OVERCOMING GRAFT FAILURE AFTER HLA MISMATCHED STEM CELL TRANSPLANT (SCT) WITH POSITIVE CROSSMATCH.

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OVERCOMING GRAFT FAILURE AFTER HLA MISMATCHED STEM CELL TRANSPLANT (SCT) WITH POSITIVE CROSSMATCH.
Oksana Gudzowaty , Carolyn Whitsett , S. Yoon Choo , Yelena Sinitsyn and Luis Isola . New York NY, Mount Sinai Medical Center, 10029, Tissue Typing Laboratory and Bone Marrow Transplant Program .

A 54 y/o female with severe aplastic anemia, refractory to platelet transfusions due to anti-HLA and anti-platelet specific antibodies, received a PBSC transplant from her haploidentical son. Prior to conditioning, the patient received IVIG for immune modulation. She was transplanted with 10⁷ CD34⁺ selected cells/kg, after conditioning with thiotepa, melphalan, fludarabine, and rabbit ATG.
Lymphocytotoxic antibody screen (CDC/AHG) of pre-transplant serum detected possible HLA-A2 specificity (50% PRA, titer of 16), with A*02 present on the donor's paternal haplotype. PRA of post-transplant (d20) serum dropped to 29%. On d28 post-SCT, ANC was still <500 µL. Due to engraftment failure, the patient received rituximab, plasmapheresis, high dose IVIG, and a boost of 4.5x10⁶ CD34⁺ selected cells/kg. Nine days post-boost (d36), ANC was 10,000/µL, with FISH demonstrating 100% donor cells in the recipient's peripheral blood.
Retrospective crossmatches (CDC/AHG) were performed on day of boost using CD34⁺ enriched donor stem cells, as well as donor T and B cells. Pre-transplant serum was positive with CD34⁺ cells and B cells (both 1:64). Post-transplant (d20) and post-plasmapheresis sera were negative with CD34⁺ cells, but still positive with B cells (1:32). T cell crossmatches were negative with all sera.
The timing of engraftment in this patient suggests that suppression of humoral immunity was critical to overcome graft failure. Crossmatching in a heavily transfused, HLA alloimmunized patient receiving a mismatched SCT may provide useful information to optimize immunosuppressive therapy and donor selection.