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

K. Amenyah, KCH NH
 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)

K. Amenyah, KCH NH
 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.

K. Amenyah, KCH NH
 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.

K. Amenyah, KCH NH
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)
K. Amenyah, KCH NH
 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

K. Amenyah, KCH NH
 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

K. Amenyah, KCH NH
Transfusion support for HSCT
recipients
Major
Recipient
ABO
Donor
incompatible
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

K. Amenyah, KCH NH
 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

K. Amenyah, KCH NH
 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
K. Amenyah, KCH NH
 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

K. Amenyah, KCH NH
 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

K. Amenyah, KCH NH
 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)

K. Amenyah, KCH NH
 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
K. Amenyah, KCH NH
 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.
K. Amenyah, KCH NH
 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.

K. Amenyah, KCH NH
 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
K. Amenyah, KCH NH
 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

K. Amenyah, KCH NH
QPulse Doc No: CF-HAE-0025 Edition: 3 Issue Date: 31-Mar-2016 Review Date: 31-Mar-2018

K. Amenyah, KCH NH
Controlled Document: DO NOT PHOTOCOPY Print new copies from Y:\Haematology\Forms and Letters\ Blood Products\SharedCareSpecialBloodRequirements.doc
 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

K. Amenyah, KCH NH
 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 4 th ed. American Association of Blood Banks, 2008. 482-
97.

K. Amenyah, KCH NH
 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?

K. Amenyah, KCH NH
Thank You.

K. Amenyah, KCH NH