Evaluation of leukocyte depletion of packed red blood cell units and impact on clinically observed transfusion reactions.

Introduction: The aim of this retrospective study was to determine whether there is an association between leukoreduction of packed red blood cell (pRBC) units and reduction of clinically observed transfusion reactions (TR), particularly febrile non-haemolytic transfusion reactions (FNHTR), and better outcomes in dogs. Secondary aims were to evaluate the effects of other factors suspected to influence transfusion reaction frequency or survival, including crossmatching, use of immunosuppressive drugs, and age and number of the blood products being administered. Materials and methods: Medical data on dogs transfused with leukocyte-reduced (LR) and non-leukocyte-reduced (N-LR) pRBC units at the Animal Hospital Zürich, University of Zürich, Switzerland between January 1, 2007, and December 17, 2018 were searched. Before 2014, only N-LR blood were transfused. After 2014, both LR and N-LR blood were available. Results: A total of 339 canine patients were transfused with 413 pRBC units; 30.5% (126/413) were LR units and 69.5% (287/413) were N-LR. Data collected from medical records was analyzed using univariate and multivariate logistic regression. In the present study, TR occurred in 19.8% of pRBC units (25/126) with LR and in 17.7% (51/287) of pRBC with N-LR; p > 0.05. FNHTR occurred in 6.3% of pRBC units (8/126) with LR and in 4.5% (13/287) of those with N-LR; p > 0.05. There was no correlation between the occurrence of TR and discharge from hospital (p > 0.05). Crossmatching, immunosuppressive therapy, and age of the blood product were not associated with the frequency of TR; p > 0.05 for all. The duration of survival days was not related to the number of transfusions dogs received. Discussion: In the present study, the leukocyte-depletion of transfused pRBC units was not associated with fewer TR nor to fewer FNHTR compared to N-LR units. Discharge of dogs from hospital was not dependent on the occurrence of TR.

Investigation of the patients with recurrent acute transfusion reactions: A single tertiary medical centre experience.

OBJECTIVE: To assess the spectrum of patients who developed recurrent acute transfusion reactions (TRs) and to characterize these recurrent TRs. METHODS: This retrospective study included patients who developed ≥2 acute TRs between April 2017 and March 2020 in a tertiary medical centre. RESULTS: Among 216 TRs that occurred after 2024 transfusions in 87 patients, 66 (75.9%) patients reported a history of transfusions before the first TR and 70 (80.5%) patients received further transfusions after the last TR; with the same type of TR and reaction to the same type of blood product observed in 59 (67.8%) patients and 56 (64.4%) patients, respectively. TRs were most commonly associated with packed red blood cell (PRBC) transfusions and a febrile non-haemolytic transfusion reaction (FNHTR) was the most common type of TR. However, leukocyte reduced (LR) PRBCs were less common than LR platelets among transfusions with TR (22.7% [27/119] versus 75.0% [57/76], respectively) and premedication was prescribed before 196 of 216 (90.7%) transfusions with TR. CONCLUSION: Most patients with recurrent TRs received repeated transfusions in addition to transfusions with TR. Instead of considering premedication, an increase in the use of LR might be the strategy to reduce the recurrence of TR.

Leukocyte Reduction Filters Are Reliable and Economic Source for Natural Killer Cell Preparation.

Background: An issue that hinders researchers' access to Natural Killer (NK) cells is their low proportion in peripheral blood leukocytes. This issue is currently addressed by methods involving a series of differentiation and expansions that are time-consuming and expensive. Objective: We have investigated whether the used leukocyte reduction filters, a by-product in the blood transfusion practice that currently is considered waste, can be utilized as a source of the NK cells. Methods: Following the blood donation of 46 donors based on the Iranian Blood Transfusion Organization's protocols, a sample of peripheral blood of each donor and the leukocyte reduction filter used in their donation procedure have been obtained. The entrapped cells were flushed back from the leukocyte reduction filters. Both groups of samples were analyzed using an automatic hematological analyzer. NK cell isolation was done by the MACS negative selection method. The samples have been comparatively analyzed utilizing flow cytometry data of NK cells' subpopulation compositions, viability, degranulation patterns, and cytotoxic capacity against the K562 cell line. Results: Every major leukocyte population was abundant in the samples extracted from the used leukocyte reduction filters. The NK cells extracted from leukocyte reduction filters did not show any statistically meaningful differences (P<0.5) from peripheral blood samples in terms of subpopulation composition, viability, degranulation potency, and cytotoxic capacity. Conclusion: Used leukocyte reduction filters can be considered an economic, easy to obtain, and robust source of abundant research-grade NK cells.

Common Data Model-based Analysis of Selective Leukoreduction Protocol Compliance at Three Hospitals.

Background: The selective leukoreduction protocol (SLP) is limited in that patients who require it can be overlooked. We estimated SLP compliance (SLPC) using the Observational Medical Outcomes Partnership common data model (CDM). Methods: Patients were classified into eight groups: pre- and post-hematology disease (A and B), pre- and post-solid organ transplantation (C and D), solid cancer (E), immunodeficiency (F), anticancer therapy (G), and cardiovascular surgery (H). We examined the red blood cell (RBC) transfusion history from three hospital datasets comprising approximately three million patients over 20 years using CDM-based analysis. SLPC was calculated as the percentage of patients who received only leukoreduced RBCs in total patients transfused RBCs. Results: In total, 166,641 patients from three hospitals were enrolled in this study. From 2001 to 2021, SLPC in all groups, except H, tended to increase, although there were differences among the hospitals. Based on the most recent values (2017-2021), the SLPC in groups A, B, D, and G was maintained at ≥75% until 1,095 days before or after diagnosis or treatment. Groups E, F, and H had < 50% SLPC one day after diagnosis and treatment. Conclusions: CDM analysis supports the review of large datasets for SLPC evaluation. Although SLPC tended to improve in most patient groups, additional education and monitoring are needed for groups that continue to show low SLPC.

A method based on plateletpheresis to obtain functional platelet, CD3+ and CD14+ matched populations for research immunological studies.

BACKGROUND: In previous studies with peripheral blood cells, platelet factors were found to be associated with severe allergic phenotypes. A reliable method yielding highly concentrated and pure platelet samples is usually not available for immunological studies. Plateletpheresis is widely used in the clinics for donation purposes. In this study, we designed a protocol based on plateletpheresis to obtain Platelet-Rich Plasma (PRP), Platelet-Poor Plasma (PPP) as well as CD3+ and CD14+ cells matched samples from a waste plateletpheresis product for immunological studies. METHODS: Twenty-seven subjects were voluntarily subjected to plateletpheresis. PRP, PPP and blood cell concentrate contained in a leukocyte reduction system chamber (LRSC) were obtained in this process. CD3+ and CD14+ cells were isolated from the LRSC by density-gradient centrifugation and positive magnetic bead isolation. RNA was isolated from PRP, CD3+ and CD14+ cell samples and used for transcriptomic studies by Affymetrix. PRP and PPP samples were used for platelet protein quantification by multiplex assays. RESULTS: A reliable high yield method to obtain matched samples of PRP, PPP, CD3+ and CD14+ from a single donor for RNA and protein analyses has been designed. The RNA quality indicators (RQI) routinely used for other cell types were not suitable for platelet RNA characterization. Despite this, the platelet RNA was valid for transcriptomic studies by Affymetrix, as platelet transcripts obtained in our previous studies were confirmed in PRP samples. Platelet samples were enriched in platelet factors as determined in protein multiplex analysis. CONCLUSIONS: We have developed a method that yields not only high content and pure platelet samples from a single donor but also CD3+ and CD14+ matched samples that can be used for RNA and protein analyses in immunological studies.

Leukocyte reduction filters as an alternative source of peripheral blood leukocytes for research

ABSTRACT Introduction: Peripheral blood leukocytes are a suitable cell model for science research. However, blood samples from healthy volunteers are limited in volume and difficult to obtain due to the complexity of volunteer recruitment. Objective: Therefore, it is urgent to find an alternative source of peripheral blood leukocytes. Method: One of the possibilities is the use of leukocyte reduction filters (LRFs) in blood banks that is used for preparation of leukoreduced blood products. More than 90% of the leukocytes are trapped in the leukofilters allowing the desired blood product to pass through. Results: It has been reported that the biological function of leukocytes collected from the filters are no different from those isolated from buffy coats, leukapheresis products and whole blood (WB) cells. Moreover, LRFs are waste products that are discarded after leukoreduction. Conclusion: Thus, leukofilters represent an economic source of human cell populations that can be used for a variety of investigative purposes, with no cost. In the present study, we reviewed the different usage of LRFs in the research, clinical and commercial applications.

Leukocyte kinetics during the first cycle of chemotherapy predicts the outcome of patients with metastatic colorectal cancer and previous resection of the primary tumor.

BACKGROUND: Many reports suggest more activity of cytotoxic chemotherapy among patients with metastatic colorectal cancer (mCRC) who experience neutropenia, but it is not clear whether this finding is related to drug effect alone. The aim of the study is to identify the characteristics of patients whose peripheral blood cell kinetics (PBCK) is related to the outcome. METHODS: The study is a retrospective analysis of patients with mCRC who had received first-line chemotherapy at Sanremo hospital from 2010 to 2015, evaluating seventeen baseline variables, six related to systemic inflammatory response activation (SIRA), and six to peripheral blood cell kinetics after one cycle. The relationship of peripheral blood cell kinetics variables was evaluated by tumor location, SIRA, and timing of metastases. RESULTS: Among 203 eligible patients, only four variables were able to independently predict survival (age, CA 19-9, number of drugs, chemotherapy-induced leukopenia after the first cycle or CIL-1). After stratification by tumor location or by SIRA, no relationship of PBCK variables with prognosis was present. On the contrary, after stratification by timing of metastasis, the prognostic role of CIL-1 was evident among patients with metachronous metastases, particularly among those with low SIRA and colon tumors, whereas the leukocyte reduction after the first cycle (WR) predicted longer survival of patients with synchronous metastases and a previous resection of the primary tumor (PTR). CONCLUSIONS: Absolute leukocyte reduction (CIL-1) predicts a better OS of patients with metachronous metastases, whereas relative leukocyte reduction (WR) could be prognostic among patients with synchronous metastases who have received PTR.

Leukocyte reduction filters as an alternative source of peripheral blood leukocytes for research.

INTRODUCTION: Peripheral blood leukocytes are a suitable cell model for science research. However, blood samples from healthy volunteers are limited in volume and difficult to obtain due to the complexity of volunteer recruitment. OBJECTIVE: Therefore, it is urgent to find an alternative source of peripheral blood leukocytes. METHOD: One of the possibilities is the use of leukocyte reduction filters (LRFs) in blood banks that is used for preparation of leukoreduced blood products. More than 90% of the leukocytes are trapped in the leukofilters allowing the desired blood product to pass through. RESULTS: It has been reported that the biological function of leukocytes collected from the filters are no different from those isolated from buffy coats, leukapheresis products and whole blood (WB) cells. Moreover, LRFs are waste products that are discarded after leukoreduction. CONCLUSION: Thus, leukofilters represent an economic source of human cell populations that can be used for a variety of investigative purposes, with no cost. In the present study, we reviewed the different usage of LRFs in the research, clinical and commercial applications.

Allogeneic Leukocyte-Reduced Red Blood Cell Transfusion Is Associated with Postoperative Infectious Complications and Cancer Recurrence after Colon Cancer Resection.

BACKGROUND/AIMS: Transfusion rates in colon cancer surgery are traditionally very high. Allogeneic red blood cell (RBC) transfusions are reported to induce immunomodulation that contributes to infectious morbidity and adverse oncologic outcomes. In an effort to attenuate these effects, the study institution implemented a universal leukocyte reduction protocol. The purpose of this study was to examine the impact of leukocyte-reduced (LR) transfusions on postoperative infectious complications, recurrence-free survival, and overall survival (OS). METHODS: In a retrospective study, patients with stage I-III adenocarcinoma of the colon from 2003 to 2010 who underwent elective resection were studied. The primary outcome measures were postoperative infectious complications and recurrence-free and OS in patients that received a transfusion. Bivariate and multivariable regression analyses were performed for each endpoint. RESULTS: Of 294 patients, 66 (22%) received a LR RBC transfusion. After adjustment, transfusion of LR RBCs was found to be independently associated with increased infectious complications (OR 3.10, 95% CI 1.24-7.73), increased odds of cancer recurrence (hazard ratio [HR] 3.74, 95% CI 1.94-7.21), and reduced OS when ≥3 units were administered (HR 2.24, 95% CI 1.12-4.48). CONCLUSION: Transfusion of LR RBCs is associated with an increased risk of infectious complications and worsened survival after elective surgery for colon cancer, irrespective of leukocyte reduction.

Risk of cytomegalovirus transmission by blood products after solid organ transplantation.

Cytomegalovirus (CMV) infection and CMV disease are significant contributors to increased morbidity, mortality, and cost for immunocompromised solid organ transplant recipients. Although the most significant risk for CMV transmission is the CMV serological status of the transplant donor and recipient, exposure to blood products is another potential risk factor. Before the era of leukocyte reduction, CMV seronegative products were issued to reduce the risk of CMV transmission, thus rendering the products CMV safe. This approach requires maintenance of two inventories of blood products and continuous donor testing. Leukocyte-reduced cellular transfusion products are also considered CMV safe and are essentially universally available. To minimize the risk of CMV infection in transplant recipients, strategies include use of seronegative blood products or prestorage leukocyte reduction. However, no recent randomized prospective controlled trial directly compares the two CMV safety approaches for transplant recipients. Hence, current policy relies on historic trials and more recent observational studies. As a consequence, though generally considered equivalent approaches, preferred practice varies between centers. This review provides guidance to inform an acceptable practice approach.

Effects of irradiation and leukoreduction on down-regulation of CXCL-8 and storage lesion in stored canine whole blood.

White blood cells (WBCs) and storage period are the main factors of transfusion reactions. In the present study, cytokine/chemokine concentrations after leukoreduction (LR) and irradiation (IR) in stored canine whole blood were measured. Red blood cell storage lesion caused by IR and LR were also compared. Blood samples from 10 healthy Beagles were divided into four groups (no treatment, LR-, IR-, and LR + IR-treated). Leukocytes were removed by filtration in the LR group and gamma radiation (25 Gy) was applied in the IR group. Immunologic factors (WBCs, interleukin-6 [IL-6], C-X-C motif chemokine ligand 8 [CXCL-8], and tumor necrosis factor-alpha) and storage lesion factors (blood pH, potassium, and hemolysis) were evaluated on storage days 0, 7, 14, 21, and 28. Compared to the treated groups, IL-6 and CXCL-8 concentrations during storage were significantly higher in the control (no treatment) group. LR did not show changes in cytokine/chemokine concentrations, and storage lesion presence was relatively mild. IR significantly increased CXCL-8 after 14 days of storage, but IR of leukoreduced blood did not increase CXCL-8 during 28 days of storage. Storage lesions such as hemolysis, increased potassium, and low pH were observed 7 days after IR and storage of blood, regardless of LR. IR of leukoreduced blood is beneficial to avoid immune reactions; however, storage lesions should be considered upon storage.

Therapeutic leukocyte reduction for acute and chronic myeloid leukemias: A 4-year experience from an oncology center in India.

INTRODUCTION: Hyperleukocytosis (HL) and leukostasis seen in myeloid leukemias are a medical emergency. We present a case series of ten such patients in a 4-year period. Sixteen therapeutic leukocyte reduction (TLR) were done in ten cases along with other supportive measures. The American Society for Apheresis supports the routine implementation of TLR in cases of HL secondary to myeloid leukemias with signs of leukostasis. MATERIALS AND METHODS: The procedures were performed on the intermittent flow cell separator after discussion with the treating physician about patient's condition. Clinical, demographic, analytical, and technical variables were reviewed retrospectively and the patients were followed up at the end of 4 years. Descriptive analysis was performed for all variables, and relationships between quantitative variables and categorical variables were determined by applying the Student's t-test. RESULTS: The mean age of presentation was 34 years. Priapism was the most common symptom followed by respiratory distress and neurological disturbances. After an average of 1.6 TLR procedures, the mean leukocyte count reduction achieved was 39.9% along with symptomatic relief. The mean survival at 4-year follow-up was 12.8 months and the overall mortality was 20%. Acute myeloid leukemia patients presented with lower mean platelet counts compared to chronic myeloid leukemia patients; however, the platelet loss in the final product was minimized. CONCLUSION: TLR is a safe and effective therapy for leukoreduction in hematological malignancies in our experience.

Optimization of pure platelet-rich plasma preparation: A comparative study of pure platelet-rich plasma obtained using different centrifugal conditions in a single-donor model.

While it has been proved that centrifugal conditions for pure platelet-rich plasma (P-PRP) preparation influence the cellular composition of P-PRP obtained, the optimal centrifugal conditions to prepare P-PRP have not yet been identified. In the present study, platelet-containing plasma (PCP) was prepared with the first-spin of different double-spin methods and P-PRP was prepared with different double-spin methods. Whole-blood analysis was performed to evaluate the cellular composition of PCP and P-PRP. The basal and ADP-induced CD62P expression rates of platelets were assessed by flow cytometry to evaluate the function of platelets in PCP and P-PRP. Enzyme-linked immune sorbent assay was performed to quantify interleukin-1ß, tumor necrosis factor-α, platelet-derived growth factor AB and transforming growth factor ß1 concentrations of PCP and P-PRP. Correlations between the cellular characteristics and cytokine concentrations of P-PRP were analyzed by Pearson correlation analysis. Effects of P-PRP on the proliferation, survival and migration of human bone marrow-derived mesenchymal stem cells and human articular chondrocytes were evaluated by a Cell Counting Kit-8 assay, live/dead staining and Transwell assay, respectively. The results showed that centrifugation at 160 × g for 10 min and 250 × g for 15 min successively captured and concentrated platelets and growth factors significantly more efficiently with preservation of platelet function compared with other conditions (P<0.05). The correlation analysis showed that the similar leukocyte concentrations and leukocyte-reducing efficiencies resulted in similar pro-inflammatory cytokine concentrations in P-PRP (P>0.05) and the maximization of platelet concentration, platelet enrichment factor, platelet capture efficiency and platelet function resulted in the maximization of growth factor concentrations in P-PRP obtained using the optimal conditions (P<0.05). Compared with P-PRP obtained under other conditions, P-PRP obtained under the optimal conditions significantly promoted the proliferation and migration of cells (P<0.05) and did not alter cell survival (P>0.05). Therefore, centrifugation at 160 × g for 10 min and 250 × g for 15 min successively with removal of the buffy coat as a crucial step may provide an optimal preparation system of P-PRP for clinical application.

Balance Between the Proinflammatory and Anti-Inflammatory Immune Responses with Blood Transfusion in Sepsis.

Blood product transfusion may exacerbate the initial immunosuppressive response of sepsis. Nurses and other patient care providers must be diligent in recognizing and managing a worsening immune status, using flow cytometry to monitor patients' immune status. This type of monitoring may be instrumental in reducing morbidity and mortality in persons with sepsis. This article discusses the recent literature on the associated inflammatory responses that occur with blood transfusion and provides an analysis of alterations in key inflammatory pathways in response to transfusion in a sepsis population.

Regulation of the lysophosphatidylserine and sphingosine 1-phosphate levels in autologous whole blood by the pre-storage leukocyte reduction.

BACKGROUND AND OBJECTIVES: The effect of leukoreduction and storage periods on the accumulation of bioactive lysophospholipids and substances in human autologous blood (AB units) has not been fully investigated. MATERIALS AND METHODS: The accumulation of bioactive lysophospholipids such as sphingosine 1-phosphate (S1P) and lysophosphatidylserine (LysoPS) in AB units during the storage was investigated. The time-dependent changes and the effect of the filtration in pre-storage leuckoreduction (LR) and unmodified samples derived from 46 AB units were analysed. Additionally, the changes of lysophospholipids and platelet releasate, namely ß-thromboglobulin (ß-TG), induced by exposure of whole blood (WB) or platelet-rich plasma (PRP) to the filter material were analysed. RESULTS: LysoPS, but not S1P levels, time-dependently and significantly increased in both unmodified and LR samples. LysoPS significantly decreased in LR compared with unmodified samples, whereas S1P increased in LR compared with unmodified samples. In addition, exposure of WB and/or PRP to the filter material in vitro resulted in increased levels of S1P, LysoPS and ß-TG. CONCLUSIONS: LR effectively reduced the accumulation of LysoPS in AB units. On the other hand, it increased concentrations of S1P due to platelet activation by exposure to the filter material. These suggest that increases of S1P levels in LR and LysoPS in the unmodified samples were mainly caused by the leukocytes and/or platelets and that LR was effective in inhibiting the accumulation of LysoPS.

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

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.

Transfusion in CMV seronegative T-depleted allogeneic stem cell transplant recipients with CMV-unselected blood components results in zero CMV transmissions in the era of universal leukocyte reduction: a U.K. dual centre experience.

OBJECTIVES: To establish rates of cytomegalovirus (CMV) transmission with use of CMV-unselected (CMV-U), leukocyte-reduced blood components transfused to CMV-seronegative patient/CMV-seronegative donor (CMV neg/neg) allogeneic stem cell transplantation (SCT) recipients including those receiving T-depleted grafts. BACKGROUND: CMV infection remains a major cause of morbidity following SCT. CMV-seronegative SCT recipients are particularly at risk of transfusion transmitted CMV (TT-CMV) and until recently they have received blood components from CMV-seronegative donors with significant resource implications. Although leukocyte reduction of blood components is reported to minimise risk of TT-CMV, its efficacy in high-risk situations, such as in T-depleted transplant recipients, is unknown. METHODS: We retrospectively analysed the incidence of TT-CMV in CMV neg/neg allogeneic SCT recipients transfused with CMV-U, leukocyte-reduced blood components in two transplantation centres in the UK. Patients were monitored for CMV infection by weekly CMV polymerase chain reaction testing. Leukocyte reduction of blood components was in accordance with current UK standards. RESULTS: Among 76 patients, including 59 receiving in vivo T-depletion, no episodes of CMV infection were detected. Patients were transfused with 1442 CMV-unselected, leukocyte-reduced components, equating to 1862 donor exposures. CONCLUSIONS: Our findings confirm the safety of leukocyte reduction as a strategy in preventing TT-CMV in high-risk allogeneic SCT recipients.

Introduction of universal prestorage leukodepletion of blood components, and outcomes in transfused cardiac surgery patients.

OBJECTIVE: To assess whether introduction of universal leukodepletion (ULD) of red blood cells (RBCs) for transfusion was associated with improvements in cardiac surgery patient outcomes. METHODS: Retrospective study (2005-2010) conducted at 6 institutions. Associations between leukodepletion and outcomes of mortality, infection, and acute kidney injury (AKI) were modeled by logistic regression, and intensive care unit length of stay (LOS) in survivors was explored using linear regression. To examine trends over time, odds ratios (ORs) for outcomes of transfused were compared with nontransfused patients, including a comparison with nontransfused patients who were selected based on propensity score for RBC transfusion. RESULTS: We studied 14,980 patients, of whom 8857 (59%) had surgery pre-ULD. Transfusions of RBCs were made in 3799 (43%) pre-ULD, and 2525 (41%) post-ULD. Administration of exclusively leukodepleted, versus exclusively nonleukodepleted, RBCs was associated with lower incidence of AKI (adjusted OR 0.80, 95% confidence interval [CI] 0.65-0.98, P = .035), but no difference in mortality or infection. For post-ULD patients, no difference was found in mortality (OR 0.96, 95% CI 0.76-1.22, P = .76) or infection (OR 0.91, 95% CI 0.79-1.03, P = .161); however, AKI was reduced (OR 0.79 95% CI 0.68-0.92, P = .003). However, ORs for post-ULD outcomes were not significantly different in nontransfused, versus transfused, patients. Furthermore, those who received exclusively nonleukodepleted RBCs were more likely to have surgery post-ULD. CONCLUSIONS: Universal leukodepletion was not associated with reduced mortality or infection in transfused cardiac surgery patients. An association was found between ULD and reduced AKI; however, this reduction was not significantly different from that seen in nontransfused patients, and other changes in care most likely explain such changes in renal outcomes.

TCR-mediated functions are enhanced in activated peripheral blood T cells isolated from leucocyte reduction systems.

Buffy coats are the most common method for the acquisition of activated primary human T cells for research or clinical applications, but recently leukocyte reduction system (LRS) cones have emerged as a viable source for these cells. In this study, we determined if activated human T cells derived from buffy coats or LRS cones had different functionality. No changes in the expression of surface receptors were observed except for a significant increase in CD44 expression on T cells isolated from LRS cones. LRS cone-derived T cells trended towards higher receptor-mediated cytokine production and had significantly increased donor-to-donor variability in IFN-γ production. TCR-induced ERK1/ERK2 and AKT phosphorylation was also increased in T cells isolated from LRS cones. In conclusion, LRS cones are an excellent source of T cells for clinical and research applications, but these cells have subtle functional differences from T cells isolated using standard buffy coats.

Supportive transfusion therapy in cancer patients with acquired defects of hemostasis.

Bleeding occurs in approximately 10% of patients with cancer: supportive transfusion therapy with Platelets Concentrates (PC), Fresh Frozen Plasma (FFP) and plasma-derived or recombinant concentrates is often required for the cessation and prevention of the bleeding episodes. The most frequent causes of bleeding in cancer is thrombocytopenia followed by liver insufficiency with or without vitamin K deficiency, disseminated intravascular coagulation (DIC) and the inappropriate or excessive use of anticoagulants. Other acquired hemostatic defects such as acquired hemophilia (AHA) and acquired von Willebrand syndrome (AVWS) are rare but they can be life-threatening. Thrombocytopenia in cancer patients may be the consequence of marrow invasion, chemotherapy or platelet auto-antibodies; patients with severe hypoproliferative thrombocytopenia, must be treated with PC and carefully followed to assess refractoriness to PC. The management of the other acquired defects of hemostasis usually requires the use of FFP and specific plasma-derived or recombinant concentrates. PC, FFP and plasma-derived concentrates can induce complications and/or adverse events in cancer patients: these include mainly allergic (ALR) or anaphylactic reactions (ANR), Transfusion-Associated Graft-Versus-Host Disease (TA-GVHD), Trasfusion-transmitted bacteriemia (TTB), Transfusion-Related Acute Lung Injury (TRALI), Acute Hemolytic Transfusion Reactions (AHTR), Febrile Non Hemolytic Transfusion Reactions (FNHTR). Therefore, modifications such as leukocyte-reduction and irradiation of the blood components to be transfused in cancer patients are recommended to reduce the risk of these complications.