Methods of preventing platelet alloimmunization and alloimmune platelet refractoriness and induction of tolerance in transfused recipients

Abstract

Methods and compositions for the prevention or reduction of platelet transfusion associated complications are provided. The subject methods include modifying donor whole blood or platelets prior to transfusion to prevent or reduce alloimmune platelet refractoriness.

What is claimed: 
     
         1 . A method for reducing risk of platelet alloimmunization upon transfusion, the method comprising:
 filtering whole blood from a donor through a leukoreduction filter;   performing pathogen reduction on the whole blood by adding riboflavin to the whole blood and irradiating the whole blood and riboflavin with UV light and thereby substantially eliminating donor lymphocytes from the whole blood; and   transfusing the filtered and pathogen reduced whole blood into a recipient, wherein the transfused whole blood has an acceptance rate of 90% or higher wherein following the transfusion, the recipient is antibody negative to donor lymphocytes; thereby reducing the risk of the recipient developing platelet alloimmunization upon receiving transfused donor platelets.   
     
     
         2 . The method according to  claim 1 , wherein the transfused whole blood has an acceptance rate of 93% or higher. 
     
     
         3 . The method according to  claim 1 , wherein the transfused whole blood has an acceptance rate of 95% or higher. 
     
     
         4 . The method according to  claim 1 , wherein the risk of the recipient developing platelet alloimmunization upon receiving transfused donor platelets is reduced by 90% or more. 
     
     
         5 . The method according to  claim 1 , wherein the leukoreduction filter is Terumo Immuflex WB-SP. 
     
     
         6 . A method of preparing a toleragenic platelet composition reduced of alloimmunizing cells, the method comprising:
 filtering whole blood from a donor to remove alloimmunizing cells;   performing Mirasol pathogen reduction (MPR) on the whole blood by adding riboflavin to the whole blood and irradiating the whole blood and riboflavin with UV light thereby substantially eliminating donor lymphocytes from the whole blood;   recovering the filtered and pathogen reduced whole blood as the toleragenic platelet composition; and   estimating the recipient acceptance of donor platelets of the toleragenic platelet composition, wherein the toleragenic platelet composition has an estimated recipient acceptance of donor platelets of 90% or more.   
     
     
         7 . The method according to  claim 6 , wherein the toleragenic platelet composition has an estimated recipient acceptance of donor platelets of 93% or more. 
     
     
         8 . The method according to  claim 6 , wherein the toleragenic platelet composition has an estimated recipient acceptance of donor platelets of 95% or more. 
     
     
         9 . The method according to  claim 6 , wherein the filtering is performed with a leukoreduction filter. 
     
     
         10 . The method according to  claim 6 , wherein performing the pathogen reduction comprises γ-irradiating the whole blood. 
     
     
         11 . The method according to  claim 6 , wherein the filtering is performed with a Terumo Immuflex WB-SP filter. 
     
     
         12 . The method according to  claim 6 , further comprising the steps of preparing platelet rich plasma or a platelet concentrate from the filtered and irradiated whole blood; and recovering the platelet rich plasma or platelet concentrate as the toleragenic platelet composition. 
     
     
         13 . A method of preventing platelet refractoriness in a recipient receiving platelets from an antigenically mismatched donor, the method comprising:
 filtering whole blood from a donor through a leukoreduction filter;   performing pathogen reduction on the whole blood by adding riboflavin to the whole blood and irradiating the whole blood and riboflavin with UV light and thereby substantially eliminating donor lymphocytes from the whole blood; and   transfusing the filtered and pathogen reduced whole blood into the recipient, wherein the transfused whole blood has an acceptance rate of 90% or higher, wherein following the transfusion the recipient is antibody negative to donor lymphocytes, and wherein the transfused platelets do not cause the recipient to develop platelet refractoriness.   
     
     
         14 . The method according to  claim 13 , further comprising the steps of preparing platelet rich plasma or a platelet concentrate from the filtered and irradiated whole blood; and transfusing the platelet rich plasma or platelet concentrate into the recipient. 
     
     
         15 . A toleragenic platelet composition prepared by a process, the process comprising the steps of:
 filtering whole blood through a leukoreduction filter; and   performing Mirasol pathogen reduction (MPR) on the whole blood by adding riboflavin to the whole blood and irradiating the whole blood and riboflavin with UV light and thereby substantially eliminating donor lymphocytes from the whole blood, wherein performing the pathogen reduction does not comprise γ-irradiating the whole blood.   
     
     
         16 . The toleragenic platelet composition according to  claim 15 , wherein the process comprises estimating the recipient acceptance of donor platelets of the filtered and pathogen reduced whole blood to be 90% or more. 
     
     
         17 . The toleragenic platelet composition according to  claim 15 , wherein the leukoreduction filter is Terumo Immuflex WB-SP. 
     
     
         18 . The toleragenic platelet composition according to  claim 15 , wherein the UV light is at a wavelength of between 290-370 nm. 
     
     
         19 . The toleragenic platelet composition according to  claim 15 , comprising the further step of preparing platelet rich plasma or a platelet concentrate from the filtered and irradiated whole blood. 
     
     
         20 . The toleragenic platelet composition according to  claim 15 , wherein the composition does not produce an immune reaction in a recipient receiving the platelet composition.