ABO INCOMPATIBLE STEM

CELL TRANSPLANT:
LABORATORY SIDE

Kenneth Amenyah
Operations Manager
Blood Transfusion Laboratory (Viapath)
King’s College Hospital NHS Trust
February 2017
 Aims & Objectives
• Introduction and an overview of ABO incompatibility in
haematopoietic stem cell transplant (HSCT)
• Outline the different phases of transfusion support & complications
in haematopoietic stem cell transplant (HSCT)
• Describe challenges associated with ABO incompatible
haematopoietic stem cell transplant

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 Introduction
• The human leukocyte antigen (HLA) and the ABO blood group system allows for
HLA-matched haematopoietic progenitor cell transplantation to occur for donors
who are not matched for ABO blood groups.
• Haematopoietic stem cell transplantation is used to treat variety of haematological
and congenital diseases. Rare but predictable complications may arise when the
transplanted stem cells are incompatible with the native ABO type of the patient.
• Lately, there has been an increased use of hematopoietic progenitor cell
transplantation which is having implications and consequences for Blood
Transfusion Laboratory (BTL)

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 HLA and ABO Antigens
• HLA remains the single most important
factor to consider in selecting donor.
• HLA and ABO are inherited separately.
• HLA found on Chromosome 6 (6p21.3)
contains 200 genes and expressed on WBC.
• ABO found on Chromosome 9 expressed on
RBC.
• HLA strongest predictor for occurrence of
severe GVHD.

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 Overview of ABO incompatibility in HSCT

ABO mismatch in HSCT

• Has no effect on engraftment due to absence of ABO antigens on stem
cells
• The lack of the ABO antigens allow for homing and engraftment of stem
cells regardless of ABO incompatibility
• Does not affect neutrophil, platelet engraftment, graft failure or rejection.

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 Overview of ABO incompatibility in HSCT
TYPES OF HSCT
By donor:
• autologous
• allogenic
related vs. unrelated
matched vs mismatched
By source of hematopoietic stem cells:
• bone marrow (HPC-M)
• peripheral blood stem cells (HPC-A)
• cord blood (HPC-C)
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 Red blood cell classification of allogenic
incompatibility in HSCT
• MAJOR
• recipient has ABO antibodies directed against donor RBC

• MINOR
• donor has ABO antibodies directed against recipient RBC

• BIDIRECTIONAL: major and minor ABO incompatibility:

• recipient has ABO antibodies directed against donor red cells
• donor has ABO antibodies directed against recipient red cells

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 Classification of HSCT by ABO blood group
Donor and Recipient
Recipient Donor ABO group
ABO Group

O A B AB

O Identical Major Major Major

A Minor Identical Bidirectional Major

B Minor Bidirectional Identical Major

AB Minor Minor Minor Identical

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Transfusion support for HSCT recipients
Major ABO incompatible
Recipient Donor Red cells Platelets/FFP

O A O A, AB

O B O B, AB

A AB A AB

B AB B AB

O AB O AB
Transfusion support for HSCT recipients
Minor ABO incompatible
Recipient Donor Red Cells Platelets/FFP

A O O A, AB

B O O B, AB

AB O O AB

AB A A AB

AB B B AB
Transfusion support for HSCT recipients
Bidirectional ABO incompatible
Recipient Donor Red Cells Platelets/FFP

B A O AB

A B O AB
 Transfusion support for HSCT recipients

• Pre-transplantation (Phase I) - from the time recipient is prepared for

HCT transplant until initiation of transplant.
• Peri-transplantation (Phase II) - initiation of chemotherapy until
engraftment
• Post-engraftment (Phase III) - after engraftment where forward and
reverse group of recipient is consistent with donor’s ABO group

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 Laboratory process in phase I and II and
transfusion support
• ABO RhD blood group and antibody screening
• Flagging Patient on LIMS
• Pre transplant titre Anti-A and Anti-B by IAT where indicated
• BMT protocol notification received by Laboratory
• Patient details updated and flagged on LIMS
• Supporting patients with transfusion:
• recipient antibodies are still detectable
• donor lymphocytes produce antibodies against recipient RBC
• chimera: recipient and donor type RBC detectable
• forward and reverse types don’t match

• Patient discharged- Shared care form

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 Laboratory process in phase III
Post-Engraftment
• Complete Engraftment
• Patient RBC types like donor RBC
• Patient ABO antibodies are same as donor.
• Criteria for blood group conversion
• No recent history of transfusion
• DAT must be negative
• No detectable ABO antibodies to the donor by IAT at 37 oC
• Requires confirmed new blood type on 2 separate occasions to switch blood
products to donor type
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 Potential Immunohaematologic Complications
after ABO Mismatch
Major ABO Incompatibility
PATHOPHYSIOLOGY
Immediate:
• acute haemolysis of infused donor red cells within the graft
Delayed:
• haemolysis of red cells produced by engrafted marrow (recipient ABO antibodies
may persist 3-4 months
• delayed onset of erythropoiesis (40-60 days)
• Pure red cell aplasia

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 Potential Immunohaematologic Complications
after ABO Mismatch
Major ABO Incompatibility (continued)
SEROLOGICAL FINDINGS:
• DAT positive for C3d, IgG or both; eluate will show Anti-A and/or Anti-B
• DAT positive for C3d, IgG or both; antibody to non-abo red cell antigen(s) identified in eluate
and patient plasma.

POTENTIAL INTERVENTIONS :
• Red blood cell reduction of stem cell product
• Reduction in isohaemaglutinins of recipient using therapeutic plasma exchange
• Promotion of donor erythropoiesis via erythropoietin administration
• Select and transfuse components compatible with donor and recipient

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 Potential Immunohaematologic Complications
after ABO Mismatch
Minor ABO Incompatibility
PATHOPHYSIOLOGY
Immediate
• Haemolysis of recipient’s erythrocytes caused by alloantibodies in transfused
donor plasma.
Delayed
• Haemolysis, occurs 7-14 days after transplant, due to rapid generation of
antibodies by donor lymphocytes (passenger B-cells)

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 Potential Immunohaematologic
Complications after ABO Mismatch
Minor ABO Incompatibility (continued)
SEROLOGICAL FINDINGS
• DAT positive for C3d, IgG or both: antibody to non-abo red cell antigens(s) identified
in eluate and patient plasma
• DAT positive for C3d, IgG or both Anti-A and /or Anti-B present in eluate

POTENTIAL INTERVENTIONS
• plasma reductions
• transfuse components with plasma which is compatible with donor and recipient RBC’s

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 Potential Immunohaematologic Complications
after ABO Mismatch
Bidirectional ABO Incompatibility
PATHOPHYSIOLOGY
Immediate
• Haemolysis caused by donor and/or recipient’s red cells antibodies
Delayed:
• Haemolysis caused by donor and/or recipient’s red cells antibodies
• delayed engraftment of RBC’s
• Pure red cell aplasia
SEROLOGICAL FINDINGS
• this a combination of major and minor aetiologies.
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 Non-ABO & RH Incompatibilities

RBC ALLOANTIBODY INCOMPATIBILITY

•Major - Recipient has antibodies to donor antigen
•Minor - Donor has antibodies to recipient RBC antigen

RHD INCOMPATIBILITY
• Major - DONOR is RhD positive and a RECIPIENT is RhD negative
• Minor - DONOR is RhD negative and the RECIPIENT is RhD positive.

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 Transfusion Support for HSCT Recipients

Red Blood Cells

• 70g/l in stable, non-postoperative adult HSCT
• 80g/l for adults with pre-existing heart disease and or risk of end organ damage

Platelets
• 10 X 10^9/L for prophylaxis
• 20 X 10^9/L in febrile patients
• 50 X 10^9/L in bleeding patients

Platelet Refractoriness
• HLA alloimmunisation in haematology patients
• Increase platelet transfusion requirements

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 Challenges in the Laboratory

• Patient’s special requirements

• Issuing out wrong ABO blood to patients
• Patients with long absence, No history
• Discrepant ABO blood group results
• HLA matched platelet support
• Conversion of patient group to donor’s
• Shared care forms

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QPulse Doc No: CF-HAE-0025 Edition: 3 Issue Date: 31-Mar-2016 Review Date: 31-Mar-2018

Controlled Document: DO NOT PHOTOCOPY Print new copies from Y:\Haematology\Forms and Letters\ Blood Products\SharedCareSpecialBloodRequirements.doc
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 CONCLUSIONS

Overall clinical and laboratory management of ABO incompatible HSCT is

complex and depends on many factors notably:
• The source of the transplant
• The conditioning regimen
• Concise transfusion policy
• Communication between clinical teams and BTL
• The clinical status of the patient

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 References
• Seebach JD, Stussi G, Passweg JR, et al; GVHD Working Committee of Center for International Blood and Marrow
Transplant Research. ABO blood group barrier in allogeneic bone marrow transplantation revisited. Biol Blood
Marrow Transplant. 2005;11(12):1006-1013.
• Rowley SD (2001). Hematopoietic stem cell transplantation between red cell incompatible donor-recipient pairs.
Bone Marrow Transplant 28: 315-321.
• Szczepiorkowski ZM. Transfusion Support for Heamotpoietic Transplant Recipients. in: Roback J. ed. Technical
manual 16th ed. Bethesda MD: American Association of blood banks, 2008. 679-96.
• 3. Cunard R, Marquez II, Ball ED, Nelson CL, Corringham S, Clopton P, Sanchez AP, Lane T, Ward DM.
Prophylactic red blood cell exchange for ABO-mismatched hematopoietic progenitor cell transplants. Transfusion.
2014 Jul;54(7):1857-63.
• Cohn CS, Transfusion support issues in hematopoietic stem cell transplantation. Cancer Control. 2015 Jan;22(1):52-
9.
• Tormey CA, Synder el. Transfusion Support for the Oncology patient. in: Toby L. Simon et al. ed. Rossi’s
Priniciples of Transfusion Medicine 4th ed. American Association of Blood Banks, 2008. 482-97.
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 CASE STUDY 1

• 48 year old male AML patient blood group : A RHD NEGATIVE

BMT DONOR 1= O RHD POS
BMT DONOR 2= A RHD POS
BMT date : 23.08.2012
 Which products would you select for this patients
 Can you predict the outcome of this transplant ?
Any Questions?

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Thank You.

K. Amenyah, KCH NHS