This proposal is submitted in response to RFA NIH 88-HL-12B to serve as a Clinical Center in a study designed to determine practical methods for reducing the incidence of alloimmunization and refractoriness to platelet transfusions in multitransfused patients with acute nonlymphocytic leukemia (ANLL). Transfusion therapies under consideration include use of: platelet concentrates from random, single donors prepared by apheresis techniques; leukocyte-poor platelet concentrates; and platelet concentrate exposed to ultraviolet irradiation. The incidence of alloimmunization in patients assigned to various protocols will be determined and will be compared with that of a """"""""control"""""""" group treated with standardly prepared platelet concentrate. The study will be prospective, randomized, and single-blinded. Patients will be assigned to specific study arms on the basis of demographic information including history of pregnancy, etc. by the Coordinating Center. Patients with a new diagnosis of ANLL who undergo induction therapy at selected hospitals in Milwaukee and at the University of Wisconsin Hospitals in Madison will be eligible for the study. Platelet transfusions will be prescribed for therapeutic or prophylactic indications and will be prepared by The Blood Center of Southeastern Wisconsin and the American REd Cross Blood Services-Badger Region. Alloimmunization and refractoriness to platelet transfusions will be determined by clinical and laboratory parameters. Determination of whether refractoriness is related to immunologic or non-immunologic factors (e.g., sepsis, fever, etc.) may be clarified by the response to HLA-matched platelet transfusions. Both regional blood centers maintain an extensive list of HLA-typed donors and should be able to obtain an adequate number o HLA-matched platelet transfusions on a timely basis. Laboratory assessment of alloimmunization will be determined by assays for complement-fixing and non-complement-fixing antibodies reactive with class I HLA determinants and other alloantigens expressed on platelets. Non-HLA alloantigens expressed on platelets are a major research interest of The Blood Center of Southeastern Wisconsin. The Blood Center would be willing to provide reference testing for allo-antibodies reactive with such determinants if requested. Alloimmunization is a vexing problem for clinicians treating patients with ANLL. The proposed study should resolve existing questions about the effectiveness of methods for preventing or reducing its occurrence.
| 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 |
| Enright, Helen; Davis, Kathryn; Gernsheimer, Terry et al. (2003) Factors influencing moderate to severe reactions to PLT transfusions: experience of the TRAP multicenter clinical trial. Transfusion 43:1545-52 |
