Interesting Case Conference 9-10-14

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

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

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

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; 14:165-170

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;46:1167-1185

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

http://www.gene-quantification.de/qpcr2009/Ganderton-qPCR-2009.pdf

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

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: 1598-1601 Am J Hematol 2009;84:771-772

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