JPAC Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee

22.11: Testing of haemopoietic progenitor cell donors and components including therapeutic cells

22.11.1: Infectious disease marker testing

This must be done in accordance with the requirements of the EU Directives on Tissues and Cells, SaBTO, FACT-JACIE and NetCord-FACT.

The minimum current requirements include testing for HIV, HTLV I/II, HBV, HCV and syphilis. Additional testing may be required in some cases, e.g. for malaria and toxoplasmosis. Table 22.1 indicates the requirements for the timing of testing for each type of HPC, while Chapter 9 contains further information on microbiology testing procedures.

 

Table 22.1 Requirements for the timing of testing

Test Allo HPC-A/
HPC-M/TC
Auto HPC-A/
HPC-M
HPC-C donor mother HPC-C

ABO + RhD

Test at each donation

Test at first donation

 

Day 0 to Day +7

anti-HIV 1/2 antibody

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

Prior to release

anti-HCV antibody

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

Prior to release

anti-HTLV I/II/(pooled) antibody

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

Prior to release

HCV RNA (pooled)

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

Prior to release

HBsAg

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

Prior to release

anti-HBc antibody

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

Prior to release

CMV

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

Prior to release

Pregnancy test

–7 days preconditioning

 

 

 

Malaria

Where clinical indication

Where clinical indication

Where clinical indication. All mothers where there is risk

 

Haemoglobinopathy, i.e. sickle cell

Where clinical indication

Where clinical indication

 

Prior to release

Syphilis screen*

Day –30 to Day 0

Day –30 to Day 0

Day –7 to Day +7

 

Bacteriology testing

If manipulation

If manipulation

 

On final product

FBC

Before each apheresis procedure

Before each apheresis procedure

 

Pre and post process

* Confirmatory tests should be performed if screen positive

Additional tests must be undertaken for quarantined HPC-C products where a Day 180 repeat test has not been performed on the mother. The following tests should be performed on the mother’s initial sample to permit release:

  • HIV PCR pooled/single
     
  • HCV PCR pooled/single
     
  • HBV PCR single

Mechanisms should be in place to ensure that archived material/samples can be re-tested at the time of issue of donation for all current markers of infection including the latest generation of assays.

22.11.2: HLA typing

  • At initial registration: HLA-A, -B, -DR type by a Clinical Pathology Accreditation (CPA) and European Federation for Immunogenetics (EFI) accredited laboratory. As a minimum these antigens should be defined at low/medium resolution level using DNA techniques.
     
  • Confirmatory typing: Must be performed on a sample drawn independently of that used for initial registration. HLA-A, -B, -C, -DRB3, -DRB4, -DRB5 and -DQB1 types should be defined, at a minimum, to medium resolution using DNA techniques. HLA-DRB1 should be defined to the allele level by DNA techniques. High/allele resolution typing for HLA-A, -B, -C, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 can also be performed as required by the transplant protocol.

For cord blood donations it is recommended that a maternal sample is HLA typed to confirm identity. High-resolution typing of cord blood units shall take place when requested by a transplant centre. In cord blood banking, prior to the release of a cord blood unit for transplantation a sample obtained from a contiguous segment of the cryopreserved cord blood unit must be tested to verify HLA type or short tandem repeat (STR) can be performed according to NetCord-FACT Standards.

22.11.3: ABO and RhD typing

For allogeneic donors of HPC-A and HPC-M, ABO and RhD typing must be performed on samples taken from the donor or cell therapy component at the time of each collection. For autologous donors of HPC-A and HPC-M, ABO and RhD typing must be performed on samples taken from the donor or cell therapy component at the time of first collection. For HPC-C the ABO and RhD type of each donation shall be determined.

22.11.4: Clonogenic assays

Clonogenic assays (e.g. CFU-GM) may be undertaken as part of a quality programme or when specifically indicated or requested by the transplant physician. Consideration should be given to performing surrogate tests for viability prior to conditioning on a representative archive sample of any cryopreserved HPC components. For cord blood units CD34+ cells should be enumerated according to NetCord-FACT Standards and progenitor cell assays should be assessed on a thawed sample before release of the unit for transplant.

22.11.5: Sterility

Bacteriological and fungal screening employing aerobic and anaerobic conditions must be performed on the final HPC component after processing and before cryopreservation, unless validation studies demonstrate that bacteriological screening of waste processing material, such as plasma or erythrocytes, are equivalent to screening of the final product. All positive cultures should be subsequently identified and antibiotic sensitivities performed if the material is to be put to clinical use.

22.11.6: Test samples

Archival samples must be stored for reference and any future testing that may be required as described in the EU Directives on Tissues and Cells, FACT-JACIE Standards and NetCord-FACT Standards. Documentation must be kept to ensure security and accurate retrieval of the stored samples when required. Storage conditions must:

  • maintain cell viability (below –150°C)
  • be suitable to obtain material for the preparation of 50 mg DNA.