Canterbury DHB

Cord Blood Transplantation (CBT)

Historical Aspects

The potential value of cord blood transplantation has been known since the early 1970s. Murine studies indicated that umbilical cord blood contained high numbers of primitive haemopoietic cells and that such cells could rescue lethally irradiated syngeneic mice. Subsequent studies confirmed that haemopoietic progenitors exist in large numbers in human cord blood. The lack of a suitable in vitro assay for pluripotential haemopoietic stem cells (PHSC) delayed the development of human CBT.

The first human CBT was performed by Eliane Gluckman on a 5 year old child with Fanconi’s anaemia in 1988 using an HLA-identical related sibling cord blood donation. The successful outcome of this procedure stimulated others to perform such transplants which were carried out on children with inherited conditions/aplasia/ malignancy using sibling related donations which were predominantly HLA identical. This led to the establishment of the International Cord Blood Transplant Registry.

For a review of Cord Blood Transplants (CBT) and the advantages and disadvantages of CBT compared to standard allograft SCT matched sib or MUD see Tse and Laughlin, ASH EPB, 2005.

Indications for Cord Blood Transplantation

Related

This situation will arise rarely, and the indication for CBT will need to be considered on an individual basis.

Unrelated

• Single Cord SCT is usually only considered for patients who weigh <30 kg and who have a minimum of >2.0 X 10⁷ matched cells/kg. However double CBTs are increasingly being used and allow CBT to be given to larger individuals. Each potential CBT candidate will be considered on an individual basis.
• In practice this means that unrelated CBT is usually considered for children with malignancy, inborn errors, and immune deficiencies. See Eurocord Guidelines.
• The recipients preferably should be matched for 5/6 or 6/6 HLA antigens (eg A, B, DR B1; be a full match or 1 antigen mismatch, be less than 11 years and be CMV negative).
• A single class I mismatch is preferable to a single class II mismatch. If one HLA class I mismatch is present it is preferable for this to be in HLA A vs B locus. 3 mismatches are unacceptable.
• 2 mismatches yield poor results. Under these circumstances these mismatches should either be in class I or II but not mixed class I and II.
• The cord blood should contain as many cells as possible (target 4.6 X 10⁷ nucleated cells/kg pre thaw; 3.7 x 10⁷ cells post thaw).

Fuller Information about Cord Blood Transplants

See:

• International Cord Blood Banks.
  • Bone Marrow Donors Worldwide (BMDW, www.bmdw.org) maintains a database of the number of cord blood units stored worldwide by BMDW affiliated registries.
  • As of June 2010, BMDW reported a total of 426,501 cord blood units stored at 42 cord blood banks in 28 countries. The vast majority of the units will have been DR typed at the molecular level. In contrast there are approximately 14 million bone marrow donors on bone marrow donor registries and, depending on the registry, 20-80% have had some degree of DR typing (?what percentage molecular).
  • Experience from the New York Cord Blood Bank has indicated a 6.8% chance of delivering a 6/6-matched donor and an additional 53% chance of 5/6-matched donor. A proposal has been put to the Ministry of Health for the establishment of a New Zealand Cord Blood Bank to target Maori/Pacific Island population groups.
  • Netcord has been established as a non-profit organisation dedicated to establishing criteria for qualification and accreditation of cord blood banks and to help facilitate donor searches. In collaboration with FACT they have produced an updated version of their standards for cord blood banking.
  • The Eurocord Cord Blood Transplant Group has been established to analyse data and outcomes of CBT and to help facilitate standard/research protocols for CBT.

• Cord Blood SCT Search Procedure.

  A request for cord blood search is made through the NZBMDR following high-resolution class II typing of the recipient, and approval of the SCT Committee. It would be appropriate to search simultaneously the cord blood banks and bone marrow donor registries as outlined below.

  

  Depending on these results, the SCT Committee decides whether to proceed with an unrelated SCT, either adult donor or cord.

  Notes:

  • The final decision, on donor selection and procedure, must take into account the degree of HLA identity, the availability of the donor, the speed of the search, the urgency of the transplant, the number of cells present in the cord blood and in the case of unrelated bone marrow donor transplants, the donor age, sex, number of pregnancies and CMV status.
  • Following a request for a cord blood search the transplant centre will receive brief summary data on cord blood units such as HLA type but further information can be requested such as cell dose.
  • If appropriate the transplant centre may then request confirmatory typing of selected cord blood units. A central laboratory approved by Netcord or NMDP often does this and the transplant centre is usually asked to submit samples for patient confirmatory typing to the same laboratory. If available, material from the cord blood bank may also be sent to the transplant centres own laboratory for confirmatory typing.
  • These results are sent back to the transplant centre that may then select a cord blood unit for transplant. The cord blood bank then makes arrangements to ship the frozen cord blood unit to the transplant centre to arrive well before the start of the conditioning treatment of the patient.

  Approval for payment of the cord blood unit (usually US$20-25,000) will need to be made along with expenses involved with shipping/insurance. Policies of cord blood banks differ with regard to shipping instructions eg as to whether a courier should travel with the cord blood unit or should the cord blood bank/transplant centre provide a courier/dry shipper.

  Note: In order to assist the evaluation of CBT, procedures will be carried out according to current Eurocord guidelines and the results reported to the Eurocord Cord Blood Transplant Group.

• Procedure for the Harvest of related cord blood.

Topic Code: 8912