1. Abo incompatible stem cell transplant: laboratory side
Kenneth Amenyah
Operations Manager
Blood Transfusion Laboratory (Viapath)
King’s College Hospital NHS Trust
February 2017

2. 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 NHS

3. 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 NHS

4. 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 NHS

5. 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 NHS

6. 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 NHS

7. 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 NHS

8. Classification of HSCT by ABO blood group Donor and Recipient
ABO Group
Donor ABO group O A B AB
Identical
Major
Minor
Bidirectional
K. Amenyah, KCH NHS

9. Transfusion support for HSCT recipients Major ABO incompatible
Donor
Red cells
Platelets/FFP O A
A, AB B
B, AB AB

10. Transfusion support for HSCT recipients Minor ABO incompatible
Donor
Red Cells
Platelets/FFP A O
A, AB B
B, AB AB

11. Transfusion support for HSCT recipients Bidirectional ABO incompatible
Donor
Red Cells
Platelets/FFP B A O AB

12. 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 NHS

13. 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 NHS

14. 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 37oC
Requires confirmed new blood type on 2 separate occasions to switch blood products to donor type
K. Amenyah, KCH NHS

15. 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 NHS

16. 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 NHS

17. 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 NHS

18. 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 NHS

19. Potential Immunohaematologic Complications after ABO Mismatch
Bidirectional ABO Incompatibility
PATHOPHYSIOLOGY
Immediate
Haemolysis caused by donor and/or recipient’s red cells antibodies
Delayed:
delayed engraftment of RBC’s
Pure red cell aplasia
SEROLOGICAL FINDINGS
this a combination of major and minor aetiologies.
K. Amenyah, KCH NHS

20. 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 NHS

21. 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 NHS

22. 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 NHS

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

24. 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 NHS

25. 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):
Rowley SD (2001). Hematopoietic stem cell transplantation between red cell incompatible donor- recipient pairs. Bone Marrow Transplant 28:
Szczepiorkowski ZM. Transfusion Support for Heamotpoietic Transplant Recipients. in: Roback J. ed. Technical manual 16th ed. Bethesda MD: American Association of blood banks,
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 Jul;54(7):
Cohn CS, Transfusion support issues in hematopoietic stem cell transplantation. Cancer Control 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,
K. Amenyah, KCH NHS

26. 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 :
Which products would you select for this patients
Can you predict the outcome of this transplant ?

27. Any Questions?
K. Amenyah, KCH NHS

28. Thank You.
K. Amenyah, KCH NHS