The following guidance has been created to reduce errors and optimise safety of transfusions in autologous and allogeneic haemopoietic stem cell transplant (HSCT) recipients and should be used by the transplant centre team as part of every transplant recipient’s journey. The blood group changes are only applicable to allogeneic stem cell transplants where ABO and/or D groups are different. This document should be used in conjunction with local policies relating to provision of blood components for HSCT.

It is recommended that a checklist must be completed by the transplant centre team as part of every transplant recipients’ journey to ensure safe transfusion requirements are met. (See Appendix 1 for example)

The blood group changes are only applicable to allogeneic stem cell transplants where ABO and/or D groups are different.

Around 25-50% of the HLA matched allogeneic transplants are ABO incompatible. ABO matching is not required for a successful HSCT.

Risks of incompatible transfusion

Acute haemolysis at time of stem cell infusion or delayed haemolysis due to production of antibodies by residual host/passenger lymphocytes may occur.

Red cell aplasia has also been described in cases of major ABO incompatibility. The risk for any of these complications depends on the volume of red cells infused and the titre of antibody present.

Over weeks to months, the recipient develops donor haemopoiesis and immune function, but this depends on several factors.

Major ABO incompatibility occurs with the presence of anti-A, anti-B and anti-A,B antibodies in the recipients plasma incompatible with donor red cells.

Minor ABO Incompatibility occurs when anti-A, anti-B or anti–A,B antibodies are present in the donor’s plasma reactive with the recipient’s red cells.

Major plus Minor (bidirectional) ABO Incompatibility is present when both the donor and recipient’s plasma have anti-A, anti-B or anti-A, B antibodies reactive with recipient and donor cells respectively

Table 1: Compatible, major, minor, and bidirectional (both) incompatible HSCT

Pre-transplant (Phase I – period from diagnosis to transplant): Recipient-group red cells and platelets should be given.

Post-transplant immediate phase (Phase II- period from transplant to RBC engraftment): The guidance below applies to the immediate post-transplant period until all the following criteria are fulfilled:

1. ABO antibodies to the donor ABO group are undetectable in the ‘standard’ reverse group and by indirect antiglobulin test using A1 and/or B cells (major ABO incompatibility only).

2. The direct antiglobulin test (DAT) is negative.

3. Conversion to donor group is complete, with no mixed field seen using the patient’s cells in standard serological tests with anti-A or anti-B (in practice this can only be demonstrated if there have been no red cell transfusions in the last 3 months).

Major ABO incompatibility:

• For red cells: red cells of recipient’s ABO group or group O should be given

• For platelets and Fresh Frozen Plasma (FFP): give platelets and plasma of donor ABO group. Where donor is group AB use group A high-titre negative platelets. When the recipient is group A, and group B high-titre negative platelets when the recipient is group B (see Table 2 below)

Minor ABO incompatibility:

• For red cells: red cells of donor ABO group should be given

• For platelets and FFP: give platelets and plasma of recipient ABO group. Where recipient is group AB, group A high titre-negative platelets may be used when the donor is group A, and group B platelets when the donor is group B (see Table 2 below).

Major plus minor (“bidirectional”) ABO incompatibility:

• For red cells: red cells of group O should be given

• For platelets and FFP: give group AB plasma and recipient group platelets

Post-transplant after engraftment (Phase III, when all the above criteria are met):

Post engraftment, when ABO antibodies to the donor ABO type are undetectable and the DAT is negative, the donor group may be selected.

However, it should be noted that it is increasingly common for multiple cord donations to be used and that each donor cord may be of a different ABO and/or D group. Post‐ engraftment transfusion management should be decided on a case‐by‐case basis and will depend on which cord engrafts, in accordance with British Society for Haematology (BSH) guidelines relating to pre‐transfusion compatibility procedures in blood transfusion laboratories

(https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-3148.2012.01199.x).

In case of graft rejection, the selected red cells should remain compatible with both the patient and donor until complete reversion to the original recipient ABO and D type. Then provision of all components must revert to recipient-type red cells and platelets

Table 2: Selection of Appropriate blood groups for recipients of ABO mismatched stem Cell transplant

Incompatibility between donor and recipient for the D red cell antigen occurs commonly in the setting of allogeneic HSCT.

• Major Rh incompatibility exists where a donor is D-positive and a recipient D-negative. Minor Rh incompatibility occurs where a donor is D-negative, and the recipient is D- positive.

• In cases of minor Rh incompatibility delayed haemolysis can occur due to donor lymphocyte-derived anti-D.

The risk is higher if the donor has been previously sensitised to the D antigen and in recipients of non-D selected peripheral blood stem cells

• Pre-transplant:

recipient-type red cells and platelets should be given

• Post-transplant:

• HSCT recipients should receive D-negative red cells and platelets except when both the HSC donor and recipient are D-positive

• Major RhD incompatibility: D-negative blood components to be given until D-positive red cells are detected. Thereafter can receive D-positive components

• Minor RhD incompatibility: D-negative blood components should be given indefinitely.

Please note that BSH guidelines (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-3148.2012.01199.x) state that when either the recipient or donor is D-negative, D- negative red cells should be selected. Refer to local policies when making these decisions and consult local transfusion experts.

Immune haemolysis following HSCT caused by alloantibodies directed against the Kidd, MNSs and Kell antigen systems have all been described and the haemolysis can be severe if several alloantibodies are simultaneously involved.

Donors should be phenotyped for the relevant blood group antigen and the donor marrow should be red cell depleted where indicated. If advice is required, discuss with a transplant or red cell immunohaematology consultant.

(from the 2020 BSH guidelines on the use of irradiated blood components):

• All recipients (adult and paediatric) of allogeneic HSCT should receive irradiated blood components from the time of initiation of conditioning chemo/radiotherapy.

• The recommendation applies for all conditions where HSCT is indicated regardless of the underlying diagnosis

• Irradiated components should be continued until all the following criteria are met:

1. ≥6 months have elapsed since the transplant date

2. The lymphocyte count is >1·0 × 109 /L

3. The patient is free of active chronic Graft versus Host Disease (GvHD)

4. The patient is off all immunosuppression

• If chronic GvHD is present or continued immunosuppressive treatment is required, irradiated blood components should be given indefinitely.

• Treatment with irradiated blood components should continue indefinitely if this is required based on transplant conditioning, underlying disease or previous treatment, e.g. previous diagnosis of Hodgkin’s lymphoma or previous purine analogue treatment

• Allogeneic cellular blood components transfused to bone marrow and peripheral blood stem cell donors of all ages within 7 days prior to or during the harvest should also be irradiated Autologous stem cell transplantation (ASCT):

• Patients (adult and paediatric) undergoing bone marrow or peripheral blood stem cell collections for future autologous re‐infusion should receive irradiated cellular blood components for 7 days prior to and during the bone marrow/stem cell harvest to prevent the collection of viable allogeneic T lymphocytes, which can potentially withstand cryopreservation.

• All patients undergoing ASCT irrespective of underlying diagnosis or indication for this treatment should receive irradiated cellular blood components from initiation of conditioning chemo/radiotherapy until 3 months post‐transplant (6 months if total body irradiation was used in conditioning) unless conditioning, disease or previous treatment determine indefinite duration, for e.g. previous diagnosis of Hodgkin’s lymphoma or previous purine analogue treatment

• All patients in whom HSCT is considered as a potential treatment option must have baseline CMV testing performed as blood transfusions can result in false positive tests due to passive transfer of antibodies.

• CMV-negative components are not required irrespective of serological status of donor and recipient for HSCT. Leucodepleted blood components suffice for adults and children post haemopoietic stem cell transplantation for all patient groups including CMV-seronegative donor/seronegative recipients. All blood components issued in UK are leucodepleted.

• Patients requiring transfusions who may require a transplant in the future may also safely be transfused with leucodepleted products (e.g., seronegative leukaemia or thalassaemia patients)

• CMV PCR monitoring should be considered for all patients (even CMV negative/negative patients) to allow early detection of any possible CMV infection (whether transfusion transmitted or otherwise acquired)

Topic: Safe transfusion in HSCT recipients

Sources checked: NICE, Pubmed, Cinhal, Cochrane, UpToDate, Trip pro and BMJ Best Practice
Search terms: Autologous and Allogeneic Haemopoetic Stem Cell Transplantation, Haemopoetic Stem Cell Transplantation, Stem Cell Transplantation.

Limits: Published since 10 years

Please contact for assistance obtaining full-text copies or for further searches.

Guidelines

Cutler, C. (2022) ‘Long-term care of the adult hematopoietic cell transplantation survivor’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: Long-term care of the adult hematopoietic cell transplantation survivor (Accessed: 19 September 2023).

[NB. This is a time-limited URL to the full-text. If adding this reference to a guideline, use https://www.uptodate.com/] 

Negrin, R. S. (2022) ‘Early complications of hematopoietic cell transplantation’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: Early complications of hematopoietic cell transplantation (Accessed: 19 September 2023).

[NB. This is a time-limited URL to the full-text. If adding this reference to a guideline, use https://www.uptodate.com/] 

Negrin, R. S. (2022) ‘Preparative regimens for hematopoietic cell transplantation’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: Preparative regimens for hematopoietic cell transplantation (Accessed: 19 September 2023).

[NB. This is a time-limited URL to the full-text. If adding this reference to a guideline, use https://www.uptodate.com/] 

Raaijmakers, M. HGP. (2023) ‘Overview of stem cells’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: Overview of stem cells (Accessed: 19 September 2023).

[NB. This is a time-limited URL to the full-text. If adding this reference to a guideline, use https://www.uptodate.com/] 

Shane, E. (2023) ‘Prevention and treatment of osteoporosis after solid organ or stem cell transplantation’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: Prevention and treatment of osteoporosis after solid organ or stem cell transplantation (Accessed: 19 September 2023).

[NB. This is a time-limited URL to the full-text. If adding this reference to a guideline, use https://www.uptodate.com/] 

Wingard, J. R. (2022) ‘Prevention of infections in hematopoietic cell transplant recipients’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: Prevention of infections in hematopoietic cell transplant recipients (Accessed: 19 September 2023).

[NB. This is a time-limited URL to the full-text. If adding this reference to a guideline, use https://www.uptodate.com/] 

National Institute for Health and Care Excellence [NICE] (2022) COVID-19 rapid guideline: haematopoietic stem cell transplantation. NG164. Available at: https: www.nice.org.uk="" guidance="" ng164="" (Accessed: 20 September 2023).

National Institute for Health and Care Excellence [NICE] (2021) Lenalidomide maintenance treatment after an autologous stem cell transplant for newly diagnosed multiple myeloma. TA680. Available at: https: www.nice.org.uk="" guidance="" ta680="" (Accessed: 20 September 2023).

National Institute for Health and Care Excellence [NICE] (2022) Melphalan for haematological diseases before allogeneic haematopoietic stem cell transplant (terminated appraisal). TA822. Available at: https: www.nice.org.uk="" guidance="" ta822="" (Accessed: 20 September 2023).

Other studies

Miller, et al. (2023) ‘Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients: Prepared on behalf of the British society of blood and marrow transplantation and cellular therapy (BSBMTCT), the Children's cancer and Leukaemia Group (CCLG), and British Infection Association (BIA)’, Journal of Infection, 86(1), pp. 1-8. Available at: https: doi.org="" 10.1016="" j.jinf.2022.11.005=""

British Committee for Standards in Haematology, et al. (2012) 'Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories', Transfusion Medicine, 23(1), pp. 3-35. Available at: https://doi.org/10.1111/j.1365-3148.2012.01199.x (Accessed: 20 September 2023).

Carreras, E. et al. (2019) The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. Cham: Springer, 702 p. Available at:https://www.ebmt.org/sites/default/files/2019-01/2019_Book_TheEBMTHandbook.pdf (Accessed: 20 September 2023).

British Committee for Standards in Haematology, et al. (2012) 'Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories', Transfusion Medicine, 23(1), pp. 3-35. Available at: https://doi.org/10.1111/j.1365-3148.2012.01199.x (Accessed: 20 September 2023).

This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date. This guideline is for use in Frimley Health Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

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