World Marrow Donor Association

Special report: Donor work-up and transport of bone marrow

Recommendations and requirements for a standardized practice throughout the world from the Donor Registries and Quality Assurance Working Groups of the World Marrow Donor Association (WMDA)

SA Cleaver¹, P Warren², M Kern³, CK Hurley^4*, C Raffoux^5*, J Keller⁶, U Kiesel⁷, V Koza⁸, E Marry⁵, A Mitterschiffthaler⁹, M Nakamura¹⁰, CT Okah¹¹, U Persson¹², T Radde-Stepaniak¹³, L Ranson⁵, J Raymond¹⁴, M do Rosario Sancho¹⁵, M Varla-Leftherioti¹⁶, T Wiegand¹⁴, J M Winterhager¹⁷ and DG Woodfield¹⁸

¹ Anthony Nolan Bone Marrow Trust, Royal Free Hospital, London, UK; ² Canadian Red Cross Society, Vancouver, Canada; ³ Swiss Bone Marrow Donor Registry, Berne, Switzerland; ⁴ Georgetown University, Washington DC, USA; ⁵ France Greffe de Moelle, Paris, France; ⁶ American Bone Marrow Donor Registry, LA, USA; ⁷ Bone Marrow Donor Center, Medical School of the Heinrich-Heine University, Dusseldorf, Germany; ⁸ Department of Hematology & Oncology, Charles University Hospital, Pilsen, Czech Republic; ⁹ Austrian Bone Marrow Donors, Vienna, Austria; ¹⁰ Japanese Red Cross Nagoya First Hospital, Japan; ¹¹ Tombra Life Support, Lagos, Nigeria; ¹² Tobias Registry of Swedish Bone Marrow Donors, Huddinge Hospital, Sweden; ¹³ National Marrow Donor Program, Minneapolis, USA; ¹⁴ The Caitlin Raymond International Registry, University of MA Medical Center, Worcester, USA; ¹⁵ Centro de Histocompatibilidade do Sul, Portugal; ¹⁶ Athens Bone Marrow Donor Registry, Greece; ¹⁷ Knochenmark-Spenderzentrale, Institut fuer Immunologie, Universitaetsklinikum Essen, Germany; and ¹⁸ Auckland Regional Blood Service, Auckland Hospital, New Zealand.

Summary:

In October 1995 the World Marrow Donor Association (WMDA) was restructured in order to facilitate its primary function of establishing guidelines in relation to international bone marrow and blood stem cell transplants - transplants in which the donor is in one country and the patient is in another country. Five new working groups were established - Donor Registries, Ethics, Quality Assurance, Finances, and Stem Cells. This paper, prepared by members of the Donor Registries Working Group, in consultation with the Quality Assurance Working Group, provides recommendations for the `donor work-up'. This term covers events that start when the definitive donor has been identified, includes the harvesting (collection) and transportation of the stem cell product and ends when the product reaches the transplant centre. The paper includes examples of the documentation intended to ensure compliance with the recommendations at all key points in the sequence.

Keywords: allogeneic bone marrow transplantation; volunteer unrelated donors; donor registries; marrow harvest; transportation; World Marrow Donor Association

Correspondence: Ms SA Cleaver, Anthony Nolan Bone Marrow Trust, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK.
The President of the WMDA is Prof Jon van Rood (Leiden, The Netherlands)
*Members of the Quality Assurance Working Group
Received 9 April 1997; accepted 23 June 1997

A primary function of the World Marrow Donor Association (WMDA) is to establish guidelines in relation to international bone marrow and blood stem cell transplants - transplants in which the donor is in one country and the patient in another country. This paper contains recommendations to promote efficient, consistent practice and communication between national registries (hubs), donor centres, harvest centres, and bone marrow couriers, in the work-up of volunteer unrelated donors in one country who have been requested to donate bone marrow to patients in another country. It covers the time period after selection of the definitive donor, through harvesting of the bone marrow, to transport of the bone marrow to its final destination of a transplant centre in another country. It outlines the responsibilities of the parties involved - national registry (hub), donor centre, harvest centre, and courier - in respect to the volunteer donor and in their interactions with one another with the ultimate goal to provide a quality product to the transplant centre in the timescale required.

1 National registry (hub) responsibilities

1.1 Checking donor selection criteria are met:

1.1.1 HLA typing (Figure 1):

(a) Donor and patient typing both received.
(b) Degree of testing and degree of HLA match is to level required by registry.
(c) All confirmatory testing of both patient and donor must have been performed at requesting transplant centre or in their affiliated laboratory.

1.1.2 Marrow prescription (Figure 2): The marrow prescription form must be checked for correct completion in its entirety.

1.1.3 Disease status: Confirm acceptability of disease status1, including preferred time to transplant.

1.1.4 Finances: Confirm ability to pay for transplant

1.2 Time to transplant

Ascertain/Designate Urgent or Standard Work-up

1.3Practicalities

Liaise between donor/ transplant centres and foreign hubs:

(a) Ensure all information is communicated in writing and in a timely fashion.
(b) Advise donor centres of donor identification (ID), marrow prescription, patient status and degree of urgency.
(c) Liaise over dates/progress of medical work-up in writing and confirm harvest details (date, time, venue, contact details).
(d) Advise of donor fitness to donate prior to commencement of patient conditioning, to comprise infectious disease marker (IDM) analysis (Figure 3), blood cell counts report, and a statement that the donor is eligible to donate.
(e) Confirm courier information (Figure 4), flight times, back-up flights (required for long distance transportations).
(f) Send to airport, letter facilitating the passage of the marrow through airport security, with copy to courier.
(g) Confirm hotel arrangements for couriers (make bookings for foreign couriers).
(h) Provide exact location of harvest centre and/or transplant centre and advise on transport/directions to and from airport and directions upon arrival at harvest and/or transplant centre.
(i) Obtain for the national courier, or relay to the foreign hub, the name, address, telefax number, work and private telephone numbers of the donor centre/harvest centre contact.

1.4 Insurance

Ensure all national donors are insured in compliance with national requirements.

1.5 Finances

Assume responsibility for payment/invoicing on a hub to hub basis.

1.6 Standards

Set national standards for speed of work-up, keep statistics on rate of donor attrition at work-up.

2 Donor centre responsibilities

2.1 Donor consent

(a) Establish donor willingness to donate - usually phone contact is appropriate due to time sensitivity.
(b) Ensure donor participates in information session and receives adequate counselling on procedures. The following items should be covered by donor centre and harvest centre staff:

• Emphasis on anonymity for donor and patient (discuss local regulations on whether total anonymity may be relaxed in time, and those of other countries that may differ ).
  
• Opportunity to discuss donation with a neutral person (donor advocate).
  
• Requirement for further blood samples before donation.
  
• Requirement for virological testing, especially HIV and HbsAG.
  
• Request for blood samples for research purposes (where Registry policy permits).
  
• Risks of anaesthesia and harvest procedure.
  
• Loss of time from normal activities.
  
• Location of harvest procedure, i.e. proximity to donor's home.
  
• Requirement for collection of autologous blood unit.
  
• Possibility of need for allogeneic unit and associated risks.
  
• Donor's right to withdraw and consequences for the patient if this right is exercised after the transplant protocol has started.
  
• Patient's need for BMT and chance of success expressed in general terms.
  
• Possibility of second donation for the same patient (including possibility of G-CSF if permitted locally, leucapheresis in case of relapse).
  
• Details of any compensation for loss of income, emphasising donation as a gift without remuneration and details of insurance cover effected.

2.2 Timing of transplant

(a) Advise national hub/transplant centre of any obvious difficulties in time-frame, e.g. donor going on holiday , harvest centre booking problems.
(b) Agree on harvest date with donor.

2.3 Donor medical requirements

(a) Arrange for assessment of donor's suitability to donate autologous blood units (this may be included in the physical examination).
(b) Identify any obvious difficulty in obtaining requested marrow cell count, and alert harvest centre and National Registry.
(c) Arrange for donor physical examination to assess suitability to donate bone marrow. The following investigations should be included:

• Medical history.
  
• Physical examination.
  
• Chest X-ray.
  
• ECG (if indicated and for all men over 40 and women over 50 years).
  
• Hb, full blood count and differential, with blood film.
  
• Blood group and antibody screen.
  
• Coagulation screen.
  
• Biochemical profile: urea, electrolytes, creatinine, liver function tests, blood sugar.
  
• Infectious disease markers: syphilis; hepatitis B surface antigen; HIV antigen; and antibodies to HIV, hepatitis B core antigen, hepatitis C, HTLV-1, herpes simplex virus, cytomegalovirus (CMV), varicella-zoster virus, and Epstein-Barr virus (EBV).
  
• Pregnancy test when indicated.
  

2.4 Other Practicalities

(a) Liaise with harvest centre and national hub over donor clearance, dates of donor physical examination and harvest, marrow prescription.
(b) Provide harvest centre with standard documentation to accompany marrow (customs forms, copy of letter to airport security, letter stating marrow is non-infectious (to be signed at harvest centre), form detailing marrow collection (Figure 5) (cell count, volume, anticoagulant etc. to be completed at harvest centre).
(c) Advise donor of all practical arrangements:

• Appointment times, admission and discharge times, venues and directions, contact names, contact telephone numbers.
  
• Reimbursement (whether this covers travel expenses, loss of earnings, whether for donor only or also for companion).
  
• Insurance (level of cover, whether it can be raised).
  
• Need for companion (to travel home with).
  
• After-care (follow-up appointments, planned telephone calls, questionnaires to complete, contact names and telephone numbers for donor queries).

3Harvest centre responsibilities

3.1 Donor medical - pre-harvest

(a) Check marrow prescription (Figure 2) (cell count / volume OK for size of donor).
(b) Produce medical report on donor in appropriate time-frame, complete with required laboratory tests (and any additional tests deemed necessary by harvest centre to clear donor), and pronounce donor fit or otherwise.
(c) Ensure availability of autologous unit(s).
(d) Liaise with donor centre/national hub on donor clearance and verification of marrow prescription.

3.2 Donor harvest

(a) Book O/R, anaesthetist, bed for donor.
(b) Harvest marrow, as detailed previously.1
(c) Report quantity of cells harvested and anticoagulant used (Figure 5).

3.3 Confidentiality

*Ensure confidentiality of donor/patient is maintained

3.4 Transferring responsibility for the product (from harvest/donor centre representative to courier)

(a) *Check ID of courier before handing marrow over.
(b) *Supervise courier checking labels on marrow and get signature for hand-over.
(c) Provide courier with customs forms and signed copy of `non-infectious' letter and marrow harvest report (Figure 5), detailing cell count, number of bags, anticoagulant used etc.

* The above items may be covered by either the donor centre coordinator or the harvest centre coordinator.

4 Courier responsibilities

4.1 Personal qualities

The designated courier should be a nurse, medical laboratory technician, doctor, or person of comparable training or comparable level of responsibility. He/she should meet the following requirements:

(a) He/she should not be related to donor or patient.
(b) He/she must be an experienced international traveller.
(c) He/she must have no other obligations until after the marrow is delivered.
(d) He/she must be a major credit card holder with a reasonable limit.

4.2 Prior to picking up the marrow

4.2.1 Confidentiality: The courier should exercise caution in discussing impending travel plans due to the potential of disclosing confidential information.

4.2.2 Travel arrangements

(a) The courier should have arrived in the foreign country by the day prior to the day of harvest.
(b) It is recommended to carry hand luggage only to expedite transit.
(c) Once at the destination hotel in the foreign country, the courier should telephone the contact person to announce safe arrival and check on any last minute changes. The courier should be prepared to visit the contact person if he/she deems it necessary.
(d) The courier should check weather reports at all arrival and departure points and he/she must be prepared to improvise new travel arrangements if necessary. Any change in travel arrangements must be communicated to the transplant centre (if unable to reach the transplant centre, the national registry should be alerted of changes). If necessary, airline supervisors should be informed of the urgency of the marrow delivery.
(e) On the day of harvest, the courier should arrive at the harvest centre at or before the earliest estimated time at which the marrow will be available in order to allow the maximum time to catch the planned flight.

4.3 Picking up the marrow

4.3.1 Transport container and media: The courier must provide the transport box, of a rigid, puncture-proof, insulated nature and any special media, tubes, ice-packs etc. The transport box should not be concealed inside any other item of luggage.

4.3.2 Transferring responsibility for the product (from harvest/donor centre representative to courier):

(a) The courier must present personal identification.
(b) The courier must check the labels on the marrow bags before accepting them from the harvest or donor centre representative - (donor ID, patient ID, anticoagulant), check that extra samples requested by the transplant centre on the marrow prescription (Figure 2) are correct in their entirety, and sign for the marrow and the tubes.
(c) The harvest centre should not be expected to store the marrow on behalf of the courier if the flight is later in the day.

4.4 Returning with the marrow

4.4.1 Documentation: The courier should carry all necessary travel documents (passport, visa, airline ticket, major credit card, international telephone calling card, contact names, addresses, telephone numbers), and additionally, documents confirming the nature of the material, its destination, the marrow harvest report (Figure 5), any necessary customs forms (varying from country to country) and the fact that the product is non-infectious, particularly HIV negative. The marrow bags (or the transport container from which the marrow will not be separated until delivery), should be clearly labelled with the name and address of the transplant physician, the name of the harvesting physician and the identity of the donor's national registry.

4.4.2 Irradiation and security:

(a) The marrow must not be subjected to irradiation in any airport security system. The courier must supervise any hand searching of the marrow and should include a pair of exam gloves in the container to offer for this purpose.
(b) The courier must keep the marrow in hand or in sight at all times and it must travel with the courier in the passenger compartment of the aeroplane and not in the overhead luggage compartment where it may be subject to temperature fluctuations.
(c) The courier should partake of no alcoholic beverages or other intoxicating substances whilst transporting the marrow.

4.4.3 Transport and temperature:

(a) Transport to the airport from the harvest centre is the courier's responsibility.
(b) Transport from the airport to the transplant centre is the courier's responsibility.
(c) Transport and storage directions provided by the transplant centre must be followed. The marrow should generally be carried at room temperature (unless otherwise requested by the transplant centre). Transportation at 4ºC may be optimal for long distances (i.e. greater than 12 hours ex-vivo). The marrow cells must on no account be cooled below 4ºC; neither dry ice nor liquid nitrogen should be used.

4.5 Delivery of the marrow

4.5.1 Transferring responsibility for the product (from courier to transplant centre representative): The courier should deliver the marrow and the marrow harvest report (Figure 5) to a designated person at the transplant centre and receive a signature. (It is the transplant centre's responsibility to notify foreign hub/donor centre of safe arrival of marrow and cell count).

4.5.2 Confidentiality: The courier should observe the rules of patient/donor anonymity. No gifts or correspondence should pass directly between donor and marrow recipient. The courier should take care that no identifying labels on the transport box or marrow bags permit the patient or his/her family to determine where the marrow is from.

Acknowledgements

We thank the Board of the WMDA for critical review of the manuscript.

Reference

1 Goldman JM for the WMDA Executive Committee. A special report: bone marrow transplants using volunteer donors - recommendations and requirements for a standardized practice throughout the world, 1994 update. Blood 1994; 84: 2833-2839.