Leukocyte reduction and HTLV-I: is the glass half empty or half full?

We read with interest the recent article by Pennington et al. 1 Based on the ability to detect Tax DNA in the blood of asymptomatic carriers with proviral loads exceeding 10 8 DNA copies/L, the authors conclude that leukocyte depletion (LD) may not provide complete protection from human T-cell leukemia virus–I (HTLV-I) transmission by transfusion. Lau et al 2 proved that cytomegalovirus (CMV)–infected blood, another example of a cell-borne viral infection, transfected with as many as 3 ϫ 10 8 infected cells, contains a residual of 10 5 viral copies following LD, consistent with the present study's observations. These findings were confirmed in asymptomatic seropositive donors by Dumont et al. 3 However, in spite of the residual polymerase chain reaction (PCR) detectability of the CMV DNA in the postfiltration blood, little controversy exists concerning the ability of LD to greatly reduce the potential for transfusion-transmitted CMV infection. 4,5 Okochi and Sato 6 conclude that approximately 10 8 infected lymphocytes are required to transmit HTLV-I infection by transfusion. This conclusion is further supported by the fact that plasma derived simultaneously from donations of whole blood whose red cells have transmitted HTLV-I infection have not transmitted the infection nor, as stated by the authors, has plasma ever been documented to transmit the infection. A unit of non-LD plasma delivers an average 3 ϫ 10 6 leukocytes to a recipient. 7 Kobayashi et al 8 confirmed the infectivity of 7 units of native red cells from HTLV-I–positive donors using a syncytium induction assay in which cocultivation of HTLV-I–permissive (ME-80) cells and donor lymphocytes effect the development of multinucleated giant cells. Following LD, only 1 of the 7 filtered units showed infectivity using this assay. Shinzato et al 9 quantified the HTLV-I viral genome load in the blood of 133 asymptomatic carriers and found that 95% of the individuals had 10 infected cells per 100 peripheral blood mono-nuclear cells (PBMCs), which approximates less than 10 8 cells per unit of blood. Levin et al found the number of infected cells to be as low as 1 per 10 000 PBMCs in patients with HTLV-I–associated disease. 10 Accepting the findings of the current study (ie, LD imposes a 3-4 log 10 viral titer reduction), the residual number of proviral genomes in the blood of asymptomatic carriers is substantially less than that of plasma from infected donors and the infectious viral load requirement of Shinzato et …