Persistence of HTLV-I in blood components after leukocyte depletion

Pennington, J. H.; Taylor, Graham P.; Sutherland, Janet; Davis, Ricardo; Seghatchian, Jerhard; Allain, Jean‐Pierre; Williamson, Lorna M.

doi:10.1182/blood.v100.2.677

Cited by 48 publications

(31 citation statements)

References 30 publications

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“…Evidence for possible monocyte activation comes from recent observations reporting cytokine production by PBMCs exposed to CMV for only 18 hours, a CD14-dependent phenomenon. 20 The less efficient removal of CMV by platelet than by whole blood filtration was also found with HTLV, 12 although one study of filtration and centrifugal apheresis LD achieved approximately 3 10 log CMV removal. 11 We noted greater plasma contamination associated with reduced viral recovery from filters with platelet LD, raising the possibility of CMV release from leukocyte cytoplasm 21 during filtration.…”

Section: Resultsmentioning

confidence: 98%

“…We have previously used infected T lymphocytes and real-time PCR to assess human T-cell leukemia virus-I (HTLV-I) removal by LD. 12 A CMV-infected T-cell line has also been described to measure CMV removal, 13 but T cells are not a major physiological reservoir of CMV. We have therefore modified a previously described system 14 to generate CMV-infected mononuclear cells, including CD14 ϩ monocytes, for spiking into blood donations prior to LD.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 The cause of the discrepancy between monocyte and CMV removal is not clear, but with HTLV-infected T cells and similar filters, overall T-cell reduction was also 1 log greater than HTLV Tax removal. 12 It may be that monocytes activated by CMV infection are removed less well by filters than noninfected cells. Evidence for possible monocyte activation comes from recent observations reporting cytokine production by PBMCs exposed to CMV for only 18 hours, a CD14-dependent phenomenon.…”

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confidence: 99%

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Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR

Visconti

Pennington

Garner

et al. 2004

Blood

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To assess removal of cytomegalovirus (CMV) by leukocyte depletion (LD) filters, we developed a spiking model of latent virus using peripheral blood mononuclear cells (PBMCs) infected by coculture with CMV-infected human fibroblasts. Infected PBMCs were purified by dual magnetic column selection and then spiked into whole blood units or buffy coat pools prior to LD by filtration. CMV load and fibroblast contamination were assessed using quantitative CMV DNA real-time PCR and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of mRNA encoding the fibroblast-specific splice variant of prolyl-4-hydroxylase, respectively. After correcting for fibroblast-associated CMV, the mean CMV load was reduced in whole blood by LD from 7.42 10 2 to 1.13 copies per microliter (2.81 10 log reduction) and from 3.8 10 2 to 4.77 copies per microliter (1.9 10 log reduction) in platelets. These results suggest that LD by filtration reduces viral burden but does not completely remove CMV from blood components. (Blood. Introduction Primary cytomegalovirus (CMV) infection results in lifelong carriage of latent virus, notably in CD14 monocytes. 1 Reactivation of donor CMV following transfusion 2 is avoided by selecting CMV-seronegative donors for vulnerable patients. Because universal leukocyte depletion (LD) has been widely implemented, it is debated whether LD alone could provide equivalent protection. 3,4 Eight studies have shown no transmissions following prestorage LD, 5,6 but a recent study reports increased transmission from LD CMV-seropositive components. 7 Quantitative real-time polymerase chain reaction (PCR) has the dynamic range to assess CMV removal by LD, 8,9 but due to low copy number, we and others 9 have failed to detect viremia in seropositive donors, and even optimal CMV PCR would require virtually all leukocytes in an LD component (less than 10 6). 10 We found techniques reported to increase CMV copy number (pollen, 11-interferon, hydrocortisone, granulocyte-macrophage colony-stimulating factor [GM-CSF], and allogeneic cells 2) to be insufficiently robust for assessment of LD. We have previously used infected T lymphocytes and real-time PCR to assess human T-cell leukemia virus-I (HTLV-I) removal by LD. 12 A CMV-infected T-cell line has also been described to measure CMV removal, 13 but T cells are not a major physiological reservoir of CMV. We have therefore modified a previously described system 14 to generate CMV-infected mononuclear cells, including CD14 monocytes, for spiking into blood donations prior to LD. Study design With ethics committee approval and donor consent, 450-mL blood donations from 6 CMV-seronegative donors were collected into citrate phosphate dextrose. Peripheral blood mononuclear cells (PBMCs) were prepared from a 24 mL aliquot by density gradient separation (mean yield, 1.52 10 7 0.27 10 7) and cultured for 12 hours with 2 10 6 human embryonic fibroblasts infected with human CMV strain AD169. PBMCs were separated from fibroblasts by double selection using magnetic beads coate...

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR

Visconti

Pennington

Garner

et al. 2004

Blood

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“…A similar situation exists for HTLVI and HTLVII. One experiment demonstrated that, following leukocyte depletion, HTLVI proviral DNA remained detectable (albeit at reduced levels) in 13 of 16 whole blood samples, all filtered platelets spiked with MT-2 cells, and in blood from 3 of 5 asymptomatic HTLVI carriers (the infectivity of the filtered components is not known) [47]. [48].…”

Section: Leukocytes and Latent Virusesmentioning

confidence: 99%

Why ‘Safer than Ever’ May Not Be Quite Safe Enough

Barbara¹

2004

Transfus Med Hemother

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Although the blood supply in developed countries is now very safe, residual microbial risks can still be identified. These are mainly due to bacteria. A wide range of sophisticated (and resource-consuming) interventions are in place which are generally successful in dealing with the risk from known viral agents. However, newly emergent viral risks can usually only be addressed after they have been shown to transmit and after tests have been developed. Parasitic and, even more significantly, bacterial risks (especially in platelet preparations which have to be stored at 22 °C) have often not been managed as effectively as the risk for the ‘known’ viruses such as HIV, HBV and HCV. Pathogen inactivation (PI) offers an approach to remove the vast majority of microbial risks. In the future, if the full inventory of transfusable components can be effectively pathogen-inactivated, PI could form an alternative basis for blood safety in terms of microbial risk, rather than just another incremental safety intervention.

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“…EBV titers are also significantly reduced by RBC filtration, rendering most filtered units EBV-negative [28] . HTLV-I titers decline as well after LR, though not completely [29] . Other blood borne infectious diseases curbed by RBC filtration include malaria, leishmaniasis, human granulocytic anaplasmosis, and Yersinia enterocolitis [30–33] .…”

Section: Introductionmentioning

confidence: 99%

Role of Leukoreduction of Packed Red Blood Cell Units in Trauma Patients: A Review

Kim

Xia

Chang

et al. 2016

International Journal of Hematology Research

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Hemorrhagic shock is a leading cause of mortality within the trauma population, and blood transfusion is the standard of care. Leukoreduction filters remove donor leukocytes prior to transfusion of blood products. While the benefits of leukocyte depletion are well documented in scientific literature, these benefits do not translate directly to the clinical setting. This review summarizes current research regarding leukoreduction in the clinical arena, as well as studies performed exclusively in the trauma population.

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Persistence of HTLV-I in blood components after leukocyte depletion

Cited by 48 publications

References 30 publications

Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR

Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR

Why ‘Safer than Ever’ May Not Be Quite Safe Enough

Role of Leukoreduction of Packed Red Blood Cell Units in Trauma Patients: A Review

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