ABO / Rh Incompatible Stem Cell Transplant (NHSBT 2011)

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

 

Intro

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

o   Acute haemolysis at time of stem cell infusion

o   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

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

o   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

o   Red Cells: Recipient ABO group, or group O

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

o   Red Cells: Donor ABO group

o   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

o   Red Cells: Group O

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:

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

o   The DAT is negative using polyspecific AHG

o   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

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

-        Minor Incompatibility

o   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 à 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?

o   Error

o   Super emergency cases

o   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