CITR Annual Report Exhibits Collaborative Islet Transplant Registry (CITR) 2008 Annual Report...

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CITR Annual Report ExhibitsCollaborative Islet Transplant Registry (CITR)

2008 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, 2008

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 1999-2007

A - CITR Centers with at least one islet allograft infusion procedure conducted in 2007C - CITR Centers with no islet allograft infusions in 2007D - CITR Coordinating Center

Number of Islet Transplantation Centers Performing Islet Allografts per Year and Number with

Data Entered in CITR Database All North American Islet Transplant Centers 1999-2007

All North American Centers Performing Islet Allografts (N=31)CITR-Participating Centers with Data Entered (N=25)

6

3

9

6

16

11

14

11

20

16

23

19

16

14

10

8

Num

ber

of C

ente

rs

0

5

10

15

20

25

1999-2000 2001 2002 2003 2004 2005 2006 2007

Total Number of Islet Transplant 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 1999-2007

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=378)All North American CITR Recipients (N=339)Recipients with Detailed Data Reported to CITR (N=296)

31 31

16

45 44

35

82

75

69

45

3836

53

4441

64

55 53

3732

30

21 2016

Num

ber

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

1999-2000 2001 2002 2003 2004 2005 2006 2007

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

CITR-Participating North American Islet Transplant Centers 1999-2007

All Infusions for North American Recipients (N=717)All Infusions for North American CITR Recipients (N=637)Infusions with Data Reported to CITR (N=570)

50 50

32

65 64

49

142

132

119

106

9185

110

9387

124

109 106

78

64 62

4234

30

Num

ber

of P

roce

dure

s

0

20

40

60

80

100

120

140

160

1999-2000 2001 2002 2003 2004 2005 2006 2007

Total Number (N=649) of Islet Allograft Infusion Procedures Conducted and Entered in CITR Database, by Year and Infusion Procedure Number:

CITR-Participating North American and International Centers, 1999-2007

First infusionSecond InfusionThird InfusionFourth Infusion

39

49

119

96100

125

79

38

4

Num

ber

of Is

let In

fusio

ns

0

15

30

45

60

75

90

105

120

135

1999-2000 2001 2002 2003 2004 2005 2006 2007 2008

Total Number (N=649) of Islet Allograft Infusion Procedures Per Recipient:

CITR-Participating North American and International Centers, 1999-2007

Islet Alone RecipientsIslet After Kidney Recipients

84

164

71

6

Num

ber

of R

ecip

ient

s

0

20

40

60

80

100

120

140

160

180

Total Number of Infusions Received

1 2 3 4

Total Number (N=712) of Deceased Donors per Islet Allograft Infusion Procedure:

CITR-Participating North American and International Centers, 1999-2007

589

57

3

Num

ber

of Is

let A

llogr

aft I

nfus

ions

0

50

100

150

200

250

300

350

400

450

500

550

600

Total Number of Donors Received

1 2 3

Islet Alone and Islet After Kidney Recipients:CITR-Participating North American and International Centers,

1999-2007

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 Diabetes Characteristics at First Infusion (continued)

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

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)

Pancreas Procurement and Islet Processing (continued)

Cold Ischemia Information

Islet Equivalents and Timing of Count

Islet Product Characterization

Differences in Islet Characteristics by Pancreas Preservation MethodUnivariate Analysis

Significant Relationships between Islet Outcomes and Categorical Predictors

Univariate Analysis

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

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

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

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

Islet Product and Infusion Characteristics by Infusion Sequence

Pre Infusion Portal Pressure by Infusion Sequence

Peak Portal Pressure by Infusion Sequence

Closure Portal Pressure by Infusion Sequence

Change from Pre Infusion to Closure Portal Pressure by Infusion Sequence

Change from Pre Infusion to Peak Portal Pressure by Infusion Sequence

Cell Volume Infused per Infusion by Infusion Year

IEQs Infused per Infusion by Infusion Year

Chapter 4: Immunosuppression and other Medications

Immunosuppression Regimen at Time of First Infusion

Immunosuppression Regimen at Time of First Infusion (continued)

Antibodies Used Peri First Infusion for Induction Therapy

Allograft Type

Islet AloneIslet After

Kidney

N % N %

Total 263 100.0

43 100.0

Daclizumab Alone 163 62.0

34 79.1

Daclizumab + Anti-Thymocyte Globulin 5 1.9 - 0.0

Daclizumab + Anti-Thymocyte Globulin + Etanercept 8 3.0 - 0.0

Daclizumab + Infliximab 18 6.8 2 4.7

Daclizumab + Etanercept 9 3.4 3 7.0

Daclizumab + Efalizumab 1 0.4 - 0.0

Alemtuzumab Alone 14 5.3 - 0.0

Alemtuzumab + Etanercept 5 1.9 - 0.0

Alemtuzumab + Infliximab 1 0.4 - 0.0

Anti-Thymocyte Globulin Alone 5 1.9 1 2.3

Anti-Thymocyte Globulin + Etanercept 9 3.4 2 4.7

Anti-Thymocyte Globulin + Efalizumab 5 1.9 - 0.0

Basiliximab Alone 1 0.4 0 0.0

Basiliximab + Etanercept 11 4.2 1 2.3

hOKT3γ-1(Ala-Ala) Alone 8 3.0 - 0.0

Antibody Dosing at Time of Infusion by Infusion Sequence

Immunosuppression Dosing (mg/day) at Time of Infusion by Infusion Sequence

Immunosuppression Therapy Use at Specific Times Post Last Infusion Allograft Recipients without Reported Graft

Failure at the Time of Follow-Up

Immunosuppression Therapy Use at Specific Times Post Last Infusion Allograft Recipients without Reported Graft Failure

at the Time of Follow-Up (continued)

Immunosuppression Dosing Post Last Infusion

Immunosuppression Dosing Post Last Infusion (continued)

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

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

Anti-Hypertensive Medications Pre Infusion and Post Last Infusion

All Allograft Recipients

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

All Allograft Recipients

Lipid Lowering Medications Pre Infusion and Post Last Infusion

All Allograft Recipients

Total Number of Lipid Lowering MedicationsPre Infusion and Post Last Infusion

All Allograft Recipients

Adjunctive Therapy Used at Time of First InfusionAll Allograft Recipients

Adjunctive Therapy Post Last InfusionAll Allograft Recipients

Follow Up Visit

Month 6 Year 1 Year 2 Year 3

N% of

known N% of

known N% of

known N% of

known

Total

246 100.0 217 100.0 150 100.0 92 100.0

Pentoxifylline 31 12.6 1 0.5 - 0.0 - 0.0

Metformin 11 4.5 7 3.2 6 4.0 4 4.3

Exenatide 7 2.8 8 3.7 4 2.7 5 5.4

Rosiglitazone 4 1.6 5 2.3 3 2.0 3 3.3

Pioglitazone 2 0.8 1 0.5 1 0.7 - 0.0

Acarbose 3 1.2 2 0.9 1 0.7 - 0.0

Repaglinide 3 1.2 1 0.5 3 2.0 4 4.3

Sitagliptin 1 0.4 1 0.5 - 0.0 - 0.0

Gliclazide - 0.0 - 0.0 - 0.0 1 1.1

Chromium picolinate 2 0.8 1 0.5 1 0.7 - 0.0

Iron 5 2.0 7 3.2 6 4.0 - 0.0

Vitamins 44 17.9 35 16.1 9 6.0 - 0.0

Chapter 5: Graft Function

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

Post First InfusionA. Islet Alone Recipients

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=279

Day 75N=279

Month 6N=275

Year 1N=269

Year 3*N=198

*Year 3 status regardless of re-infusion

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

Post First Infusion B. Islet After Kidney Recipients

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=46

Day 75N=46

Month 6N=45

Year 1N=43

Year 3*N=36

*Year 3 status regardless of re-infusion

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

Month 6N=269

Year 1N=260

Year 2N=220

Year 3N=160

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

Post Last InfusionB. Islet After Kidney 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

Month 6N=44

Year 1N=40

Year 2N=35

Year 3N=31

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

Post Last Infusion by Total Number of Infusions ReceivedIslet Alone Recipients

A. Recipients of 1 Infusion

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

Month 6N=74

Year 1N=69

Year 2N=57

Year 3N=39

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

Post Last Infusion by Total Number of Infusions ReceivedIslet Alone Recipients

B. Recipients of 2 Infusions

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

Month 6N=131

Year 1N=129

Year 2N=112

Year 3N=82

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

Post Last Infusion by Total Number of Infusions ReceivedIslet Alone Recipients

C. Recipients of 3 Infusions

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

Month 6N=64

Year 1N=62

Year 2N=51

Year 3N=39

Prevalence of Insulin Independence Post Last InfusionIslet Alone Recipients

Best Case Reported Worst Case

Perc

ent In

sulin

Independent

0

10

20

30

40

50

60

70

Months Post Last Infusion

0 3 6 9 12 15 18 21 24 27 30 33 36

Month 0 6 12 18 24 30 36

N Expected 279 269 260 245 220 194 160

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

Islet Alone Recipients

Total Number of Infusions Received One Two Three

Percent In

sulin Independent

0

10

20

30

40

50

60

70

Months Post Last Infusion

0 3 6 9 12 15 18 21 24 27 30 33 36

Month 0 6 12 18 24 30 36

N 1 Infusion 77 56 52 47 44 35 33

N 2 Infusions 125 121 111 95 91 71 58

N 3 Infusions 58 55 51 47 39 32 26

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

Islet Alone Recipients

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=279

Month 6N=130

Year 1N=94

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

Islet After Kidney Recipients

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=46

Month 6N=14

Year 1N=9

HbA1C

B. Post Last InfusionIslet Alone Recipients

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=279

Month 6N=269

Year 1N=260

Year 2N=220

Year 3N=160

HbA1C

B. Post Last InfusionIslet After Kidney Recipients

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=46

Month 6N=44

Year 1N=40

Year 2N=35

Year 3N=31

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

Islet Alone Recipients

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=279

Month 6N=130

Year 1N=94

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

Islet After Kidney Recipients

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=46

Month 6N=14

Year 1N=9

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

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=279

Month 6N=269

Year 1N=260

Year 2N=220

Year 3N=160

C-peptide 0.5 ng/mLB. Post Last Infusion

Islet After Kidney Recipients

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=46

Month 6N=44

Year 1N=40

Year 2N=35

Year 3N=31

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

Islet Alone Recipients

No severe hypoglycemic episodesSevere hypoglycemic episodeMissing 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

90

100

Pre Inf 1N=279

Month 6N=130

Year 1N=94

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

Islet After Kidney Recipients

No severe hypoglycemic episodesSevere hypoglycemic episodeMissing 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

90

100

Pre Inf 1N=46

Month 6N=14

Year 1N=9

Severe HypoglycemiaC. Post Last Infusion Islet Alone Recipients

No severe hypoglycemic episodesSevere hypoglycemic episodeMissing 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

90

100

Pre Inf 1N=279

Day 30N=279

Month 6N=269

Year 1N=260

Year 2N=220

Year 3N=160

Severe HypoglycemiaD. Post Last Infusion

Islet After Kidney Recipients

No severe hypoglycemic episodesSevere hypoglycemic episodeMissing 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

90

100

Pre Inf 1N=46

Day 30N=46

Month 6N=44

Year 1N=40

Year 2N=35

Year 3N=31

Severe HypoglycemiaE. Post Last Infusion

Islet Alone Recipients with Detectable Fasting C-peptide

Severe hypoglycemic episodeMissing data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=57

Day 30N=215

Month 6N=188

Year 1N=162

Year 2N=89

Year 3N=58

Severe HypoglycemiaF1. Post Last Infusion

All Islet Alone Recipients with No Detectable Fasting C-peptide or Known Graft Loss

Severe hypoglycemic episodeMissing dataNo severe hypoglycemic episode

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=201

Day 30N=13

Month 6N=28

Year 1N=45

Year 2N=61

Year 3N=54

Severe HypoglycemiaF2. Post Last Infusion

Islet Alone Recipients with No Detectable Fasting C-peptide or Known Graft Loss and Known Information on Occurrence

of Severe Hypoglycemic Episodes

Severe hypoglycemic episodeNo severe hypoglycemic episode

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=199

Day 30N=12

Month 6N=22

Year 1N=22

Year 2N=21

Year 3N=10

Hypoglycemia Status Pre First Infusion and Post Last Infusion

All Allograft Recipients

No hypoglycemic episodesHaving episodes and awarePartial awarenessHypoglycemia unawarenessMissing data for recipient with islet graft failureOther missing data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Pre Inf 1N=325

Month 6N=313

Year 1N=300

Year 2N=255

Year 3N=191

Graft Loss or Dysfunction Post Last InfusionA. Islet Alone Recipients

Complete Graft FailureMissing DataGraft Function

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Day 30N=279

Month 6N=269

Year 1N=260

Year 2N=220

Year 3N=160

Graft Loss or Dysfunction Post Last InfusionB. Islet After Kidney Recipients

Complete Graft FailureMissing DataGraft Function

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Day 30N=46

Month 6N=44

Year 1N=40

Year 2N=35

Year 3N=31

Persistence of Islet Graft Function (IA, IAK) A. Reported Data

Sur

viva

l Dis

trib

utio

n F

unct

ion

0.00

0.25

0.50

0.75

1.00

months

0 5 10 15 20 25 30 35 40

STRATA: typeoftran=IA Censored typeoftran=IAtypeoftran=IAK Censored typeoftran=IAK

Timepoint 0 6 12 18 24 30 36

N Islet Alone 279 211 169 137 102 74 61

N Islet After Kidney 46 29 23 18 15 13 9

Persistence of Islet Graft Function (IA, IAK)B. Participants with More than Two Years of Missing Follow-

Up Imputed as Graft Failure at Three Months after Last Follow-Up

Sur

viva

l Dis

trib

utio

n F

unct

ion

0.00

0.25

0.50

0.75

1.00

months

0 5 10 15 20 25 30 35 40

STRATA: typeoftran=IA Censored typeoftran=IAtypeoftran=IAK Censored typeoftran=IAK

Timepoint 0 6 12 18 24 30 36

N Islet Alone 279 214 174 138 106 74 61

N Islet After Kidney 46 30 25 18 16 13 10

Persistence of Islet Graft Function by Ever Achieving Insulin Independence

Islet Alone RecipientsNot Censored at Re-Infusion

Sur

viva

l Dis

trib

utio

n F

unct

ion

0.00

0.25

0.50

0.75

1.00

months

0 5 10 15 20 25 30 35 40

STRATA: EVER=Achieved insulin independenceCensored EVER=Achieved insulin independenceEVER=Never achieved insulin independenceCensored EVER=Never achieved insulin independence

Timepoint 0 6 12 18 24 30 36

N Achieved Insulin Independence 177 154 125 109 79 66 52

N Did Not Achieve Insulin Independence 102 63 48 36 23 11 7

Achievement of Insulin IndependenceA. All Allograft Recipients

Post First Infusion (Not Censored at Re-Infusion)

Type of Allograft Islet AloneIslet After Kidney

Pe

rce

nt

of

Re

cip

ien

ts

0

10

20

30

40

50

60

70

80

90

100

Months Post First Infusion

0 6 12 18 24 30 36

Timepoint 0 6 12 18 24 30 36

N Islet Alone 279 113 73 58 46 29 23

N Islet After Kidney 46 15 9 9 9 5 4

Achievement of Insulin IndependenceB. Islet Alone Recipients

Post First Infusion (Censored at Re-Infusion)

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Months Post First Infusion

0 2 4 6 8 10

N 279 144 91 65 50 37

Achievement of Insulin IndependenceC. Islet Alone Recipients

Post Second Infusion (Recipients Not Insulin Independent after First Infusion, Censored

at Third Infusion)

Percent o

f R

ecip

ients

0

10

20

30

40

50

60

70

80

90

100

Months Post Second Infusion

0 2 4 6 8 10

N 201 75 57 49 44 39

Achievement of Insulin IndependenceD. Islet Alone Recipients

Post Third Infusion (Recipients Not Insulin Independent after Second Infusion,

Censored at Fourth Infusion)

Percent of R

ecip

ients

0

10

20

30

40

50

60

70

80

90

100

Months Post Third Infusion

0 2 4 6 8 10

N 64 26 19 18 18 16

Persistence of Insulin Independence and Persistence of Graft Function

Islet Alone Recipients Achieving Insulin IndependenceNot Censored at Re-Infusion

100

75

25

0

Months Post First Achieving Insulin Independence Persistence of Graft Function Persistence of Insulin Independence

50

Timepoint0 6 12 18 24

3036

N Without Graft Loss 177 154 125 109 79 66 52

N Insulin Independent 177 126 102 80 55 37 22

Per

cent

of

Rec

ipie

nts

Persistence of Insulin IndependenceBy Total Number of Infusions Given Prior to

Achievement of Insulin IndependenceIslet Alone Recipients Achieving Insulin Independence

Timepoint0 6 12 18 24

3036

N 1 Infusion 56 36 27 23 16 9 6

N 2 Infusions 92 66 55 41 31 21 12

N 3 Infusions 28 24 20 16 8 7 4

Per

cent

of

Rec

ipie

nts

Months Post First Achieving Insulin Independence Infusions = 1 Infusions = 2 Infusions = 3

100

75

50

25

0

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

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Pre Infusion 1N=279

Day 30N=279

Month 6N=269

Year 1N=260

Year 2N=220

Year 3N=160

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

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

Pre Infusion 1N=46

Day 30N=46

Month 6N=44

Year 1N=40

Year 2N=35

Year 3N=31

Average Daily Insulin (Units) Taken By Recipients on Insulin

Baseline and Post Last InfusionA. Islet Alone Recipients

267 59 61 51 38

Pre Infusion 1 Month 6 Year 1 Year 2 Year 3

0

20

40

60

80

100

Ave

rage

Dai

ly I

nsul

in U

se (

Uni

ts)

Follow-Up

Average Daily Insulin (Units) Taken By Recipients on Insulin

Baseline and Post Last InfusionB. Islet After Kidney Recipients

43 11 13 14 13

Pre Infusion 1 Month 6 Year 1 Year 2 Year 3

0.0

20.0

40.0

60.0

80.0

100.0

Avera

ge D

aily

Insulin

Use (

Units)

Follow-Up

Average Daily Insulin (Units/Kg) Taken By Recipients on Insulin

Baseline and Post Last InfusionA. Islet Alone Recipients

262 55 53 41 32

Pre Infusion 1 Month 6 Year 1 Year 2 Year 3

0

0.2

0.4

0.6

0.8

1.0

1.2

Ave

rage

Dai

ly I

nsul

in U

se (

Uni

ts/k

g)

Follow-Up

Average Daily Insulin (Units/Kg) Taken By Recipients on Insulin

Baseline and Post Last InfusionB. Islet After Kidney Recipients

42 9 9 12 10

Pre Infusion 1 Month 6 Year 1 Year 2 Year 3

0

0.2

0.4

0.6

0.8

1.0

1.2

Ave

rage

Dai

ly I

nsul

in U

se (

Uni

ts/k

g)

Follow-Up

Percent of Baseline Insulin Used By Recipients on Insulin

Follow-Up Post Last InfusionA. Islet Alone Recipients

57 59 50 36

Month 6 Year 1 Year 2 Year 3

0

50

100

150

Per

cent

of

Bas

elin

e In

sulin

Follow-Up

Percent of Baseline Insulin Used By Recipients on Insulin

Follow-Up Post Last InfusionB. Islet After Kidney Recipients

11 13 14 12

Month 6 Year 1 Year 2 Year 3

0

25

50

75

100

125

Per

cent

of

Bas

elin

e In

sulin

Follow-Up

Percent of Baseline Insulin at Follow-Up Post Last InfusionIslet Alone Recipients who Achieved then Lost

Insulin Independence

14 30 35 30

Month 6 Year 1 Year 2 Year 3

0

15

30

45

60

75

90

105

120

135

150

Per

cent

of

Bas

elin

e In

sulin

Follow-Up

Percent of Baseline Insulin at Follow-Up Post Last InfusionIslet Alone Recipients

Never Achieving Insulin Independence

42 29 15 6

Month 6 Year 1 Year 2 Year 3

0

15

30

45

60

75

90

105

120

135

150

Per

cent

of

Bas

elin

e In

sulin

Follow-Up

Primary Outcomes Post First InfusionUp to Re-Infusion, Complete Islet Failure, or Last Follow-UpAccording to Pre-Infusion Recipient, Donor, Procurement,

and Islet Characteristics

Islet Alone Recipients

Primary Outcomes Post First InfusionUp to Re-Infusion, Complete Islet Failure, or Last Follow-UpAccording to Pre-Infusion Recipient, Donor, Procurement, and Islet Characteristics Islet Alone Recipients (continued)

Primary Outcomes Post First InfusionUp to Re-Infusion, Complete Islet Failure, or Last Follow-UpAccording to Pre-Infusion Recipient, Donor, Procurement, and Islet Characteristics Islet Alone Recipients (continued)

Primary Outcomes Post First InfusionUp to Re-Infusion, Complete Islet Failure, or Last Follow-UpAccording to Pre-Infusion Recipient, Donor, Procurement, and Islet Characteristics Islet Alone Recipients (continued)

Primary Outcomes Post First InfusionUp to Re-Infusion, Complete Islet Failure, or Last Follow-UpAccording to Pre-Infusion Recipient, Donor, Procurement, and Islet Characteristics Islet Alone Recipients (continued)

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

Significant < 0.10

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

Univariately Significant < 0.10

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

Significant < 0.10

Reinfusion Post First Infusion Forest Plot (Hazard Ratio ± 95% Confidence Interval) Of Factors Univariately Significant < 0.10

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor,

Procurement, and Islet Characteristics

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor,

Procurement, and Islet Characteristics (continued)

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor,

Procurement, and Islet Characteristics (continued)

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor,

Procurement, and Islet Characteristics (continued)

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor,

Procurement, and Islet Characteristics (continued)

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor,

Procurement, and Islet Characteristics (continued)

Primary Outcomes Post Last InfusionAccording to Pre-Infusion Recipient, Donor,

Procurement, and Islet Characteristics (continued)

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

Factors Univariately Significant p < 0.10

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

Univariately Significant p < 0.10

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

Significant p < 0.10

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

256 183 58 220 187 116 73

(Five at pre-inf 1)Values greater than 400 mg/dL are not displayed

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

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

41 32 7 33 30 23 16

(Two at pre-inf 1)

Values greater than 400 mg/dL are not displayed

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

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

HbA1C (%)

Pre Infusion and Post Last Infusion

A. Islet Alone Recipients B. Islet After Kidney Recipients

258 167 57 210 179 115 73

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

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

42 29 8 30 27 21 14

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

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

258 167 52 210 203 144 110

(One at pre-inf 2, three at month 6 and one at year 1)

Values greater than 6 ng/ml are not displayed

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

0

1

2

3

4

5

6

ng/m

L

Follow-Up

39 29 5 30 27 24 17

(One at year 2)Values greater than 6 ng/ml are not displayed

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

0

1

2

3

4

5

6

ng/m

L

Follow-Up

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

Islet Alone Recipients with One Infusion

76 53 42 22 16

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

HbA1C (%)

Pre-Infusion and Post Last Infusion Islet Alone Recipients with One Infusion

73 51 39 23 16

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

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

Islet Alone Recipients with One Infusion

74 51 50 37 31

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

1

2

3

4

5

6

ng/m

L

Follow-Up

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

Islet Alone Recipients with Two Infusions

122 124 113 99 65 41

(Two at pre-inf 1)Values greater than 400 mg/dL are not displayed

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

0

50

100

150

200

250

300

350

400

mg/d

L

Follow-Up

HbA1C (%)

Pre Infusion and Post Last InfusionIslet Alone Recipients with Two Infusions

126 115 107 96 64 41

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

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

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

Islet Alone Recipients with Two Infusions

126 113 107 104 78 56

(One at pre-inf 2, three at month 6 and one at year 1)

Values greater than 6 ng/mL are not displayed

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

0

1

2

3

4

5

6

ng/m

L

Follow-Up

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

Islet Alone Recipients with Three Infusions

54 55 55 51 45 29 16

(Three at pre-inf 1)

Values greater than 400 mg/dL are not displayed

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

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

HbA1C (%)

Pre Infusion and Post Last InfusionIslet Alone Recipients with Three Infusions

55 48 53 49 43 28 16

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

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

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

Islet Alone Recipients with Three Infusions

54 50 49 48 46 28 22

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

0

1

2

3

4

5

6

ng/m

L

Follow-Up

Fasting Plasma Glucose (mg/dL) Post Last InfusionRecipients Who Ever Achieved Insulin Independence

A. Islet Alone Recipients B. Islet After Kidney Recipients

172 158 147 100 66

(Four at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

28 23 21 17 12

(One at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

Fasting Plasma Glucose (mg/dL) Post Last InfusionRecipients Who Never Achieved Insulin Independence

A. Islet Alone Recipients B. Islet After Kidney Recipients

84 62 40 16 7

(One at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

13 10 9 6 4

(One at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

400

mg/

dL

Follow-Up

HbA1C (%) Post Last Infusion

Recipients Who Ever Achieved Insulin Independence

A. Islet Alone Recipients B. Islet After Kidney Recipients

172 150 142 99 66

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

27 22 19 16 12

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

HbA1C (%) Post Last Infusion

Recipients Who Never Achieved Insulin Independence

A. Islet Alone Recipients B. Islet After Kidney Recipients

86 60 37 16 7

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

15 8 8 5 2

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

Basal Plasma C-Peptide (ng/mL) Post Last InfusionRecipients Who Ever Achieved Insulin Independence

A. Islet Alone Recipients B. Islet After Kidney Recipients

175 150 147 96 76

(Two at month 6)Values greater than 6 ng/mL are not displayed

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

1

2

3

4

5

6

ng/m

L

Follow-Up

28 22 19 17 12

(One at year 2)Values greater than 6 ng/mL are not displayed

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

1

2

3

4

5

6

ng/m

L

Follow-Up

Basal Plasma C-Peptide (ng/mL) Post Last InfusionRecipients Who Never Achieved Insulin Independence

A. Islet Alone Recipients B. Islet After Kidney Recipients

83 60 56 48 34

(One at month 6 and one at year 1)Values greater than 6 ng/mL are not displayed

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

1

2

3

4

5

6

ng/m

L

Follow-Up

11 8 8 7 5

Pre Inf 1 Month 6 Year 1 Year 2 Year 3

0

1

2

3

4

5

6

ng/m

L

Follow-Up

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

Insulin Independent Recipients

A. Islet Alone Recipients B. Islet After Kidney Recipients

256 14 30 122 120

(Five at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

100

200

300

400

mg/

dL

Follow-Up

41 2 5 16 9

(Two at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

100

200

300

400

mg/

dL

Follow-Up

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

Insulin Dependent Recipients

A. Islet Alone Recipients B. Islet After Kidney Recipients

256 242 232 113 85

(Five at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

100

200

300

400

mg/

dL

Follow-Up

41 34 32 22 18

(Two at pre-inf 1)Values greater than 400 mg/dl are not displayed

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

100

200

300

400

mg/

dL

Follow-Up

HbA1C (%)

Pre and Post First InfusionInsulin Independent Recipients

A. Islet Alone Recipients B. Islet After Kidney Recipients

258 24 116 114

Pre Inf 1 Day 30 Month 6 Year 1

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

42 3 15 9

Pre Inf 1 Day 30 Month 6 Year 1

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

HbA1C (%)

Pre and Post First InfusionInsulin Dependent Recipients

A. Islet Alone Recipients B. Islet After Kidney Recipients

258 139 105 79

Pre Inf 1 Day 30 Month 6 Year 1

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

42 15 17 16

Pre Inf 1 Day 30 Month 6 Year 1

2.5

5.0

7.5

10.0

12.5

%

Follow-Up

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

Insulin Independent Recipients

A. Islet Alone Recipients B. Islet After Kidney Recipients

258 10 28 120 119

(Two at month 6)Values greater than 6 ng/mL are not displayed

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

1

2

3

4

5

6

ng/m

L

Follow-Up

39 1 4 16 9

(One at year 2)Values greater than 6 ng/mL are not displayed

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

258 219 222 106 95

(One at month 6 and one at year 1)Values greater than 6 ng/mL are not displayed

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

1

2

3

4

5

6

ng/m

L

Follow-Up

39 30 32 19 18

Pre Inf 1 Day 7 Day 30 Month 6 Year 1

0

1

2

3

4

5

6

ng/m

L

Follow-Up

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

A. Islet Alone Recipients

Insulin Status Independent Dependent

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Infusion 1N=0 :256

Month 6N=136 :83

Year 1N=109 :78

Year 2N=58 :58

Year 3N=29 :44

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

B. Islet After Kidney Recipients

Insulin Status Independent Dependent

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Infusion 1N=0 :41

Month 6N=17 :16

Year 1N=12 :18

Year 2N=7 :16

Year 3N=2 :14

Insulin Dependent Recipients with Basal C-Peptide 0.5 ng/mL

Post Last InfusionA. Islet Alone Recipients

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=258

Month 6N=80

Year 1N=96

Year 2N=97

Year 3N=83

Insulin Dependent Recipients with Basal C-Peptide 0.5 ng/mL

Post Last InfusionB. Islet After Kidney Recipients

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=39

Month 6N=14

Year 1N=17

Year 2N=18

Year 3N=15

Recipients with HbA1C < 6.5%

Post Last Infusion by Insulin StatusA. Islet Alone Recipients

Insulin Status Independent Dependent

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Infusion 1N=0 :258

Month 6N=131 :78

Year 1N=108 :71

Year 2N=57 :58

Year 3N=30 :43

Recipients with HbA1C < 6.5%

Post Last Infusion by Insulin StatusB. Islet After Kidney Recipients

Insulin Status Independent Dependent

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Infusion 1N=0 :42

Month 6N=16 :14

Year 1N=11 :16

Year 2N=6 :15

Year 3N=2 :12

Pre-Infusion Recipient Lab Summary by Infusion SequenceIslet Alone Recipients

Pre-Infusion Recipient Lab Summary by Infusion SequenceIslet After Kidney Recipients

Metabolic Summary by Follow-Up Post Last InfusionIslet Alone Recipients

Metabolic Summary by Follow-Up Post Last InfusionIslet After Kidney Recipients

Metabolic Summary Post Last Infusion by Insulin StatusIslet Alone Recipients

Metabolic Summary Post Last Infusion by Insulin StatusIslet Alone Recipients (continued)

Secondary Complications of DiabetesPre First Infusion and Post Last Infusion

All Allograft Recipients

Secondary Complications of DiabetesPre First Infusion and Post Last Infusion

All Allograft Recipients (continued)

Secondary Complications of DiabetesPre First Infusion and Post Last Infusion

All Allograft Recipients (continued)

Secondary Complications of DiabetesPre First Infusion and Post Last Infusion

All Allograft Recipients (continued)

Ocular ComplicationsPre First Infusion and Post last Infusion

All Allograft Recipients

Ocular ComplicationsPre First Infusion and Post last Infusion

All Allograft Recipients (continued)

Chapter 6: Liver, Kidney, Lipid and PRA Effects

Incidence of Abnormal Liver Function Testsat Any Scheduled Time Post First Infusion

All Allograft Recipients

and at Month 6, Year 1, Year 2, and Year 3 after the last infusion procedure occurs.Lab values analyzed in this Exhibit are taken prior to each subsequent infusion

>=3X ULN2-3X ULN1-2X ULN

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

ALT AST Alkaline Phosphatase Total Bilirubin

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

269 183 61 212 173 107 68

(One at pre-inf 2)Values greater than 150 IU/L are not displayed

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

25

50

75

100

125

150

IU/L

Follow-Up

43 33 6 33 29 22 14

(One at pre-inf 2)Values greater than 150 IU/L are not displayed

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

25

50

75

100

125

150

IU/L

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

269 183 61 212 173 107 68

(One at pre-inf 2)Values greater than 120 IU/L are removed for display

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

20

40

60

80

100

120

IU/L

Follow-Up

43 33 6 33 29 22 14

(One at pre-inf 2)Values greater than 150 IU/L are not displayed

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

20

40

60

80

100

120

IU/L

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

264 179 59 207 176 107 69

(Two at pre-inf 2, one at month 6, and one at year 1)Values greater than 350 IU/L are removed for display

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

IU/L

Follow-Up

41 33 6 32 29 22 14

(Three at pre-inf 1, four at pre-inf 2, two at year 1, and one at year 2)Values greater than 350 IU/L are removed for display

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

IU/L

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

265 182 59 206 174 106 66

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

mg/

dL

Follow-Up

42 33 7 30 29 22 13

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

mg/

dL

Follow-Up

Incidence of Abnormal Lipid Testsat Any Scheduled Time Post First Infusion

All Allograft Recipients

and at Month 6, Year 1, Year 2, and Year 3 after the last infusion procedure occurs.Lab values analyzed in this Exhibit are taken prior to each subsequent infusion

2-3X ULN1-2X ULN

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

Total Cholesterol Triglycerides

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

263 158 55 197 179 111 70

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

mg/

dL

Follow-Up

41 25 5 29 26 22 15

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

mg/

dL

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

260 146 46 185 169 100 66

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

25

50

75

100

125

150

mg/

dL

Follow-Up

36 15 2 18 19 15 12

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

25

50

75

100

125

150

mg/

dL

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

260 146 45 184 168 101 66

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

mg/

dL

Follow-Up

36 15 2 18 19 15 12

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

mg/

dL

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

263 157 55 197 178 109 70

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

400

450

mg/

dL

Follow-Up

41 25 5 29 26 22 15

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

300

350

400

450

mg/

dL

Follow-Up

Incidence of Increase in Serum Creatinine (mg/dL) Greater than 0.5 from Baseline

at Any Scheduled Time Post First InfusionAll Allograft Recipients

and at Month 6, Year 1, Year 2, and Year 3 after the last infusion procedure occurs.Lab values analyzed in this Exhibit are taken prior to each subsequent infusion

>1.0 mg/dL increase from baseline0.5 - 1.0 mg/dL increase from baseline

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

Islet Alone Islet After Kidney

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

271 186 61 219 190 121 75

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

mg/

dL

Follow-Up

44 32 8 32 30 22 16

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

mg/

dL

Follow-Up

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

A. Islet Alone Recipients B. Islet After Kidney Recipients

222 96 26 119 118 44 22

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

mL/

min

/1.7

3m2

Follow-Up

28 8 1 12 14 9 7

PreInf 1

PreInf 2

PreInf 3

Month 6 Year 1 Year 2 Year 3

0

50

100

150

200

250

mL/

min

/1.7

3m2

Follow-Up

GFR (mL/min/1.73m2)Pre Infusion and Post Last Infusion

A. Islet Alone Recipients B. Islet After Kidney Recipients

271 186 61 219 190 121 75

Values greater than 180 ml/min/1.73 m2 have been removed for display

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

0

30

60

90

120

150

180

ml/m

in/1

.73

m2

Follow-Up

44 32 8 32 30 22 16

Values greater than 180 ml/min/1.73 m2 have been removed for display

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

0

30

60

90

120

150

180

ml/m

in/1

.73

m2

Follow-Up

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

Islet Alone Recipients

247 165 55 140 123 78 48

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

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

Islet Alone Recipients

154 52 135 117 75 42

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

-25

0

25

50

75

100C

hang

e fr

om P

re I

nfus

ion

1

Follow-Up

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

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

130 115 64 41

Month 6 Year 1 Year 2 Year 3

0

10

20

30

40

50

60

70

80

90

100%

Follow-Up

Class I PRA Post Last InfusionNon-Immunosupressed Islet Alone Recipients

Class I PRA Post Last InfusionImmunosupressed Islet Alone Recipients

Chapter 7: Adverse Events

Percent of Recipients with an Adverse Event (AE) or Serious Adverse Event (SAE)

in Year 1 Post First Infusion

Islet Alone (N=279) Islet After Kidney (N=46)

Recipients with an AE

Recipients with an SAE

Recipients with an AE

Recipients with an SAE

N % N % N % N %

Any Event

179 64% 127 46% 24 52% 20 43%

Related to either the infusion procedure or immunosuppression therapy

147 53% 95 34% 19 41% 15 33%

Related to the infusion procedure

93 33% 66 24% 12 26% 9 20%

Related to immunosuppression therapy

97 35% 47 17% 9 20% 8 17%

Total Number of Adverse Events and Serious Adverse Events

in Year 1 Post First Infusion

Islet Alone Islet After Kidney

Adverse Events

Serious Adverse Events Adverse Events

Serious Adverse Events

N % N % N % N %

Total

509 100.0 252 100.0 44 100.0 34 100.0

Related to the infusion procedure

146 28.7 95 37.7 16 36.4 10 29.4

Related to immunosuppression therapy

155 30.5 63 25.0 16 36.4 14 41.2

Related to both the infusion procedure and immunosuppression therapy

23 4.5 8 3.2 - 0.0 - 0.0

Related to neither the infusion procedure nor immunosuppression therapy

185 36.3 86 34.1 12 27.3 10 29.4

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

All Allograft Recipients

Any SAESAE related to either the infusion procedure or immunosupressionSAE related to the infusion procedureSAE related to immunosupression

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

Year of First Infusion1999N=6

2000N=12

2001N=35

2002N=69

2003N=41

2004N=47

2005N=60

2006N=36

Serious Adverse Event Type 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

Islet Alone Recipients

Most Common Serious Adverse Events MedDRA Preferred Term

Islet After Kidney Recipients

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

Summary of Reported Neoplasms

Summary of Reported Neoplasms (continued)

Listing of Reported Hemorrhages and Portal Vein Thromboses

All Allograft Recipients

Listing of Reported Hemorrhages and Portal Vein Thromboses

All Allograft Recipients (continued)

Listing of Reported Hemorrhages and Portal Vein Thromboses

All Allograft Recipients (continued)

Listing of Reported Hemorrhages and Portal Vein Thromboses

All Allograft Recipients (continued)

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

by Infusion SequenceIslet Alone Recipients

271 184 58

1 2 3

0

5

10

15

20

Num

ber

of D

ays

Infusion Sequence

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

by Infusion SequenceIslet After Kidney Recipients

43 33 8

1 2 3

0

10

20

30

40

50

Num

ber

of D

ays

Infusion Sequence

Hospitalization Experienced Post Last Infusion by Total Number of Infusions Received

Islet Alone Recipients

Hospitalization Experienced Post Last Infusion by Total Number of Infusions Received

Islet After Kidney Recipients

Chapter 8: Registry Data Quality Review

Expected and Submitted Forms by Infusion SequenceA) Islet Alone Recipients

Expected and Submitted Forms by Infusion SequenceB) Islet After Kidney Recipients

Expected and Submitted Follow-Up Forms Post Last infusion

All Allograft Recipients

Extent of Follow-Up Post Last InfusionAll Allograft Recipients

CITR Coordinating Center(July 2007 – July 2008)

PI: Franca Benedicty Barton

Co-PI: Donald Stablein

Yamini Damodharan

Ruth Danoff

Jodi DeStefano

Andrew Heitman

Krista Huang

Christina Mandzuk

Steve Wease

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

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