The Swiss Transplant Cohort Study1.5.2008 – 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 STCSmichael.koller@usb.ch

www.stcs.ch

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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.

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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 …

Donor: 33y old male† ICH

R1: 19 y young male (80001753). Double lung.

R2: 14 y young female(80001757). Double lung.

16.12.2010

15.12.2010

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Recipient 80001757 & 80001753: longitudinal follow-up

ID: M

OTTID: A

spergillus

Pleural effusion

No events

Recipient 80001757 & 80001753:The STCS psychosocial questionaire: «Patient, how is your life?» The 14 years old female Visit The 19 years old man

No PSQ: child. BL

FUP 6

FUP 12

FUP 24

FUP 36

PSQ 0: not available

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;

PSQ 2: no change

PSQ 3 (V2): phys activity 2/week 60 min, easy; QoL: 86/100 VAS. Team trust: 10/10. Full adherent to medication.

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.

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«The destiny of individual patients»

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«The destiny of all solid organ recipients in

Switzerland»

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Example 1

Lung transplantation (LTX) surivival

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STCS post-LTX overall patient survival

Freeman Hospital, Newcastle , adult CF only,

1994 - 2004

US: Columbia University Medical Center (CUMC),

2001-2008, n=274

UNOS Data from 15`642 adult lung TPX recipients between 1987 and 2009

and in US 61 centers

ISHLT Registry (worlwide, US, Europe). 2004-2010,

n=17’715

40%

12%

25%

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0 1 2 3 4 5 6 7 8 9 10 11 12 13 140

20

40

60

80

100

2004-6/2010 (N=17,715)

Years

Surv

ival

(%)

N at risk = 1,055

Post-LTX overall patient survival: STCS vs ISHLT

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Lessons from international benchmarking

• Compared to the others: we perform well!

• But: 40% of all LTX recipients are dead by 5 years

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Example 2

Heart transplantation (HTX) survival

Post-HTX overall patient survival

CTS Registry (Europe). 1985-2011, n=28’828

Only first TPX

ISHLT Registry (worlwide, US, Europe). 1982-2011,

n=103’299

UNOS Data, 8029 HTX recipients between

2001 and 2009 and in US 61 centers

25%22%

18%

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Post-HTX center-specific survival:The early STCS experience: 1.5.2008 – 31.12.2011

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Post-HTX Center-specific survival:The updated STCS experience: 1.5.2008 – 30.06.2013

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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

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Example 3

Renal transplantation (RTX) by type of donor

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Post-RTX patient survival by donor-type

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Post-RTX patient survival by donor-typeAB0 compatible / AB0 incompatible

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Post-RTX incidence of graft-failure by donor-typeAB0 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 donationBaseline characteristics

RTX recipientsdeceased donation

RTX recipientsliving donation

Number of patients 769 552Recipient age (in yrs), median 56.1 50.5 - IQR (44.8, 63.7) (37.2, 60.2)Pediatric, n (%) 37 (4.8%) 22 (4%)Male gender, n (%) 491 (63.8%) 367 (66.5%)

Donor age (in yrs), median 55 53 - IQR (41, 63) (45, 61)

HLA A compatible*, n (%) 107 (14.1%) 78 (14.3%)HLA B compatible*, n (%) 42 (5.5%) 55 (10.1%)HLA DR compatible*, n (%) 98 (12.9%) 79 (14.5%)Class I DSA pos 109 (44.1%) 53 (35.1%)Class II DSA pos 86 (41%) 47 (36.2%)DGF, n (%) 122 (15.9%) 8 (1%)PNF, n (%) 8 (1.4%) 0 (0%)

Current smoker, n (%) 110 (14.3%) 59 (10.7%)Higher education, n (%) 119 (15.5%) 169 (30.6%)No work capacity (0%), n (%) 318 (41.4%) 184 (33.3%)

* N

umbe

r of m

ism

atch

es =

0

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Donor-type by center in RTX

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Example 4

Is there anything similar between lung and liver transplantation?

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Failure-free survival in liver vs lung tpx recipients

Exactly the same first-year survival !

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Example 5

Is there anything similar between … heart and kidney-pancreas

transplantation?

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Failure-free survival in HTX vs Kidney-Pancreas recipients

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Incidence of graft-failure by organ

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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

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STCS project status

http://www.stcs.ch/publications/stcs-reports/

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Patient recruitment by organTotal Re-

TPX(%)

Second TPX

(%)

Kidney 1321 15.3 1.9

Liver 481 3.7 1.5Lung 234 3.0 1.3

Heart 169 0.6 0.0Kidney -

Pancreas57 0.0 7.0

…. … … …

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Number of patients

Patients (%)

Total number 2358 100.0Pediatric patients 123 5.4

Single Tpx at enrolment 2241 95.0Double Tpx at enrolment 114 4.8

Triple Tpx at enrolment 3 0.1

1st Tpx at enrolment 2057 87.2Re-Tpx at enrolment 237 10.1

2nd Tpx at enrolment 64 2.7

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Patients follow-up

Follow-upMedian follow-up duration (years) 2.7

IQR (years) 1.4 - 4.08Patient with longest follow-up (years) 5.6

Number of deaths 261Patients with (at least one) graft failure 154

Patients lost to follow-up* 14

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Current informed consent by center

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Achievements and challenges

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AchievementsScientific 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, Piot-Ziegler 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):235-46.

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. 2013Apr;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 OrganTransplant. 2012 Dec;17(6):581-5.

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Evolution of scientific projects applications

2009 2010 2011 2012 2013 2014 20150

2

4

6

8

10

12

14

16

18

20

approvedexpected

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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 experienceComprehensive 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)

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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

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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!

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Challenges … our patients

Heart3

Liver(incl. small

bowel)3

Kidney6

Pancreasislet

2

Stem cellAlogeneiic 3

ID2

Lung2

Scientific Committee

Data center

Executive Office(MP, CVD + JS)

Coordination

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)

Pediatrics1

Swisstransplant1

Immunology2

IT1

Epidemiologyincl. data management center

1

Executive office3

(1 vote)

Psychosocial group2

Working groups• 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 Mana-gement (JR,MW)

Epidemio-logy (MK)

Bio-Statistician (SS)

IT

Head: CL

(PB)

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Thank you!

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Survival of STCS liver recipients

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46

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AchievementsScientific committee: 39 running projects

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Recipients 80001757 & 80001753 The 14 years old female Visit The 19 years old man

Donor: 33 y, male, † ICHTPX: 16.12.2010, double lung!

BL Donor: 33 y, male, † ICHTPX: 15.12.2010, double lung!

2 RT infections: - Mycobacterium other than tuberculosis (MOTT)- Aspergillus fumigatus

Complications: Pleural effusion

No PSQ: child.

FUP 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.

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