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Leukofiltration plus pathogen reduction prevents alloimmune platelet refractoriness in a dog transfusion model

Sherrill J. Slichter, Esther Pellham, S. Lawrence Bailey, Todd Christoffel, Irena Gettinger, Lakshmi Gaur, Yvette Latchman, Karen Nelson and Doug Bolgiano

Key points

  • Eight weekly transfusions of filter leukoreduced + pathogen-reduced donor platelets were accepted by 31/32 (97%) recipient dogs.

  • Among accepting recipients, none developed lymphocyte and only 2 had platelet antibodies not associated with platelet refractoriness.

Abstract

Human Lymphocyte Antigen (HLA) alloimmunization to filter leukoreduced (F-LR) platelets occurs in about 18% of immunosuppressed thrombocytopenic hematology/oncology patients and represents a significant challenge for effective chemotherapy. In a dog platelet transfusion model, we have evaluated other methods of preventing alloimmune platelet refractoriness and demonstrated that successful methods in our dog model are transferable to man. In the present study, donor/recipient pairs were dog lymphocyte antigen (DLA) DR-B incompatible (88% of the pairs), and recipient dogs received up to 8 weekly treated transfusions from a single donor (a highly immunogenic stimulus), or until platelet refractoriness. Continued acceptance of F-LR platelets occurred in 6/13 recipients (46%), but neither γ-irradiation (γ-I, 0/5) nor Mirasol™ pathogen reduction (MPR, 1/7) treatment of donor platelets prevented alloimmune platelet refractoriness. Combining γ-I with F-LR was associated with only 2/10 (20%) recipients accepting the transfused platelets. Surprisingly, F-LR platelets that then underwent MPR were accepted by 21/22 (95%) recipients (p<0.001 versus F-LR+γ-I recipients). Furthermore, 7/21 (33%) of these accepting recipients demonstrated specific tolerance to 8 more weekly donor transfusions that had not been treated. In addition, platelet concentrates prepared from F-LR+MPR whole blood were also non-immunogenic; i.e., 10/10 (100%) recipients accepted donor platelets. Overall, 31/32 (97%) recipients accepted F-LR+MPR platelets; none developed antibodies to donor lymphocytes. These data are the highest rate of acceptance for platelet transfusions reported in either animals or man. This approach to platelet transfusion may be particularly important when supporting patients with intact immune systems, such as in myelodysplastic syndromes.

  • Submitted July 7, 2016.
  • Accepted June 28, 2017.