The primary objectives of this proposal are to evaluate the use of leukocyte-depleted blood products and/or 8-methoxypsoralen (8-MOP) & UV-A pre-treated random donor platelets (RDP) to prevent primary alloimmunization and to investigate the use of HLA- matched vs random single donor platelets and red cells to prevent broad sensitization among patients with prior alloimmunization. the distinction of patients with and without prior alloimmunization is critical because of their different immunological behavior in response to blood transfusions. Prior sensitization will be determined by conventional cytotoxicity and by flow cytometry. for the first objective, non-alloimmunized patients with newly diagnosed acute non-lymphocytic leukemia will be randomized into 3 treatment groups: 1) Group A will receive only leukocyte-depleted RDP and red cells. 2) Group B will receive only RDP with leukocytes inactivated by 8-MOP and UV-A and leukocyte-depleted red cells. 3) Group C will receive regular RDP and red cells as control. Special emphasis will be made on accurate quantitation of leukocytes that remain in the leukocyte- depleted products so that a potentially immunogenic threshold can be established. A novel method to achieve precise quantitation of low numbers of white cells in leukocyte depleted blood is described. Antibodies will be measured weekly by lymphocytotoxicity and flow cytometry. HLA or non-HLA specificity will be determined by neutralization of antibody with purified HLA antigens. For the second objective, patients with prior allosensitization will be randomized into 2 groups. 1) Group A will receive HLA matched single donor blood products. 2) Group B will receive random single donor blood products. Changes of antibody titers will be measured by flow cytometry and by panel lymphocytotoxic antibody reactivity. Retrospective crossmatches will be performed to determine if 10W level anti-donor antibodies consistently induce poor transfusion responses or acceptable increments can still occur in their presence. The results of the proposed studies will not only allow us to evaluate methods to prevent allosensitization but they will also further our understanding about the role of leukocytes in triggering humoral immune responses to HLA antigens.
| Slichter, Sherrill J; Bolgiano, Douglas; Kao, Kuo-Jang et al. (2011) Persistence of lymphocytotoxic antibodies in patients in the trial to reduce alloimmunization to platelets: implications for using modified blood products. Transfus Med Rev 25:102-10 |
| Slichter, Sherrill J; Davis, Kathryn; Enright, Helen et al. (2005) Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood 105:4106-14 |
