Impact of Transfusion on Cancer Growth and Outcome.

For many years, transfusion of allogeneic red blood cells, platelet concentrates, and plasma units has been part of the standard therapeutic arsenal used along the surgical and nonsurgical treatment of patients with malignancies. Although the benefits of these blood products are not a matter of debate in specific pathological conditions associated with life-threatening low blood cell counts or bleeding, increasing clinical evidence is nevertheless suggesting that deliberate transfusion of these blood components may actually lead to negative clinical outcomes by affecting patient's immune defense, stimulating tumor growth, tethering, and dissemination. Rigorous preclinical and clinical studies are needed to dimension the clinical relevance, benefits, and risks of transfusion of blood components in cancer patients and understand the amplitude of problems. There is also a need to consider validating preparation methods of blood components for so far ignored biological markers, such as microparticles and biological response modifiers. Meanwhile, blood component transfusions should be regarded as a personalized medicine, taking into careful consideration the status and specificities of the patient, rather than as a routine hospital procedure.

Comparative removal of solvent and detergent viral inactivating agents from human intravenous immunoglobulin G preparations using SDR HyperD and C18 sorbents.

The capacity of hydrophobic octadecyl (C18) and SDR HyperD materials to remove the combination of 1% (v/v) solvent (tri-n-butyl phosphate, TnBP) with 1% (v/v) nonionic detergents (Triton X-100 and Triton X-45) used for viral inactivation of plasma-derived polyvalent intravenous immunoglobulin G (IVIG) preparation has been evaluated. Efficient removal of TnBP (<10 ppm in IVIG preparation) was found at ratios of 0.5 g of C18/7 ml of IVIG and 0.22 g of dry SDR HyperD/7 ml of IVIG. Binding capacities of TnBP were greater than 140 mg/g of C18 and greater than 318 mg/g of dry SDR HyperD. Complete removal of Triton X-45 (<2 ppm) was obtained at ratios of 1g of C18/7 ml of IVIG and 0.44 g of dry SDR HyperD/7 ml of IVIG or above, corresponding to binding capacities in excess of 70 mg/g of C18 and in excess of 159 mg/g of dry SDR HyperD. Residual Triton X-100 was less than 30 ppm at a ratio of 4 g/14 ml of immunoglobulin G (IgG) for the C18 sorbent. Triton X-100 was less than 10 ppm when using SDR HyperD at a ratio of 0.66 g/7 ml of IgG, corresponding to a binding capacity of approximately 106 mg of Triton X-100/g of dry SDR HyperD. Good recoveries of IVIG were achieved in the effluent from both sorbents.

Impact of Triton X-100 on alpha 2-antiplasmin (SERPINF2) activity in solvent/detergent-treated plasma.

Large-pool solvent/detergent (SD) plasma for transfusion exhibits reduced alpha 2-antiplasmin (alpha2-AP; SERPINF2) functional activity. The reason for the loss of alpha2-AP has not been described and could be due to the SD incubation itself and/or to the processing steps implemented to remove the solvent and the detergent. We have studied alpha2-AP activity during six down-scale preparations of plasma virally-inactivated by 1% (v/v) TnBP combined with two different non-ionic detergents, either 1% Triton X-100 or 1% Triton X-45, at 31 degrees C for 4h. The SD-treated plasmas were then extracted with 7.5% (v/v) soybean oil, centrifuged at 3800 x g for 30 min, and subjected to hydrophobic interaction chromatography (HIC) to remove the SD agents. Control runs without TnBP and Triton were performed to evidence possible impacts of each process step on alpha2-AP activity. TnBP, Triton X-100, and Triton X-45 were measured at all stages of the processes to evaluate potential interferences with the alpha2-AP assay. Alpha 2-AP activity was about 10% that of starting plasma after 1% TnBP-1% Triton X-100 incubation and about 50% after oil extractions, centrifugation, and HIC. By contrast about 73% of the antiplasmin activity was found after the incubation with 1% TnBP and 1% Triton X-45, 88% after removal of the SD agents by oil extractions, 90% after centrifugation and 92% after HIC. The control runs performed without SD agents showed that the process steps did not affect the alpha2-AP activity. In conclusion, the agent altering alpha2-AP activity in SD-plasma is Triton X-100. The choice of detergents for the SD viral inactivation of therapeutic plasma fractions used in patients at risk of fibrinolysis should consider the impact on alpha2-AP activity.

A process for solvent/detergent treatment of plasma for transfusion at blood centers that use a disposable-bag system.

BACKGROUND: Solvent/detergent (S/D) inactivates enveloped viruses in plasma. The current technology requires a plasma fractionation facility and is applied to large plasma pools, which increases the cost and risks of exposure to S/D-resistant pathogens and lowers the content of protein S and alpha2-antiplasmin. Two S/D treatment procedures for single donations or minipools of plasma have been developed with a single-use bag system. STUDY DESIGN AND METHODS: Frozen plasma samples were thawed and treated in disposable bags with either 2 percent tri(n-butyl)phosphate (TnBP) at 37 degrees C or 1 percent TnBP and 1 percent Triton X-45 at 31 degrees C for 4 hours. Plasma samples were extracted three times with 7.5 percent sterile castor oil to remove TnBP and Triton X-45. The TnBP-treated plasma samples were further subjected to a clarifying centrifugation (3800 x g, 30 min). Final plasma samples were dispensed into individual bags and frozen at -30 degrees C. Plasma quality was assessed at each step of the procedures. RESULTS: Both processes yielded greater than 90 percent mean recovery of coagulation factors (clottable fibrinogen, von Willebrand factor, and factors VIII, V, VII, IX, X, and XI), anticoagulants (protein C, protein S), protease inhibitors (antithrombin, alpha2-antiplasmin), total protein, albumin, and immunoglobulins. Global coagulation tests of the treated plasma samples were normal. Final TnBP and Triton X-45 content was less than 10 and 50 ppm, respectively. CONCLUSION: S/D treatment of plasma can be performed in a closed-bag system under conditions that maintain plasma protein quality. The technology is simple, presents advantages over the industrial large-scale S/D plasma process, and could be performed in blood centers.