peripheral stem cell transplant with blood group incompatibility-how to manage

8/6/2019 Peripheral Stem Cell Transplant With Blood Group Incompatibility-how to Manage

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Blood group incompatibility

inPeripheral Blood Stem Cell

Transplantation


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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 ofABH Antigens


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Hence ABO incompatibility is not an obstacle

for successful engraftment

But Prevention of immune hemolysis is important

in mismatched transplantations


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Major incompatibilityRECIPIENTDONOR

NIL


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Minor incompatibility

NIL

O,

A

O,B

O,A,

B

DONOR RECIPIENT


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Facts

Antibody titre

Cross matching

Transfusion of alternate group


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Incidence

Incidence of ABO Discordance-30-40%

Major 20%

Minor 22-24% Bidirectional 1-2%


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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


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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 canoccur


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Major

Delayed hemolysis

As long as the recipient antibody persists

Several reports- no immediate but delayed

erythroid engraftment More chance with

High recipient titre


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Delayed erythroid engraftment

Increased transfusion requirement in major

Non myeloablative -more delay Less commonly delays

Neutrophil engraftment

Lymphocyte engraftment

Platelet engraftment


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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


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Strategies to prevent hemolysis

Removal of RBC from PBSC

D

ecrease the concentration of isoagglutinins in plasma


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DONOR

RECIPIENT

GROUP&

CROSSMAT

CH

Major

incompatibility

Recipient

antibodytitre

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Red cell depletion

if >20 ml RBCsPlasma exchange

Plasma adsorption


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Methods of removing red cells Centrifugation/sedimentation

Residual red cells

Stem cell cell loss

Goal


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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 reducerebound increase

Final titre


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Plasma absorption

Recipienttitre Numberofdays

32-128 1d

256-512 2d

1024 3d

>2048 4d

Citrate toxicity

TTIPlateletdepletion

FNHTRTRALIVolumeoverload


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Red cell absorption

Rarely used technique

Small aliquot donor type red cell absorption

3-4 days prior transplantICU,Potential hemolysis


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Follow up

Iso agglutinin titres & ABO groups fortnightly

Titres should

titre+ transfusion reqirement-PRCA

Once titre


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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


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Blood transfusion in Major mismatch

Before transplant

RBCs,platelets and FFP-recipient's blood type

After transplantRBCs 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


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BLOOD GROUP CHOICE IN MAJORRECIPIENT DONOR BLOOD

PRODUCT

PRE

TRANSPLA

NT

POST

TRANSPLA

NT

After

RECIPIENT Ab

undetectable

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


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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 promoteantibody formation by B lymphocytes

Rapid severe hemolysis

Coincides with early complete donor type

engraftment/appearance of a/c GVHD


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Early onset of hyperbilirubinemia-could be a cluebut non specific

M

assive delayed hemolysis-CSP alone Bystander hemolysis

Transfused O RBCs hemolysed


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In minor ,pretransplant titers doesnt predict

incidence/severity of delayed hemolysis

ApproachesRemoval of plasma from donor stem cell product

If titre >128; plasma removal by centrifugation

No substantial loss of stem cell

Pre transplant dilution of recipients RBC with Gp ORBCs(Prophylactic transfusion/exchange of RBC)

o RBC exchange More successful in donor with high titres


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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


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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


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BLOOD GROUP CHOICE IN MINOR

RECIPIENT DONOR BLOOD

PRODUCT

PRE

TRANSPLANT

POST

TRANSPL

ANT

After

RECIPIENT

RBC

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


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Bidirectional

Do recipient & donor antibody titre

Red cell& plasma depletion

Patients 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


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Bidirectional

Gp O RBC and Gp AB plasma andplatelets for pre and post transplant support

Once recipients original Ab undetectable,donorredcells,plasma,platelets


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Rh incompatibility

Major mismatch

Recipient Rh D negative& sensitised

Donor rh D positive

Antibody titre Red cell removal /plasma exchange/absorption


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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,Rhpositive/negativeplasma


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THANK YOU

peripheral stem cell transplant with blood group incompatibility-how to manage

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