Embed Size (px)
Citation preview
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
