10 years prospective donor follow-up in switzerland · hilfslinien anzeigen über menu: donor...

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10 years Prospective Donor

Follow-Up in Switzerland

Swisstransfusion

24.08.2018


Donor Follow-Up in Switzerland (1)

Swisstransfusion, 24.08.2018 | 2

• On July 1st, 2007 the Swiss law on transplantation was enacted. SBSC

(then still Swiss Foundation Blood Stem Cells) was mandated by the

Federal Office of Health

- to run a registry for unrelated blood stem cell donors in CH

- to provide lifelong follow-up for all donors of haematopoietic stem

cells (HSC) - related and unrelated donors – having donated in CH

• Donor follow-up (FU) data for unrelated blood stem cell donors (URD) had

been consistently collected in Switzerland since the foundation of the

„Swiss Bone Marrow Donor Registry“ in 1988

• Follow-up was also performed for some related donors (RD) by the

collection centres, but not systematically and each centre had their own

procedure. RD FUP is generally lacking worldwide




standardisation and harmonisation of the FUP

procedures for RD and URD

by SBSC with „Swiss Blood Stem Cell Transplantation“ (SBST,

Swiss scientific board for HSCT)

• SBSC works closely with the EBMT donor outcome committee,

standardisation of FU is a general aim worldwide

• Since 01.07.2007 FUP data on every HSC donation performed by

RD and URD in Switzerland are collected prospectively in the

EBMT database ProMise. (Same database as for patient FUP-data)

• Donors sign an informed consent for FU and data collection in the

EBMT database

• 10 year study period from 01.07.2007 until 30.06.2017



Donor Follow-Up in Switzerland (3): 2 periods

Period 1: from July 1st, 2007 until August 30th, 2013

• Time-points of data collection: time of harvest, 1month, 6 months,

1-5-10 years post donation, then every 10 years, lifelong

• Follow-Up check by means of donor questionnaire and physician

review questionnaire, full blood count at FU 1 month for bone

marrow (BM) and peripheral stem cell donation (PBSC), later only

for PBSC

• FU for URD was performed either by the donor centres (regional

transfusion service (RTS) or SBSC, RD were followed at the

collection centres, which were – for most donors – identical with

the transplant centres (!)




Data collected include:

• donor details: age, gender, weight, D/R relationship

• type of collection (BM, PBSC, DLI), number of donations

• pre-exisiting health disorders

• type and dosage of growth factors

• complications during and after collection

• short and long-term follow-up data




Period 2: as of September 1st, 2013 modification of the sequence and

content of follow-up (consensus of the 1st international workshop

on donor outcome, 2009)*

• New time-points of data collection: time of harvest, 1m, 6m, 1y, then

2-4-6-8-10 years after donation, then every 10 years, lifelong

• FollowUp procedure remained the same in principle, but with introduction

of a «minimal data set» :

shortened questionnaire hoping to facilitate and encourage other

countries to enter their data into the database Promise

focus on the occurrence of any malignancy (haematological and

non-haematological), any autoimmune disease and

Severe adverse events in temporal association with donation

• 1m FUP in collection centre, from 6m onwards through SBSC

• FollowUp now limited to 10 years (new ordinance of Tx law Nov.2017)

*Halter et al, 2015: Allogeneic hematopoietic stem cell donation: standardized assessment of donor outcome

data . A WBMT consensus document



Between 01.07.2007 and 30.06.2017, 1209 blood stem cell donations

were performed in the 4 collection centres (CC) in CH (BS, GE, ZH, ZHpaeds)

Donation characteristics

All Related donors Unrelated donors

Number of donations 1209 893 316

1st donations 1105 802 (90%) 303 (95.6%)

2nd donations 88 76 (8%) 12 (4.1%)

3rd donations 16 15 (2%) 1 (0.3%)

Stem cell source

BM: all donations 229 164 (18%) 65 (21%)

PB: all donations 926 683 (77%) 243 (77%)

DLI: all donations 54 46 (5%) 8 (2%)

Data on DLI donations only collected since September 2013



Donor characteristics

All Related donors Unrelated donors

Gender:

female 565 (47%) 439 (49%) 126 (40%)

male 644 (53%) 454 (51%) 190 (60%)

Age (1st donations)

median 49y 34y

range 6mo – 74y 19 – 57y

RD: D/R relationship All PBSC (%) BM (%)

Identical sibling 647 (81%) 551 (85%) 96 (15%)

Matched other relative 6 (0.7%) 3 (50%) 3 (50%)

Mismatched/haploident.

relative141 (17.3%) 86 (61%) 55 (39%)

syngeneic 8 (1%) 8 0

802 648 154


Results




First donations and gender

Proportion of male to female donors overall: 53% vs 47% (n=1209)

36%

36%

17%

11%

RD / URD and gender, 1st donations, n=802/303

RD male

RD female

URD male

URD female

50%

50%

50%

40%

60%



Gender and source, first donations

1st donations RD/URD, gender and source

RD male PB

RD male BM

RD female PB

RD female BM

URD male PB

URD male BM

URD female PB

URD female BM

RD URD

male female male female

PB BM PB BM PB BM PB BM

83% 17% 79% 21% 80% 20% 78% 22%



Donations per year

0

10

20

30

40

50

60

70

80

90

nu

mb

er

of

do

nati

on

s

Number of first donations per year 2007-2017

RD PB

RD BM

URD PB

URD BM



Donations per collection centre

CCs 1,2,and 3 collect from RD and URD, CC4 only RD

Distribution (%) of collection types equal

265

203

168

12

3523

49 47

76

106

47

2433

6

0

50

100

150

200

250

300

1 2 3 4

Donations by collection centre

RD PB

RD BM

URD PB

URD BM

Remberger et al,

BMT 2015

B.Shaw et al,

BBMT 2015



CVC significantly more frequent in female donors: 14% of RD vs 8% of

URD, 6% and 1 % of the male RD and URD resp..

No SAEs reported

PBSC collection details: venous access

90%

10%

Venous access in %, RD

peripheral

CVC

92 %

8 %

Venous access in %, URD

peripheral

CVC



PBSC mobilisation details

73%

24%

Stem cell mobilisation, RD

Filgrastim

Lenograstim

81%

19%

Stem cell mobilisation, URD

Filgrastim

Lenograstim

• 648 RD PBSC donations, 240 URD PBSC donations

• Although doses per injection vary widely from centre to centre, most

donors received a dose close to the recommended daily dose of

10 μg/kg BW applied in 2 doses per day and with a total of 8 or 9 doses

• Mean body weight for both RD and URD: 75 kg each, range 38-160 kg for RD

and 50-118 kg for URD

• Use of Biosimilars and Plerixafor permitted since Nov. 2017→ adapted FU



• Of the 217 first bone marrow collections, 154 (71%) were

performed on RD and 63 (29%) on URD

• Anaesthesia and prior autologous blood donation:

BM collection details (1st donations)

RD URD

General anaesthesia 149 (97%) 61 (97%)

Epidural anaesthesia 5 (3%) 2 (3%)

Autologous blood donation before 27 (18%) 39 (62%)

Autologous blood retransfused 94% 92.5%

No donor received an allo-transfusion.

No difference in mobilisation or collection practise between

related and unrelated donors



Subsequent donations

A total of 88 second and 16 third donations were performed – a second

donation by 76 related and 12 unrelated donors, 15 related donors and

1 unrelated donor donated a third time.

RD (%) URD (%)

All PBSC BM DLI PBSC BM DLI

2nd donations 8831

(41%)

9 (12%)

36 (47%)

3 (25%)

1 (8%)

8 (67%)

3rd donations 164

(25%)

1(6%)

10(63%)

1 (6%)

FU-data on DLI donations only collected since 1st September, 2013



Donor age (1)

0

20

40

60

80

100

120

140

160

180

200

220

240

Number of related and unrelated donors at BM and PBSC by age, first donations

PB related

BM related

PB unrelated

BM unrelated



Donor age (2)

Median age of RD was 15 years

higher than URD: 48y vs 33 y

for all first donations (p< 0,0001)

Range URD: 19 – 57y

Range RD: 6 months – 74y

No age limit for RD

URD:

• 70% of all donors < 40 y old, 40% aged 18-30y

• 69% of PBSC donations from < 40y old, 43% aged18-30y, 26% aged 30-40y

RD:

• 75% of PBSC collected from donors > 40y

• Majority of PBSC donors aged 40-60y (58%); 33% aged 50-60, 16% aged 60-70

• 16% of all RDs > 60y old, 82% donated PBSC

• 40% of BM collections performed on children between 6 months and 18y

0

20

40

60

80

100

120

140

160

180

200

220

240

Number of related and unrelated donors at BM and PBSC by age, first donations

PB related

BM related

PB unrelated

BM unrelated



Pre-existing health disorders were significantly more frequent

in related donors (p<0.0001)

• RD: 25% (197/802 first donations, 283 problems)

• URD: 9% (27 /303 first donations, 31 problems)

Pre-existing health disorders (1)

Disorders RD (%) URD (%) Disorders RD (%) URD (%)

(Cardio)-vascular 86 (30) 6 (19) Gastro-intestinal, liver 12 (4.5) 2 (6)

Endocrine & metabolic 55 (19.5) 5 (16) Neurological 11 (4) 3 (10)

Haematologic 28 (10) 0 Autoimmune 10 (3.5) 2 (6)

Pulmonary 18 (6) 7 (23) Oncological 7 (2.5) 0

Psychological 17 (6) 2 (6) Other 28 (10) 4 (13)

Genito-urinary 11 (4) 0


Disorders RD (%) URD (%) Disorders RD (%) URD (%)

(Cardio-)vascular 86 (30) 6 (19) Gastro-intestinal, liver 12 (4.5) 2 (6)

Endocrine & metabolic 55 (19.5) 5 (16) Neurological 11 (4) 3 (10)

Haematologic 28 (10) 0 Autoimmune 10 (3.5) 2 (6)

Pulmonary 18 (6) 7 (23) Oncological 7 (2.5) 0

Psychological 17 (6) 2 (6) Other 28 (10) 4 (13)

Genito-urinary 11 (4) 0


Pre-existing health disorders were significantly more

frequent in related donors p<0.0001

• RD: 25% (197/802 first donations, 283 problems)

• URD: 9% (26/303 first donations, 31 problems)




Pre-existing health disorders RD URD

Cardiovascular 86 (30%) 6 (19%)

Arterial hypertension 72 5

Aortic aneurysm, aortic dissection, carotid aneurysm (post clipping),cerebral aneurysm,

aortic stenosis (2)6

Arrhythmia 1

Brugada syndrome/AV-block lI /cardiomyopathy / history of ischaemic stroke (1 each),

PAOD (3)7 1

Metabolic + Endocrinological 55 (20%) 5 (16%)

Diabetes 14 1

Hypothyroidism (8), struma nodosa (2), M.Hashimoto (2), M.Basedow (1) 13 2

Dyslipidaemia (23),Vit.D deficiency (1),Vit.B12-deficiency (1), disorder of phosphorus

metabolism (1),Gilbert’s syndrome (2)26 2

Benign neoplasm endocrine gland (2) 2

Haematological 28 (10%) 0

Iron deficiency (& anaemia), anaemia not specified (2) 7

Thalassaemia minor (5), thalassaemia carrier (2), Sickle cell disease carrier (2) 9

Thrombophilia with history of VTE (thrombosis, thrombophlebitis, pulmonary embolism) 5

Haemochromatosis (3), v.Willebrand disease, protein C deficiency(without thrombosis),

CD4/8 T-cell population of unknown significance, ongoing anticoagulation (1 each)7

Autoimmune, immune 10 (3%) 2(6%)

Psoriasis, psoriasis arthritis (3), Neurodermitis (2), Vitiligo (2), Pityriasis rosea (1) 8

M.Bechterew (1) 1

Allergies (pollen, medical drugs) 1 2

Pulmonary (18/7), Psychological (17/2), Genito-urinary (11/0), Neurological (11/3), Gastro-intestinal

(12/2), Oncological (7/0), Other (28/4)




Harvest related complications: RD: 28 (3.5%), URD 5 (2%)

• Corresponding to the known acute toxicities of the donation procedures

Severe adverse events (SAE), first donations

SAEs related to donation procedure: RD: 8 (0.9%), URD: 2 (0.6%)

SAE Total Related donors Total Unrelated donors

PBSC 5 Hypocalcaemic tetany 2 Chest oppression after collection

Arterial hypertension Vasovagal reactions during G-

CSF, before collection

Angioedema

Ventricular arrhythmia,

extrasystoles

Severe musculoskeletal pain

BM 3 Bilateral deep vein

thrombosis,

Broncho-/laryngospasm

during intubation

Fever, need for antibiotics



Elderly donors, health disorders

• Children and elderly donors with comorbidities are more vulnerable compared to

URD who are significantly younger and (by definition) healthy.

• roughly 30% of related donors would have been deferred as URD

• «Acceptable risk» is on a higher level for RD

• However: complications associated with donation procedure were moderate

and in keeping with known side effects of donation procedures

• Few SAEs associated with donation procedure (< 1%) (Halter et al, 2009, 2013)

Donation process seems to be safe !

Pre-donation medical assessment is all the more important / must be carefully &

appropriately done / individually adapted screening to ensure donor safety !

Eligibility criteria for RD less strict, less definite, great variety

consensus statement following 3rd Donor Outcome WS in 2013: (N. Worel, BBMT ,2015)

• Who is the better donor ? older matched sibling vs younger matched URD ? **• MSD still first choice (if available), despite some drawbacks (mob., pat.outcome)

• If matched unrelated donor (MUD) chosen, younger donors are preferred ***

**Switzer QoLstudy, BBMT 2017

***Shaw et al, BBMT 2018



Short term follow-up, ≤ 1 year

FollowUp RD URD

1 month

64 (8%, 7 BM, 57 PBSC)

Approx. 50% residual pain and fatigue,

respiratory, gastro-intestinal, psycho-

logical complaints

22 (7%, 9 BM, 13 PBSC)

Similar problems, pain more linked

to BM collection

SAE 1 chest pain, 1Takasayu arteriitis -

6 months

43 (5.3%, 7 BM, 34 PBSC)

~ 20% pain and fatigue, resp. tract

infections, (increased)asthma, GI-

(gastritis, gastroenteritis), 1 nephritis

14 (4.6%, 5 BM, 9 PBSC)

Similar problems, 1 dental

abscess

SAE2 myocardial infarctions (3 and 6 mo

post-don), 1 MGUS-

1 year

34 (4.2%, 8 BM, 26 PBSC)

Infections (13, resp > UTI> GI), pain

and fatigue, iron def. anaemia

2 (0.6%, 1BM, 1 PBSC)

Back pain, 1 strep. infection

SAE 1 melanoma -



Long term follow-up: >1year

Time after

don.RD URD

1 year 1 melanoma, 1 breast cancer

1 bronchial asthma, 1 cardial infarction

1 colitis ulcerosa & 1 autoimmune thyroiditis

1 MGUS

2 years 1 prostate cancer

4 years 1 prostate cancer1 probable autoimmune disease

(seroneg. arthritis)*

5 years 1 basalioma

1 (MGUS) 1 glioblastoma, donor deceased

6 years 1 basalioma

1 benign neoplasm of the brain

1 Sjögren syndrome

8 years 1 M.Crohn 1 papillary digital adenocarcinoma

RD: 16 events after first donations: 2.0 % (cancers 0.6%, 5/802)

URD: 2 events 0.6% / 1 cancer : 0.3%

RD&URD: 1.6%



FollowUp during 1st year after donation, URD

0

20

40

60

80

100

120

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

URD FU in first year after donation

1m

6m

1y



FollowUp during 1st year after donation, RD

0

10

20

30

40

50

60

70

80

90

100

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

RD FU in first year after donation

1m

6m

1y



Development of FollowUp 2014 - 2016


Conclusions


• Donor characteristics differ significantly between related and unrelated

donors concerning age and pre-exisiting health disorders

need for standardised follow-up for RD

need for standardised eligibility criteria for RD

• Harvest-related toxicities moderate, SAEs for RD and URD < 1 %

• HSCT can be performed safely on elderly donors provided screening and

management is individually adapted

• Long-term FU: SAEs in RD 2.1%, URD: 0.6% (1st donations)

• Donor FU is now very good at 1 month for both RD and URD

solid basis for assessing complications up to 30 days post-donation

FUP for RD improving and increasing. Often much appreciated by RD

• Centralising FUP management in the registry is a great advantage with

regards to standardisation/ harmonisation, automation and saving

ressources


Thanks to

Partners, contact persons

Regional Blood Transfusion Services

Collection Centres

Transplant Centres

Datamanagers ProMise (esp. Eva Buhrfeind)

FollowUp Team SBSC

Grazia Nicoloso

Jörg Halter, USB

elisabeth.gobet, sarah.morin, estelle.brioudes,

celine.nancoz, martine.grandgirard, reinhard.henschler,

anne-catherine.berclaz, markus.jutzi, annlea.vogel,

martina.mendanova, doris.haendeler, andrea.depfner

antoniamaria.mueller, pascale.bindschedler,

nathalie.bochudbeaud, rahel.boehlen, jean.villard,

barbara.piccolruaz, stefano.barelli, ursula.cloux,

nicole.jastrowmeyer, virginie.morin, ayseozlem.hizarci

cabinet.plaschy, sophie.waldvogelabramowski,

veronique.chapuis, jana.rosochova, andreas.buser

judith.ries, stavroula.masouridi, ulrike.zeilhofer,

gayathri.nair, myriam.zihlmann, daniele.junod,

heidi.althaus, andreas.holbro, elisabeth.mathier,

saadia.huguet, yves.chalandon, tina.weingand,

urs.schanz, deborah.schneider, tayfun.guengoer,

jakob.passweg, joerg.halter, dominik.heim,

joerg.sigle, charlotte.wehrli, mario.bargetzi,

stefano.fontana, doris.neuhaus, laura.infanti,

pyves.lovey, joelle.vuignier, gabrielle.allemann,

bm.frey, kata.sunic, jutta.thierbach, mauro.borri,

angela castracane, damiano.castelli, amira.sarraj,

hedy.arnoldabipour, heidi lüscher, edith.lagler,

antonella.buccolo, anne-claire.mamez, paolo

tiraboschi, jean-marie.tiercy, eva.buhrfeind

sonja.heer, ruth.seidlitz, helen.baldomero, elif.guel,

anna.petropoulou, mathias hauri, tabea.stadlin,

therese.lopez, nicole heim, muriel.quilleau,

emmanuel.levrat, sandra.perroude, nathalie.ferre,

monique.hess, agnes.besançon, carmen.ruiz,

katharina.ritter, tizian.demont


Blutspende SRK Schweiz AG

Laupenstrasse 37, Postfach 5510, 3001 BernTel: +41 (0)31 380 81 81, Fax: +41 (0)31 380 81 [email protected], www.sbsc.ch

Morven Rüesch, med. pract.Medical serviceTel: +41 (0)31 380 81 [email protected]

Thank you for your attention



Types of subsequent donations (1)

Related donors Unrelated donors

1st don type 2nd don type2nd don

number3rd don type

3rd don

number

2nd don

number

3rd don

number

BM BM 2

BM PB 8 2

BM DLI 4 3

PB BM 7 1

PB PB 23 DLI 2 1

BM 1

PB DLI 32 DLI 8 5

PB 4

? ? BM 1



Types of subsequent donations (2)

1

4

3

2 2 2

0

1

2

3

4

5

1 2 3 5 8 >8

Interval between 2nd and 3rd donation in months (RD)

Related donors: • 0-6m: 12 DLI, 10 PB, 2 BM

• 7-12m: 12 DLI, 4 PB

• Year 2: 2 DLI, 9 PB, 3 BM

• Year 3: 4 DLI, 2 PB, 3 BM

• Year 4: 2 DLI, 2 PB

• > 4y: 4 DLI, 4 PB, 1 BM

Unrelated donors:

• 0-6m: 2 DLI, 1 PB, 1 BM

• 7-12m: 3 DLI, 1 PB

• Year 2: 2 DLI

• Year 4: 1 PB

• > 4y: 1 DLI

24

1614

9

4

9

0

5

10

15

20

25

30

0-6 7-12 13-24 25-36 37-48 >48

Interval between 1st and 2nd donation in months (RD)



Donor age (3)

• 453 sibling donors, 313 BM (69%), 140 PBSC (31%)

• Moderate side effects after BM collection, no severe complications.

• Complications mainly related to anaesthesia (vomiting, cardiovascular)

• CVC-placement in 81 PBSC donors, 1 SAE (pneumothorax with hydrothorax)

• Blood transfusions:

• 28% of BM-donors received autologous blood transfusion

• 27% of BM donors (84) and 9 (6%) PBSC donors received RBC allo-transfusion

• Risk for need of allotransfusion: age < 4y and volume collected >20 ml/kg

SAEs in healthy paediatric donors are rare, no statistical difference

between BM and PBSC



Donor age (3)

RD:

• children and elderly donors are more vulnerable compared to URD who

are significantly younger and (by definition) healthy.

• BM is the primary blood stem cell source for paediatric recipients

• Of the 67 donations performed by children, 62 were BM (93%), only 5 PB

• BM donation is regarded as safe - nevertheless, sibling donors are

exposed to general or spinal anaesthesia, potential CVC placement,

blood loss and potential blood transfusion (auto- or allo-)

• Study by EBMT Paediatric Diseases Working Party, 2005-2009

• Our data: no SAE reported after paediatric donations



Donor age (3)

• Study on Health Related Quality of Life in paediatric HSC donors*

• HRQoL in first year after donation, assessed with score system, compared

to children in «normal» population who had not donated

- approx. 20% of donors had poor HRQoL during 1st year after donation

- younger children were at particular risk of poor HRQoL

- child self-reported HRQoL was significantly lower than parent

proxy-reported HRQoL

Need for more psycho-social support for siblings after donation ?

Should parents be more sensitised to the needs of donor siblings ?

• Recommendations for the determination of eligibilty in related paediatric

HSC donors with focus on ethical and clinical considerations**

• FUP will be continued for paediatric donors until 18 years old

* Switzer et al,2016 , ** M.Bitan et al, BBMT 2016,

Consensus Workshop 2013

10 years prospective donor follow-up in switzerland · hilfslinien anzeigen über menu: donor...

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