Alloimmunization and Refractoriness to Allogeneic Platelet Transfusions

F OUR YEARS AGO an editorial in Blood identified a number of issues concerning policy decision-making about the clinical use of leukodepleted cellular blood products to prevent HLA-alloimmunization and refractoriness to transfused allogeneic platelets.’ In that editorial, Schiffer concluded that it was premature to recommend platelet leukodepletion for routine use. The issues identified in that editorial included the following: (1) The applicability of the available results to the general leukemic population, because most studies had been done using highly selected patient populations. (2) The lack of available data on the effectiveness of leukodepletion to prevent HLA-alloimmunization and platelet refractoriness in individuals who were already alloimmunized, including those who had been transfused previously andor females with a history of prior pregnancies. (3) The inconsistency in the degree of leukodepletion of the cellular blood products used in the various studies reported. (4) The economic implications of leukodepleting all cellular blood products when the potential clinical benefit might be available to only a small percentage of patients who would be receiving such products. During the 4 years since that editorial, three more clinical trials reporting on the use of leukodepleted cellular blood products have appeared.24 These include the article by Sintnicolaas et a1 in this issue of Blood.4 In addition, several international forums and consensus conferences have been held to try to deal with the indications for the clinical use of leukodepleted cellular blood produ~ts.~” Are the answers to the unresolved issues, previously identified by Schiffer, on which to make policy decisions about the use of leukodepleted cellular blood products now available? As will be outlined below, even though much of the available data are tantalizing, the actual clinical benefit for the leukodepletion of cellular allogeneic blood products has not been established for most indications suggested for their use. Research methodologists and epidemiologists have provided a very useful framework that can be applied to try to address the issues relating to the clinical use of leukodepleted cellular blood p r o d ~ c t s . ~ , ~ This approach involves the careful assessment of the published data to determine: the validity of the methodology used; the magnitude of the treatment effect; and whether the results of a particular study are relevant to the care given to a specific patient. This methodologic framework for critical appraisal has been used to evaluate