ABO / Rh Incompatible Stem Cell Transplant (NHSBT 2011)

Intro

30,000 HSCT performed in Europe in 2012

30-50% are ABO-mismatched

BMT Journal 2015 – UK study - ABO mismatch does not affect OS in RIC HSCT

 

background

ABO incompatibility does not affect graft rejection or GVHD since ABO antigens are not expressed on primitive stem cells --> large numbers of ABO incompatible transplants because HLA type trumps ABO in donor selection.

 

Maximum haemolysis usually occurs 9-16 days post-transplant, occasionally severe and intravascular.

More common with PBSC than bone marrow due to a higher number of lymphocytes being infused.

Very rare if graft has been T-cell depleted with alemtuzumab, or undergone CD34+ cell selection.

 

Complications of ABO incompat HSCT

 

Pure red cell aplasia

Haemolysis – 4-5% of all HSCT. Risk increased by unrelated donors and chronic GVHD.

Passenger lymphocytes – unexpected antibodies produced by lymphocytes transplanted into patient. Usually occurs 7-10 days post-transplant. Self-limiting until lymphocytes die. DAT+. IgG usually but can be IgM.

 

Definitions

 

Major ABO incompatibility

Presence in the recipient’s plasma of Anti-A, Anti-B or Anti-A,B antibodies incompatible with donor red cells, e.g. Group A donor, Group O recipient

Potential Risks

  • Acute haemolysis at time of stem cell infusion

  • Delayed haemolysis due to production of antibodies by residual host lymphocytes

 

Minor ABO incompatibility

Presence in the donor’s serum of Anti-A, Anti-B or Anti-A,B antibodies reactive with the recipient’s red cells, e.g. Group O donor, Group A recipient

Potential Risks

  • Acute haemolysis at time of stem cell infusion due to Anti-A or Anti-B in the donor plasma product

  • Delayed haemolysis of recipient cells due to passenger lymphocyte syndrome

 

Bidirectional

The presence in both the donor and the recipient’s plasma of anti-A, anti-B or anti-A.B antibodies reactive with the recipient and donor cells respectively, e.g. Group A donor, Group B recipient

Risks as for both of the above

 

Investigations

 

Pre-transplant

  • ABO + D group and antibody screen

  • Anti-A and Anti-B titres by IAT

  • DAT

Post-transplant

  • Monitor for haemolysis – immediate and delayed

 

Choice of ABO group for transfusion

 

Pre-Transplant

Recipient type red cells and platelets should be given

 

Post-Transplant

Pre-engraftment

  • Major Incompatibility

    • Red Cells: Recipient ABO group, or group O

    • Plts/FFP: If the donor is group AB, use group A high titre negative units if the recipient is group A and use group B high titre negative units if the recipient is group B.

  • Minor Incompatibility

    • Red Cells: Donor ABO group

    • Plt/FFP: If the recipient is group AB, use group A high titre negative units if the donor is group A and use group B high titre negative units if the donor is group B

  • Bidirectional

    • Red Cells: Group O

    • Plt/FFP: AB plasma and recipient group platelets

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 Post-engraftment

This is defined as when all of the following criteria are met:

  • ABO antibodies to the donor group are undetectable in the reverse grouping and by IAT (applies to major incompatibility only)

  • The DAT is negative using polyspecific AHG

  • Conversion to donor group is complete, with no mixed field reactions (in practice this is only demonstrable once there have been no red cell transfusions for three months)

 

Graft Rejection

Following graft rejection use recipient group red cells and platelets.

 

Choice of Rh D group for transfusion

 

Pre-Transplant

  • Recipient type red cells and platelets

Post-Transplant

  • Major Incompatibility

    • RhD negative components until RhD positive cells are detected. Thereafter give RhD positive.

  • Minor Incompatibility

    • RhD negative components indefinitely.

 

N.B. Some hospitals use group O red cells indefinitely for all patients

 

Solid Organ Transplant

 

Renal Transplant

Historically ABO compatible only as kidneys express A&B antigens —> failed engraftment

Now using immunoabsorption to remove IgG Anti-A and Anti-B (live donations only)

Accommodation = process by which graft kidney persists post-transplant even once recipients anti-A or anti-B titre rises again

 

Liver Transplant

Need a lot of blood, already been sick for some time, may have had previous transplants

Often already have antibodies

Blood bank attends the liver transplant MDT to plan product supply

Beyond 10 units can drop antibody / ABO matching due to dilution and depletion of patient’s own plasma

When to ABO incompat liver transplants occur?

  • Error

  • Super emergency cases

  • Paediatrics

 

Rh D+ organ --> Rh D- recipient

1500 units Anti-D

Flow cytometry 48 hours later

 

Circulatory Death Donors

Can use normothermic ECMO with donor blood and blood products matched to donor

Provides regional circulation to the organ due to be harvested

 

Ex-Vivo Normothermic perfusion (EVNP)

Prior to transplant and during transport of organ around the country

Designed to improve the quality of marginal organs and so increase the donor pool

Group O used to perfuse the organ