: Rodolfo Alejandro

Co-PI: Camillo Ricordi

University of Minnesota

Minneapolis, Minnesota, USA

PI: Bernhard J. Hering

University of Nebraska

Omaha, Nebraska, USA

PI: R. Brian Stevens

University of Pennsylvania

Philadelphia, Pennsylvania, USA

PI: Ali Naji

University of Virginia

Charlottesville, Virginia, USA

PI: Kenneth Brayman

University of Wisconsin

Madison, Wisconsin, USA

PI: Jon Odorico

Virginia Commonwealth University

Richmond, Virginia, USA

PI: Adrian Cotterell

University of Pennsylvania

Washington University,

St. Louis

St. Louis, Missouri, USA

PI: Niraj Desai

Westmead Hospital

Wentworthville, NSW, Australia

PI: Philip Oconnell

CITR Committees

Scientific Advisory Committee (SAC)

Compliance Committee (2008)

Data Elements Committee (2008)

Publications/Presentations Committee (2008)

Transplant Coordinators’/Data Managers’ Committee (2008)

CITR Scientific Advisory Committee (SAC)Chair: Bernhard J. Hering

Michael Appel

Franca Benedicty Barton

Michael Cecka

Philip E. Cryer

Olle Korsgren

Maureen McBride

Jerry P. Palmer

Camillo Ricordi

Gordon Weir

CITR Compliance Committee (2008)

Chair: Fouad Kandeel

Michael Appel

Parastoo Dinyari

Albert Hwa

Carol Kramer

Joan Martellotto

Violetta Raverdi

Marti Sears

Elyse Stuart

CITR Data Elements Committee (2008)

Chair: Marti Sears

David Baidal

Enrico Cagliero

Marc Garfinkel

Fouad Kandeel

Dixon Kaufman

Robert Ketchum

Francois Pattou

David Sutherland

CITR Publications/Presentations Committee (2008)

Chair: Rodolfo Alejandro

Michael Appel

Nancy Bridges

Shari Messinger Cayetano

Brian Flanagan

Elizabeth Holbrook

Robert Ketchum

Bashoo Naziruddin

Craig Smith

CITR Transplant Coordinators’/Data Managers’ Committee (2008)

Chair: Parastoo Dinyari

Jarrett Anderson

David Baidal

LeAnn Batterson

Meyer Belzer

Elsa Boely

Jane Fasbender

Courtney Garbee

Susan George

Debbie Grice

Darrell Grimes

Jeannette Hacker

Celia Hartigan

Elizabeth Holbrook

Nancy Radke

Violeta Raverdy

Marilyn Reeve

Kristi Schneider

Marti Sears

Jill Sheedy

KD Shiang

Elyse Stuart

Pat Swanson

Heather Turgeon

Patricia Wilson

Dona Winborne

Piotr Witkowski

Robin Jevne

Jenny Joseph

Debra Kemp

Mark Lockwood

Eileen Markmann

Joan Martellotto

Marli McCulloch-Olson

Joan McElroy

Melissa McGraw

Suzanne Miller

Bashoo Naziruddin

Lori Otken

Maral Palanjian

Jamen Parkey

CITR AllograftsRecipients with C-Peptide ≥ 0.3 Pre-Infusion

Documents

CITR Annual Report Exhibits