Blood group incompatibility

in
Peripheral Blood Stem Cell
Transplantation
 Introduction
• Inheritance of HLA antigens –independent of
ABO blood group system

• HLA Matched donor need not be ABO

compatible

• Pluripotent & very early committed stem cells

are devoid of ABH Antigens
• Hence ABO incompatibility is not an obstacle
for successful engraftment
• But …………
• Prevention of immune hemolysis is important
in mismatched transplantations
 Compatibilty rules
• Major Mismatch -recipient has an
antibody against donor

• Minor Mismatch -donor has an antibody

against recipient

• Bidirectional -both
 Major incompatibility
DONOR RECIPIENT

NIL
 Minor incompatibility
DONOR RECIPIENT

NIL

O,B

O,
A

O,A,
B
 Facts
• Antibody titre

• Cross matching

• Transfusion of alternate group

 Incidence
• Incidence of ABO Discordance-30-40%
• Major 20%
• Minor 22-24%
• Bidirectional 1-2%
• Major
1. Immediate hemolysis of RBC infused with the
graft
2. Delayed hemolysis by persistent recipient
isohemagglutinins
3. Delayed erythrocyte engraftment
4. Pure red cell aplasia
 Major
• Immediate hemolysis
• Depends on
– Nature,titre &avidity of recipient antibody
– Volume of red cells in the donor stem cell product
– Antigenic expression on the red cells

• PBSC relatively red cell depleted,yet

hemolysis can occur
 Major
• Delayed hemolysis
– As long as the recipient antibody persists
– Several reports- no immediate but delayed
erythroid engraftment
– More chance with
• High recipient titre
• Delayed erythroid engraftment
– Increased transfusion requirement in major
– Non myeloablative -more delay
– Less commonly delays
• Neutrophil engraftment
• Lymphocyte engraftment
• Platelet engraftment
• PRCA
– Recipient isohemagglutin against donor emerging
RBC
– Intramedullary precursor cell destruction
– BFU E the first stage with ABH Ag
– No evidence of influence on
– myeloid/megakaryocytic engraftment,
– GVHD
– Graft rejection
– Rare
• Strategies to prevent hemolysis
– Removal of RBC from PBSC
– Decrease the concentration of isoagglutinins in
plasma
 DONOR
RECIPIENT Major Recipient No
GROUP&
CROSSMAT
incomp antibody <1/16 proce
CH atibility titre ssing

>1/16

Red cell depletion Plasma exchange

if >20 ml RBCs Plasma adsorption
• Methods of removing red cells
» Centrifugation/sedimentation
» Residual red cells
» Stem cell cell loss

• Goal
• <10 ml red cells
• .5×10 8 MNC/1×10 6 cd34/kg recipient wt
• Need to collect more marrow/process larger
volume of blood
• Inadequate stem cell dose?
 High titer recipient

– RBC reduction
– Plasma exchange/infusion
• Also used when risk of failure(MUD,partial match,aplastic
anemia)
• Infuse donor type plasma
• Non cellular source of ABO soluble substances
• 3-4 days before HCT
• Done after starting of immunosuppression to reduce
rebound increase
• Final titre <1/16
• Continued BD
 Plasma absorption
Recipient titre Number of days
32-128 1d
256-512 2d
1024 3d
>2048 4d

Citrate toxicity FNHTR

TTI TRALI
Platelet Volumeoverloa
d
depletion
 Red cell absorption
• Rarely used technique
– Small aliquot donor type red cell absorption
– 3-4 days prior transplant
– ICU,Potential hemolysis
 Follow up
• Iso agglutinin titres & ABO groups fortnightly
• Titres should ↓
• ↑ titre+ ↑ transfusion reqirement-PRCA
• Once titre <1/4 – see weekly
• Switch to donor type when
• 2 consecutive titres of both IgG and IgM are negative
• Stable graft,producing donor type RBCs, RBC transfusion
independent for at least one month
• Non myeloablative-Gp O till 1 year
 Follow up
• High Ab titre before HCT → ?high probability of
return after transplant
• Weekly titres
• Rising titer heralds delayed onset of
erythropoiesis/hemolysis/both
• Titre >1/16 post transplant →remove Ab by plasma
exchange/absorption
• Trial of EPO-stimulating effect on precursors may
overcome the suppression
 Blood transfusion in Major mismatch

 Before transplant
RBCs,platelets and FFP-recipient's blood type
 After transplant
RBCs only of the recipient's ABO group
Platelets and FFP -the donor's ABO type
 Once blood group switching complete
Donor type blood products
 All cellular products irradiated
 BLOOD GROUP CHOICE IN MAJOR
RECIPIENT DONOR BLOOD PRE POST After
RECIPIENT Ab
PRODUCT TRANSPLA TRANSPLA undetectable
NT NT

O A RBC O O A
PLASMA/PC O A A
O B RBC O O B

PLASMA/PC O B B

A AB RBC A A AB

PLASMA/PC A AB AB

B AB RBC B B AB

PLASMA/PC B AB AB

O AB RBC O O AB

PLASMA/PC O AB AB

AB plasma&O packed washed cells can be used instead of any unavailable group
• Minor
Immediate hemolysis of recipient RBC by donor
derived isohemagglutinin in graft
Delayed hemolysis of recipient RBC by
isohemagglutinin
• Bidirectional
– Both immediate and delayed
 Minor incompatibility
• Immediate –
– Usually not life threatening
– Depends on donor titre

• Delayed hemolysis
– Can be abrupt,fatal ,multiorgan failure
– 5-17 days post PBSCT
– Rh kidd Le also

• Evidence of hemolysis with DCT +

• Ab of donor specificity eluted from recipient
• Clinically significant hemolysis 15-71%
 Minor
• More risk of clinically significant hemlysis
– In PBSCT -Tenfold more lymphoid cells
– T cell depleted BMT
– CSP prophylaxis without methotrexate
• G CSF-T lymphocyte production of cytokines which promote
antibody formation by B lymphocytes

• Rapid severe hemolysis

• Coincides with early complete donor type
engraftment/appearance of a/c GVHD
• Early onset of hyperbilirubinemia-could be a
clue but non specific
• Massive delayed hemolysis-CSP alone
• Bystander hemolysis
– Transfused O RBCs hemolysed
• In minor ,pretransplant titers doesn’t predict
incidence/severity of delayed hemolysis

• Approaches
Removal of plasma from donor stem cell product
• If titre >128; plasma removal by centrifugation
• No substantial loss of stem cell
Pre transplant dilution of recipient’s RBC with Gp O
RBCs(Prophylactic transfusion/exchange of RBC)
o RBC exchange More successful in donor with high titres
 Minor
>256; plasma
IgG and IgM titre reduction if total
of donor component
volume>200ml
CSP
prophylaxis
without MTx-
Prohylactic gp
O RBC
transfusion
irrespective of
<256(128 in
titre
children) no
processing
• Chance of hemolysis
• Coinciding with engraftment
– DCT
– Antibody screening
– Every 2 days during first 3 post transplant weeks
• If DCT +ve elute and confirm donor specificity
– Reticulocyte, peripheral smear
• If hemolysis suspected
– LDH,Bilirubin,Haptoglobin daily till patients
hematocrit stable
 Minor
• Before transplant
• PRC &Plasma & Platelets- Recipients type
• O washed cells can be used for dilution effect if
needed
• After transplant
• RBC -donor's ABO group
• Plasma and platelets -recipients
• Once blood group switching complete
• Donor type blood products
 BLOOD GROUP CHOICE IN MINOR

RECIPIENT DONOR BLOOD PRE POST After

RECIPIENT
PRODUCT TRANSPLANT TRANSPL RBC
ANT undetectable

A O RBC A O O
PLASMA/PC A A O
B O RBC B O O

PLASMA/PC B B O

AB O RBC AB O O

PLASMA/PC AB AB O

AB A RBC AB A A

PLASMA/PC AB AB A

AB B RBC AB B B

PLASMA/PC AB AB B

AB plasma&O packed washed cells can be used instead of any unavailable group
 Bidirectional
• Do recipient & donor antibody titre
– Red cell& plasma depletion
– Patient’s RBC diluted to Gp O RBCs
– If recipient antibody titre>1/256 plasma exchange
– Gp O Red cell products and Gp AB plasma for
post transplant support
 Bidirectional
• Gp O RBC and Gp AB plasma
and platelets for pre and post transplant
support
• Once recipients original Ab
undetectable,donor redcells,plasma,platelets
 Rh incompatibility
• Major mismatch
– Recipient Rh D negative& sensitised
– Donor rh D positive
– Antibody titre
– Red cell removal /±plasma exchange/absorption
• Minor mismatch
– 6-15% hemolysis
– Recipient negative donor sensitised +ve
– Prophylxis with Rh negative blood
• Transfusion
• Same in both major/minor
– Post transplant Rh negative PRC,Rh
positive/negative plasma
THANK YOU