ANZTCT Guidelines Cell Therapy Guidelines

Suitability guidelines for related haemopoietic progenitor cell donors

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Background

Assessment of the suitability of allogeneic donors to donate haemopoietic progenitor cells (HPC) involves consideration of both risk to the donor from donation, as well as potential risk of the transmission of infectious and other disease to the recipient.  While the ABMDR provides guidance for unrelated donor assessment, suitability criteria are often different for related donors, as there may be a higher tolerance for risk to both donor and recipient.  This guideline provides consensus recommendations for related HPC donor assessment in Australia and New Zealand. Donor conditions are grouped according to relevance to either donor or recipient safety.  The recommendations are based on available guidelines, which are also summarised.

It should be noted that legislation exists in each State and Territory regarding when children can and cannot act as an allogeneic HPC donor. It is essential that donor physicians are aware of relevant legislation both because this differs between jurisdictions and because it differs according to the child’s capacity to understand the nature of what is being asked of them.

It is acknowledged that determination of donor suitability relies on the clinical judgement of the physician responsible for the assessment.  The recommendations provided in this document serve only as a guideline to assist this process.  Where donor assessment identifies circumstances not addressed in these guidelines, discussion with other practitioners involved in donor assessment, including the authors of this document, is encouraged.

Abbreviations

ABMDRAustralian Bone Marrow Donor Registry
ASA-PSAmerican Society of Anesthesiologists – Physical Status classification system
BCCBasal cell carcinoma
BMBone marrow
B thalBeta thalassaemia
CJDCreutzfeldt-Jakob disease
CKDChronic kidney disease
DMDiabetes mellitus
GAGeneral anaesthetic
GFRGlomerular filtration rate
HbSSickle cell disease
MBLMonoclonal B-cell lymphocytosis
MGUSMonoclonal gammopathy of uncertain significance
NAFLDNon-alcoholic fatty liver disease
NPAACNational Pathology Accreditation Advisory Council
IDUInjecting drug use
ISTImmunosuppression therapy
SCCSquamous cell carcinoma
SLESystemic lupus erythematosus
TGATherapeutic Goods Administration
TGO88Therapeutic Goods Order No. 88
WBMTWorldwide Network for Blood and Marrow Transplantation
WMDAWorld Marrow Donor Association

Definitions

Ineligible – an allogeneic cellular therapy product donor who has identified risk factor(s) for relevant communicable diseases.  Such donors may be suitable to proceed with donation, at the discretion of the recipient transplant physician, who should discuss this risk with the recipient. NPAAC standards regarding management of ‘non-conforming’ donors and products would apply to such donors.

Policy

Related donors should be assessed by a medical practitioner who does not have primary responsibility for the recipient (third party haematologist).  Final responsibility for all donor care, including follow-up of results and referral for medical care if appropriate, rests with the donor’s medical team, and not with the recipient transplant physician.

It is imperative that confidentiality be maintained regarding all aspects of donor care.  Where a donor is deemed unacceptable based on a medical condition, the recipient should not be informed of the reason without the donor’s consent.  If a donor declines to donate, the same information (e.g. “not suitable due to medical reasons”) should be provided to the recipient.  Where a potential communicable disease risk is identified in the donor, consent must be obtained from the donor before this can be disclosed to the recipient.

In all cases HPC donation should proceed only with the consent of the donor or, where the donor lacks legal capacity, with the consent of the donor’s substitute decision-maker. Most importantly, in these situations the decision to donate should always be voluntary and not be coerced.

Conditions most relevant to donor safety

CriterionTGO88ABMDR (unrelated donors)WBMT (related donors)ANZTCT Recommendation
AgeNeed limits18-60yrNilAcceptable: 14-75, with extra criteria for minors and elderly (below).
BMINil<35 assess for fitness for GA & venous access≤40Acceptable ≤40; not acceptable for BM if >40.
Heart diseaseNilDiscretion of 3rd party haematologistUse ASA-PS & other risk assessment tools. Refer to cardiologist.Discretion of 3rd party haematologist, consider consultation with cardiologist.
ThrombosisNilNilIf anticoagulation no longer indicated.Accept if anticoagulation no longer indicated or temporary cessation considered acceptable  Consider role of prophylaxis in at-risk donors post G-CSF or BM harvest
StrokeNilPermanent deferralDiscretion of 3rd party haematologist.Generally not acceptable
Cognitive impairmentNilPermanent deferralDonor advocate, consider cryopreservation.Donor advocate involvement prior to HLA typing, consider cryopreservation.
Sickle cell diseaseNilPermanent deferralAvoid G-CSF in HbS, HbS/B thal.Avoid G-CSF in sickle cell disease.
Autoimmune diseaseNilG-CSF may be contraindicatedDefer if systemic autoimmune disease. Defer if on pred >5mg or other IST. Avoid G-CSF in inflammatory joint disease.Avoid G-CSF in inflammatory joint disease. If systemic autoimmune disease, discuss with recipient physician.  Also note possibility of disease transmission to recipient (also relevant to recipient safety).
Severe back pain, back surgeryNilNilAvoid BM harvestAvoid BM harvest in general, discuss with anaesthetist if considering proceeding.
GoutNilNilAvoid G-CSFAcceptable with donor consent.
Diabetes mellitusNilNilAssess late effectsAcceptable (but assess end organ damage).
Kidney diseaseNilPermanent deferral for autoimmune or infectious CKDDefer if associated with chronic infection, DM, SLE or GFR < 30.Not acceptable if GFR < 30 (Cockroft-Gault calculation).
EpilepsyNilDefer if < 3yr post seizureAccept if allowed to drive.Discretion of 3rd party haematologist, discuss with neurologist.
BreastfeedingNilG-CSF: express & discard until 7 days post dose BM: Express & discard until 24hr post GAExpress & discard until 24 hr post G-CSF or GA.G-CSF: express & discard until 7 days post dose BM: Express & discard until 24hr post GA.
PregnantNilDeferDeferDefer
Liver diseaseNilDefer for hepatic failure.Deranged LFT, ? cause: defer until cause known. NAFLD: suitable. Cirrhosis: not acceptable if Child-Pugh B or C.Deranged LFT, uncertain cause: defer until cause known. NAFLD: suitable. Cirrhosis: not acceptable if Child-Pugh Score B or C.
SplenomegalyNilNilAcceptable depending on cause. Expect 10-15% increase in spleen size.Acceptable depending on cause. Generally, BM collection preferred. Monitor closely if G-CSF given.
RespiratoryNilDefer for respiratory failure.Asthma: acceptable if not on oral steroids Cough or dyspnoea at rest: not suitable.Discretion of 3rd party haematologist, consider consultation with respiratory physician.
Anaesthetic riskNilInform anaesthetist.Avoid BM (GA) if >ASA P2.Discuss with anaesthetist.

Criteria for the use of children as donors (<14 years)

  1. No medically equivalent adult related donor.
  2. After evaluation, staff deem a strong personal and emotionally positive relationship exists between donor and recipient.
  3. Parental consent and donor assent generally required.  Where required by law approval should also be sought from relevant State committee.
  4. All care should be provided by a paediatric service with experience in management of HPC donors.

Criteria for the use of a minor donor (14-17yrs):

  1. No medically equivalent adult related donor.
  2. After evaluation, staff deem a strong personal and emotionally positive relationship exists between donor and recipient.
  3. Parental consent and donor assent generally required.  Where donor is deemed able to provide consent, a parent or guardian will co-sign.  Where required by law approval should also be sought from relevant State committee. Discussion with a paediatric transplant physician regarding requirements for donor consent is recommended.
  4. Donors being managed at adult facilities should weigh > 35kg.
  5. Donors 14-17 considered to require specialised paediatric management should be referred to a paediatric service for assessment and collection. This should be considered prior to HLA typing for these donors.

Criteria for the use of an elderly donor (65 – 75yrs):

  1. Must meet suitability criteria.
  2. Comorbidities must be identified and a management plan identified for each.
  3. Performance status must permit safe collection of cells.
  4. Resources must be provided for disabilities, including visual or hearing impairments.
  5. Prefer HPC-A collection over HPC-M harvest.
  6. Careful consideration should be given to the possibility of inadequate mobilisation. In high risk cases, collection and cryopreservation prior to the recipient commencing chemotherapy may be considered.

Conditions most relevant to recipient safety

CriterionTGO88ABMDR (unrelated donors)WBMT (related donors)ANZTCT Recommendation
Malignancy (excluding SCC, BCC, cervical CIN)NilAccept if ≥5 years post ‘cure’ Permanent deferral for haem malignancy.Accept if 5-10 years post remission. Permanent deferral for haem malignancy. Note MBL and MGUS not included.Accept if 5 years post remission, but discuss with recipient physician if any systemic chemotherapy due to MDS/AML risk. Haem malignancy not acceptable. MBL or MGUS generally not acceptable.
Cytopenias (unexplained)NilNilAccept if: Neutrophils >1.0 Lymphocytes >0.5, Platelets >100 Hb within 20 of LLNBMAT + cytogenetics if: Neutrophils <2.0 (and not African) Platelets < 130 Consider testing for germline mutations (incl. RUNX1, CEBPA, p53), particularly if family history of AML/MDS, thrombocytopenia, BM failure or familial cancer syndromes
Drug userIneligible for 5 years from last injectionPermanent deferral if any prior IDU.Permanent deferral if IDU Consider cryopreservation for othersIneligible for 5 years from last injection. Consider cryopreservation for any drug user.
Prison inmate > 72 hoursIneligible until 12 months post releaseDefer until 12 months post release.NilIneligible until 6 months post release.
‘High risk’ sexual practiceIneligible until 12 months from last contactDefer until 12 months from last contact.NilIneligible until 6 months from last contact.
Needle-stick, tattoo, piercingIneligible until 6 months post exposure, or 4 months if HCV NAT negativeDefer until 4 months post exposure.NilIneligible until 4 months post exposure.
Non-human graft, history of CJD, human pituitary hormonePermanently ineligiblePermanent deferralDiscretion of 3rd party haematologistIneligible donor, discuss with recipient physician
Corneal, organ or BM transplantNilPermanent deferralNilCorneal: ineligibleBM: generally not acceptable Solid organ: generally not acceptable.
HIV or HTLV1Permanently ineligiblePermanent deferralNilNot acceptable.
Hep B, Hep CIneligible until non-infected state establishedNotify transplant centreNilIneligible donor, discuss with recipient physician
History of malariaIneligible until negative immunological test ≥120 days post completion of therapyPerform immunological test and notify transplant centre if <120 days post treatment.NilIneligible until negative immunological test ≥120 days post completion of therapy.
Travel to malaria risk areaAccept if > 12 months ago. Accept if negative immunological test ≥120 days after travelPerform immunological test and notify transplant centre if <120 days post exposure.NilNeed immunological test if exposure within last 12 months.  Ineligible until negative immunological test ≥120 days post exposure.
History of meningitisNilPermanent deferralAcceptAcceptable
Active bacterial infectionNilOsteomyelitis: accept if <2 years after ‘cure’.Osteomyelitis: accept if ‘cured’Acceptable if treatment completed.
History of ZikaNilDisclose to transplant centre if <4 months since recovery.NilIneligible until 4 months post recovery.
Contact with ZikaNilDisclose to transplant centre if sexual contact.NilIneligible until 6 months post exposure.
Travel to Zika risk areaNilDengue/arbovirus policy applies – disclose to transplant centre if travel was less than 4 weeks prior to collection date.NilIneligible until 6 months post exposure.
Live attenuated vaccine (MMR, Varivax, Zostavax, BCG, oral cholera, oral typhoid fever)Ineligible if within 4 weeksDefer 4 weeksNilIneligible if within 4 weeks.

Sources

  1. Therapeutic Goods Order No. 88 – Standards for donor selection, testing and minimizing infectious disease transmission via therapeutic goods that are human blood and blood products, human tissues and human cellular therapy products.  Australian Government Department of Health and Aging.  20th May 2013.
  2. Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products.  US Department of Health and Human Services, Food and Drug Administration.  March 2016.
  3. Australian Bone Marrow Donor Registry Standard: Donor Health Assessment and Infectious Disease Testing (ABMDR-STD-OP-006-11), Sept 2016.
  4. National Pathology Accreditation Advisory Council: Requirements for Procedures Related to the Collection, Processing, Storage and Issue of Human Haemopoietic Progenitor Cells (Fifth Edition 2015)
  5. Worel N, Buser A, Greinix H, Hagglund H, Navarro W, Pulsipher M et al.  Suitability Criteria for Adult Related Donors: A Consensus Statement from the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues.  BBMT 2015; 21: 2052-2060.
  6. Pitt V et al.  Review of Australian Blood Donor Deferrals Relating to Sexual Activity. Commissioned by Australian Red Cross Blood Service.  May 2012.
  7. Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products.  US Department of Health and Human Services, Food and Drug Administration.  March 2016.