Donor outcome

follow up

Joerg Halter

University Hospital Basel

Switzerland

background

1 allogeneic HSCT = 2 individuals involved

• Numbers of allogeneic HSCT are still increasing

• Need for both, related and unrelated volunteer donors is increasing

Why do we need donor outcome follow up?

– Need for INFORMED consent of donors

– Need for maximum donor safety, taking into account, that:

• Number of donors is increasing

• Number of elderly patients (with elderly siblings) is increasing

• Results from and access to alternative transplants (URD,

haplo, CB) improve and will likely to improve further

– To maintain current high donor motivation it is essential that

donors can fully rely on best care

– Donation procedures are associated with adverse effects

endorsed by the sixty-third World Health Assembly in May 2010, in Resolution WHA63.22. Document WHA63/2010/REC/1, Annex 8

HSC donors: more than just the source of

HSC and therapeutic cells

general-(spinal-)

anaesthesia

multiple punctures from

both iliac crest

pretreatment with G-CSF

maybe need for CVC

anticoagulation during

apheresis

punction of umbilical

vein after delivery

Frequent adverse events:

pain, fatigue, insomnia, nausea

risks and serious adverse events associated with the donation

process

With bone marrow donation:

• Associated with risks of anaesthesia: Arrhythmias with/without

cardiac arrest, myocardial infarction, stroke, pulmonary edema, PE,

malignant hyperthermia, anaphylaxis

• Local complications: wound infection, fractures, nerve, bone or

tissue injury, chronic pain

• (need for allogeneic transfusion)

With PBSC donation:

• Associated with biologic actions of G-CSF: Allergic

reactions/anaphylaxis, splenic rupture, respiratory distress/acute

lung injury, triggering of inflammatory diseases, thrombosis (arterial,

venous), Sickle cell crisis

• Catheter-related: Bleeding, thrombosis, pneumo-/hematothorax

• Related to apheresis procedure: Hypocalcemia,

thrombocytopenia/anticoagulation, need for priming with allogeneic

blood

Höllig et al. Blood 2009, Kodera et al. EBMT 2008, Miller et al. BBMT 2008/ Pulsipher et al. Blood 2009,

Halter et al. Haematologica 2009, Confer DL. Hematology 2009 & NOTIFY 2011, Styczynski J et al.Blood 2012

DKMS JSHCT NMDP EBMT EBMT ped

design n BM n PB

prospective --

3928

prospective 5921 3264

prospective 9245 7850

retrospective 27770 23254

prospective 313 140

BM -- 0.37% 1.35% 0.04% --

PB <0.1% 0.61% 0.5-0.6% 0.11% 0.7%

Höllig et al. Blood 2009, Kodera et al. EBMT 2008, Miller et al. BBMT 2008/ Pulsipher et al. Blood 2009, Halter et al. Haematologica

2009, Styczynski J et al.Blood 2012

Open issues

• Frequency of SAR?

• Are there differences:

• between related and unrelated donors?

• after one or multiple donations?

Fatal events in temporal association with donation procedure

BM PB published

EBMT 1 LE 1 error 1 SDH 2 cardiac

0/5

US 4 cardiac 1 respiratory arrest 1 PE

1 cardiac 1 Stroke 1 sickle cell crisis

3 (4?)/9

JSHCT (1) CNS 0 0

South America

1 intracerebral bleeding abstract

WMDA 1 hemato-pneumothorax alert

Risk: ?

→ Causality? Risk factors?

Donor data:

•Donor ID

•Age at donation

•Sex

•Relationship to the recipient: twin, sibling, other family donor,

unrelated donor

Harvest data

•Start date of the procedure

•Was the product collection completed? → yes/no

•Number of harvest/subsequent donation

•Were hematopoietic growth factors used (eg. GCSF)? → yes/no

•Were cell binding inhibitors used (eg. plerixafor)? → yes/no

•Was erythropoietin used? → yes/no

•Were other drugs used for mobilization (without further

specification)? → yes/no

Product:

BM (including harvest of MSC), PBSC, both, unstimulated

leucapheresis (eg. DLI), others

Donor characteristics and procedure related data

Complications in temporal association with the donation procedure:

•report only serious adverse reactions (SAR)

definition of SAE is the same as in WMDA and includes:

•Death (ICD code)

•life-threatening event (ICD code)

•require in-patient hospitalization or prolongation of existing

hospitalization due to WHO grade 3 or 4 toxicity (ICD code)

•persistent or significant disability/incapacity (ICD code)

•every SAR occurring in the interval between start of the donation

procedure and day 30 after end of the procedure must be reported.

In most countries, these events have also to be reported to the authorities.

Adverse event reporting

Donor survival status

- Date of last follow up or death

- Donor alive? - if no: cause of death (ICD code) Malignancy

- Hematologic malignancy?

if yes: was diagnosis confirmed by medical data (ICD code)

- Non-hematologic malignancy?

if yes: was diagnosis confirmed by medical data (ICD code)

Autoimmune disease

-if yes: was diagnosis confirmed by medical data (ICD code)

Long term follow up

- up to 10 years after completion of the last donation procedure

- minimal reporting after 1 year, 5 years and 10 years but annual or

biannual reporting is recommended

3 items: survival status – malignancy – autoimmune disease

the future

• donor outcome follow up for all donors

• may be performed practically in different ways, but with identical

data sets

• donor outcome registries allow to define risk and eligibility criteria for

donors increase donor safety and contribute to decision making

• reimbursement for allogeneic transplant must include the outcome

follow up for two individuals: the patient and the donor, who makes the allogeneic HSCT possible

minimum dataset extended dataset Eligiblity criteria for

pediatric donors,

elderly donors and

donors with

comorbidities

2009 2011 2013