1. Interesting Case Conference

2. The Case 17 y/o female with AML, blood type O positive
Underwent AB positive bone marrow transplant, HLA matched at A, B, C, DR, and DQ on 5/14/14
Neutrophil engraftment 6/5/14; platelet engraftment still pending

3. Forward/Reverse Type A B A1C BC 8/1/14 1+ 2+ 8/8/14 M3 8/15/14 M1 W+1+ 2+
8/8/14 M3
8/15/14 M1 W+
8/19/14
8/26/14

4. What caused the change? She received multiple type O transfusions, and
on 8/15 she received
Gamunex
Two possibilities:
Graft failure
Forward type reflects transfused type O cells
and reverse type reflects IVIG

5. Causes of graft failure
HLA mismatch
0.1% failure in HLA identical sibling tx, vs 5% failure in HLA mismatched unrelated donor
ABO incompatibility
7.5% failure in ABO mismatch, compared to 0.6% in ABO compatible
Recipients previously sensitized by transfusion or pregnancy
Antibody mediated
Low dose transplant
Reduced intensity conditioning
Recipient T and NK cells are generally thought to be primary effector cells
Biol Blood Marrow Transplant 2008; 14:

6. Major ABO incompatible grafts
Studies have not shown consistent delay in neutrophil engraftment
Several studies have shown delayed platelet engraftment and increased platelet transfusion requirements
15-fold higher risk of engraftment failure
Bone Marrow Transplantation 2011;46:

7. Engraftment studies
DNA isolated from the WBCs of the patient and donor prior to the transplantation
Multiplex fluorescent PCR is performed to amplify 15 independently segregating polymorphic loci and one gender-specific locus, Amelogenin (AMEL). Amplicons of varying lengths are detected by capillary electrophoresis and analyzed to determine differences between donor/recipient
May be performed on blood or bone marrow
Enriched subpopulations of hematopoietic cells (CD3+ T lymphocytes and CD33+ myeloid cells) may also be assayed to increase the sensitivity compared to whole blood
Reduced CD3+ chimerism is strongly associated with graft failure

10. Our patient 6/17: BM showed 100% donor 8/8: PB CD33+ showed 100% donor

11. IVIG
IVIG may passively confer alloantibodies against A, B, D, K, and other blood group antigens
Clinically significant hemolysis due to IVIG is rare, but may occur in up to 1.6% of patients
More likely in females, non-O blood group, underlying inflammatory state, or large doses of IVIG
IVIG anti-A and anti-B hemagglutinin titers in these cases may be as low as 1:2 to 1:8
Transfusion 2008;48:
Am J Hematol 2009;84:

12. Clin J Am Soc Nephrol 2009;4: 1993-1997