The Swiss Transplant Cohort Study
1.5.2008 – 30.6.2013
PD Dr Michael T Koller
National Epidemiologist &
Head of the data center of the STCS
On behalf of all members of the STCS
michael.koller@usb.ch
www.stcs.ch
We write the
medical history that
others read.4)
4)
Not long ago, the University
Hospital of Zurich
transplanted to two patients
simultanously a double lung
by segmentation of the donor
lung . The girl and the jung
men, who suffered from birth
of CF got a new life – and
medicine a new chapter of
history.
An example of STCS collaboration
• E-Mail the ad to … stcs@usz.ch
• What was exactly done in Zürich?
• How was the outcome in the recipients?
• Response time from Zürich: 45’ !!
USZ: segmentation of the donor lung …
R1: 19 y young male
(80001753). Double lung.
15.12.2010
Donor: 33y old male
† ICH
16.12.2010
R2: 14 y young female
(80001757). Double lung.
Recipient 80001757 & 80001753:
longitudinal follow-up
Recipient 80001757 & 80001753:
The STCS psychosocial questionaire: «Patient, how is your life?»
The 14 years old female
No PSQ: child.
Visit
The 19 years old man
BL
PSQ 0: not available
FUP 6
PSQ 1: student, never misses a dose of IS; sleep
quality of 10/10!; No smoking;
No problems to perform usual activities;
No pain or discomfort.
Most of the time cheerful; Single;
FUP 12
PSQ 2: no change
FUP 24
PSQ 3 (V2): phys activity 2/week 60 min, easy;
QoL: 86/100 VAS. Team trust: 10/10.
Full adherent to medication.
FUP 36
PSQ 4(V2): phys activity 3/week 45 min, very
hard!! QoL: 91/100 VAS; Team trust: 10/10. No
smoking. Full adherent to drugs. Still single.
«The destiny of individual patients»
«The destiny of
all solid organ recipients in
Switzerland»
Example 1
Lung transplantation (LTX) surivival
STCS post-LTX overall patient survival
Freeman Hospital,
Newcastle , adult CF only,
1994 - 2004
12%
US: Columbia University
Medical Center (CUMC),
2001-2008, n=274
25%
40%
ISHLT Registry (worlwide,
US, Europe). 2004-2010,
n=17’715
UNOS Data from 15`642
adult lung TPX recipients
between 1987 and 2009
and in US 61 centers
Post-LTX overall patient survival: STCS vs ISHLT
100
2004-6/2010 (N=17,715)
N at risk = 1,055
Survival (%)
80
60
40
20
0
0
1
2
3 Years 4
5
6
7
8
9
1
Lessons from international benchmarking
• Compared to the others: we perform well!
• But: 40% of all LTX recipients are dead by 5 years
Example 2
Heart transplantation (HTX) survival
Post-HTX overall patient survival
18%
22%
25%
UNOS Data, 8029 HTX
recipients between
2001 and 2009 and in US 61
centers
CTS Registry (Europe).
1985-2011, n=28’828
Only first TPX
ISHLT Registry (worlwide,
US, Europe). 1982-2011,
n=103’299
Post-HTX center-specific survival:
The early STCS experience: 1.5.2008 – 31.12.2011
Post-HTX Center-specific survival:
The updated STCS experience: 1.5.2008 – 30.06.2013
Lessons from national HTX benchmarking
Center-specific differences in post-HTX survival
disappeared with time…
1. The increase of the sample size (n=85  n=169)
reduced differences due to random variation
2. The discussion of center-specific data lead to critical
review of case fatalities with impact on patient care
Example 3
Renal transplantation (RTX)
by type of donor
Post-RTX patient survival by donor-type
Post-RTX patient survival by donor-type
AB0 compatible / AB0 incompatible
Post-RTX incidence of graft-failure by donor-type
AB0 compatible / AB0 incompatible
4 «simultaneous» failures of AB0 incompatible
allografts  failure rate stable at ~ 5%
-
ACR vascular + TMA
ACR vascular + ATN
ACR vascular + «ARF»
AHR
Center
AB0 not c
USZ
26
USB
38
CHUV
0
BE
8
HUG
16
SG
3
Total
91
RTX recipients from living vs deceased donation
RTX recipients
deceased donation
769
56.1
(44.8, 63.7)
37 (4.8%)
491 (63.8%)
RTX recipients
living donation
552
50.5
(37.2, 60.2)
22 (4%)
367 (66.5%)
Donor age (in yrs), median
- IQR
55
(41, 63)
53
(45, 61)
HLA A compatible*, n (%)
HLA B compatible*, n (%)
HLA DR compatible*, n (%)
Class I DSA pos
Class II DSA pos
DGF, n (%)
PNF, n (%)
107 (14.1%)
42 (5.5%)
98 (12.9%)
109 (44.1%)
86 (41%)
122 (15.9%)
8 (1.4%)
78 (14.3%)
55 (10.1%)
79 (14.5%)
53 (35.1%)
47 (36.2%)
8 (1%)
0 (0%)
Current smoker, n (%)
Higher education, n (%)
No work capacity (0%), n (%)
110 (14.3%)
119 (15.5%)
318 (41.4%)
59 (10.7%)
169 (30.6%)
184 (33.3%)
Number of patients
Recipient age (in yrs), median
- IQR
Pediatric, n (%)
Male gender, n (%)
* Number of mismatches = 0
Baseline characteristics
Donor-type by center in RTX
Example 4
Is there anything similar between lung and liver
transplantation?
Failure-free survival in liver vs lung tpx recipients
Exactly the same first-year survival !
Example 5
Is there anything similar between …
heart and kidney-pancreas
transplantation?
Failure-free survival in HTX vs Kidney-Pancreas
recipients
Incidence of graft-failure by organ
Graft-failure in double TPX
Kidney
Liver
Pancreas
Total
Kidney - Liver
1
1
0
2
Kidney – Pancreas
(n=57)
0
0
10
10
Pancreas - Small bowel
0
0
1
1
Total
1
1
11
13
STCS project status
http://www.stcs.ch/publications/stcs-reports/
Patient recruitment by organ
Total
Re- Secon
TPX d TPX
(%)
(%)
Kidney 1321 15.3
1.9
Liver
Lung
Heart
Kidney Pancreas
481
234
169
57
3.7
3.0
0.6
0.0
1.5
1.3
0.0
7.0
….
…
…
…
Number of patients
Patients
(%)
Total number
Pediatric patients
2358
123
100.0
5.4
Single Tpx at enrolment
Double Tpx at enrolment
Triple Tpx at enrolment
2241
114
3
95.0
4.8
0.1
1st Tpx at enrolment
Re-Tpx at enrolment
2nd Tpx at enrolment
2057
237
64
87.2
10.1
2.7
Patients follow-up
Median follow-up duration (years)
IQR (years)
Patient with longest follow-up (years)
Number of deaths
Patients with (at least one) graft failure
Patients lost to follow-up*
Follow-up
2.7
1.4 - 4.08
5.6
261
154
14
Current informed consent by center
Achievements and challenges
Achievements
Scientific committee: completed / published projects
1: Bucheli E, Kralidis G, Boggian K, Cusini A, Garzoni C, Manuel O, Meylan PR, Mueller NJ, Khanna N, van Delden C, Berger C,
Koller MT, Weisser M; The Swiss Transplant Cohort Study. Impact of enterococcal colonization and infection in solid organ
transplantation recipients from the Swiss Transplant Cohort Study.
Transpl Infect Dis. 2013 Dec 16.
2: De Geest S, Burkhalter H, Berben L, Bogert LJ, Denhaerynck K, Glass TR, Goetzmann L, Kirsch M, Kiss A, Koller MT, PiotZiegler C, Schmidt-Trucksäss A; Psychosocial Interest Group, Swiss Transplant Cohort Study. The Swiss Transplant Cohort
Study's framework for assessing lifelong psychosocial factors in solid-organ transplants. Prog Transplant. 2013 Sep;23(3):23546.
3: Burkhalter H, Wirz-Justice A, Cajochen C, Weaver T, Steiger J, Fehr T, Venzin RM, De Geest S. Validation of a single item to
assess daytime sleepiness for the Swiss Transplant Cohort Study. Prog Transplant. 2013 Sep;23(3):220-8.
4: Manuel O, Kralidis G, Mueller NJ, Hirsch HH, Garzoni C, van Delden C, Berger C, Boggian K, Cusini A, Koller MT, Weisser M,
Pascual M, Meylan PR; Swiss Transplant Cohort Study. Impact of antiviral preventive strategies on the incidence and outcomes
of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2013 Sep;13(9):2402-10.
5: Koller MT, van Delden C, Müller NJ, Baumann P, Lovis C, Marti HP, Fehr T,Binet I, De Geest S, Bucher HC, Meylan P, Pascual M,
Steiger J. Design and methodology of the Swiss Transplant Cohort Study (STCS): a comprehensive prospective nationwide
long-term follow-up cohort. Eur J Epidemiol. 2013
Apr;28(4):347-55.
6: Berger C, Boggian K, Cusini A, van Delden C, Garzoni C, Hirsch HH, Khanna N,Koller M, Manuel O, Meylan P, Nadal D, Weisser
M, Mueller NJ; Transplant Infectious Diseases Working Group, Swiss Transplant Cohort Study. Relevance of cohort studies for
the study of transplant infectious diseases. Curr Opin Organ
Transplant. 2012 Dec;17(6):581-5.
Evolution of scientific projects
applications
20
18
16
14
12
approved
10
expected
8
6
4
2
0
2009
2010
2011
2012
2013
2014
2015
International collaborations
Collaboration / Partner
Topic
A. Humar, Edmonton (Toronto)
CMV pathogenesis
Giral/Foucher, DIVAT cohort, France
Long-term evolution after kidney transplantation
German Center for Infection
Research, Munich, Germany
Sharing of infrastructural experience
Comprehensive ID outcome collection
SysClad (EU project), France
Systems prediction of Chronic Lung Allograft
Dysfunction
J Wilson‐McManus, PROOF, Canada
Biomarkers in Transplantation
Aguado, Resitra cohort, Spain
European analysis of rare Infectious Diseases
endpoints (Aspergillosis)
Achievements
• Recent SNSF Re-funding … the 3rd period!
• Active working groups: LDM, PSIG, ID, Genetic,
Lab
• Comprehensive reporting on TPX outcomes
• Operating data center providing project support
and data upates
Challenges
• IT IS INCREASING!
Patients, Transplantations, Organs, Follow-up,
Events, Samples, Projects, Disk volume, Staff,
Meetings, Data requests, official/political
requests …
• Increase the scientific output
• Perform sophisticated national and international
center benchmarking
• Don’t stop to let that system grow!
Challenges … our patients
Board of Representatives
• 1 per center (6, with one vote each)
• Representation Ticino (1) to be discussed
• Stem cell (1)
• Pediatrics (1)
• Swisstransplant (1)
• Executive office (3, 1 vote)
• IT and Epidemiology (no vote)
Executive Office
(MP, CVD + JS)
Working groups
Coordination
Data center
• Lab group (PM)
• Psycho social group (SDG)
• ID group (CVD)
• Local data managers group (EB)
• Pediatric group (DN)
• Stem cell group (JP)
Head: MK
Central
Data
Management
(JR,MW)
Epidemiology (MK)
BioStatistician
(SS)
IT
Head: CL
(PB)
Scientific Committee
Heart
3
ID
2
Lung
2
Immunology
2
Liver
(incl. small
bowel)
3
Psychosocial group
2
IT
1
Kidney
6
Epidemiology
incl. data management center
1
Pancreas
islet
2
Stem cell
Alogeneiic 3
Swisstransplant
1
Executive office
3
(1 vote)
Pediatrics
1
Thank you!
Survival of STCS liver recipients
Achievements
Scientific committee: 39 running projects
Recipients 80001757 & 80001753
The 14 years old female
Donor: 33 y, male, † ICH
TPX: 16.12.2010, double lung!
2 RT infections:
- Mycobacterium other than
tuberculosis (MOTT)
- Aspergillus fumigatus
Complications: Pleural effusion
No PSQ: child.
Visit
BL
FUP
The 19 years old man
Donor: 33 y, male, † ICH
TPX: 15.12.2010, double lung!
No infections! No complications!
PSQ 1: student, never misses a dose of IS,
sleep quality of 10/10!; No smoking; No
problems to perform usual activities; Most
of the time cheerful; Single;
PSQ 3 (V2!): phys activity 2/week 60 min,
easy; QoL: 86/100 VAS. Team trust: 10/10.
Full adherent to drugs.
PSQ 4: phys activity 3/week 45 min, very
hard!! QoL: 91/100 VAS; Team trust: 10/10.
No smoking. Full adherent to drugs. Still
single.