Leukocyte-depleted Blood Products Research Articles

Perioperative Transfusion of Leukocyte-depleted Blood Products in Contemporary Radical Cystectomy Cohort Does Not Adversely Impact Short-term Survival

To evaluate the effect of leukoreduced-only perioperative blood transfusion (PBT) and corresponding survival outcomes in a radical cystectomy cohort of patients. We analyzed data from 1026 patients who underwent radical cystectomy at our institution. PBT was defined as transfusion in the intraoperative or within the postoperative hospitalization period. Multivariable analyses using Cox proportional hazards were performed to measure the association between PBT, patient variables, and 3 primary end points: recurrence-free survival, disease-specific survival, and overall survival. Kaplan-Meier curves estimated survival times and were compared with log-rank test. Overall, of a total of 1026 patients, 341 (33.2%) received leukoreduced PBT. The median follow-up was 27.5 months. Transfused patients were more likely to be female, had higher estimated blood loss, lower preoperative hemoglobin, were more likely to have received neoadjuvant chemotherapy, or had undergone a continent urinary diversion. Higher pathologic tumor and nodal stage were observed more frequently in patients who received PBT. On multivariable analysis, PBT was not associated with worse recurrence-free survival, disease-specific survival, and overall survival (all P > .05). Kaplan-Meier curves did not show any significant differences (all P > .05) between the transfused and nontransfused groups. In addition, no differences were found in regard to timing of transfusion, that is, intraoperative vs postoperative, in distinct analysis. No significant association was found between leukoreduced PBT and worse survival outcomes at short-term follow-up in a contemporary cohort of cystectomy patients. Prospective long-term follow-up is warranted.

Perioperative transfusion of leukocyte depleted blood products in gastric cancer patients negatively influences oncologic outcome

The influence of perioperative transfusion (PT) on outcome following surgery for gastric cancer (GC) remains controversial, with randomized trials lacking and observational series confounded by patient risk factors. This analysis determines the association between reception of leukocyte-depleted blood products and post-operative survival for GC.Data from 610 patients who underwent curative surgery for GC in a German tertiary care clinic from 2001 to 2013 were included. Kaplan-Meier survival curves and Cox proportional hazards regression were applied to determine the association of PT and clinical and patient risk factors for overall and relapse-free survival. Propensity score analysis was performed to adjust for observational biases in reception of PT.Higher Union International Contre le Cancer/American Joint Committee on Cancer (UICC/AJCC)-stages (P <0.001), postoperative complications and severity according to the Clavien-Dindo (CD) classification (P <0.001), PT (P = 0.02), higher age (P <0.001), and neoadjuvant chemotherapy (P <0.001) were related to increased mortality rates. Higher UICC-stages (P <0.001), neoadjuvant chemotherapy (P <0.001), and type of surgery (P = 0.02) were independently associated with increased relapse rates. Patients were more likely to receive PT with higher age (P = 0.05), surgical extension to adjacent organs/structures (P = 0.002), tumor location (P = 0.003), and female gender (P = 0.03). In the adjusted propensity score weighted analysis, PT remained associated with an increased risk of death (hazard ratio (HR): 1.31, 95% CI: 1.01-1.69, P = 0.04).Because of the association of PT with negative influence on patient survival following resection for GC, risks from application of blood products should be weighed against the potential benefits.

Effect of transfusion, leukocyte-depleted blood product on onset of new septic shock and mortality in septic shock

A number of studies have observed decreased survival associated with transfusion. Leukocyte-mediated immunosuppression may contribute to postoperative infectious complications. There is evidence for a benefit with the use of leukocyte reduced transfusion, but it is unclear among septic shock patients. In Japan, leukocyte-depleted blood products have been used since 2007. We assessed the effect of transfusion and the efficacy of the use of leukocyte-depleted blood products for new onset of septic shock and mortality among patients with septic shock.

Recent advances in the prevention of CMV infection and disease after hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) remains an important pathogen in hematopoietic stem cell transplant (HCT) recipients in the current era of antiviral prophylaxis and preemptive therapy, despite the almost complete elimination of CMV disease during the first 3 months after transplantation. Pretransplant CMV serostatus of the donor and/or recipient remains an important risk factor for poor post-transplant outcome, especially in highly immunodeficient patients (e.g. recipients of ex vivo or in vivo T-cell depletion). Prevention of late CMV disease continues to be a challenge in selected high-risk populations, and indirect immunomodulatory effects of CMV (e.g. invasive bacterial and fungal infections) appear to contribute to the poor outcome. The risk of developing antiviral resistance remains low in most patients; however, in a setting of intense immunosuppression (e.g. after transplantation from a haploidentical donor) the incidence may be as high as 8%. Transfusion-transmitted CMV infection can be reduced by the provision of seronegative or leukocyte-depleted blood products; however, a small risk of 1-2% of CMV disease remains. Surveillance and preemptive therapy is effective in preventing transfusion-related CMV disease. The development of new drugs and immunologic strategies (adoptive transfer of CMV-specific T-cells and donor/recipient vaccination strategies) are important goals for the elimination of the negative impact of CMV in the HCT setting.

Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation. Significant progress has been made in the prevention of CMV disease over the past decade, but prevention of late CMV disease continues to be a challenge in selected high-risk populations. The pretransplantation CMV serostatus of the donor and/or recipient remains an important risk factor for posttransplantation outcome despite the use of antiviral prophylaxis and preemptive therapy; CMV-seropositive recipients of T cell-depleted grafts in particular continue to have a survival disadvantage compared with seronegative recipients with seronegative donors. The risk of developing antiviral drug resistance remains low in most patients; however, in a setting of intense immunosuppression (eg, after transplantation from a haploidentical donor), the incidence may be as high as 8%. Primary CMV infection via blood transfusion can be reduced by the provision of seronegative or leukocyte-depleted blood products; however, a small risk of 1% to 2% of CMV disease remains. Surveillance and preemptive therapy are effective in preventing the sequelae of transfusion-related CMV infection. Indirect immunomodulatory effects of CMV are increasingly recognized in hematopoietic stem cell transplant recipients. Strategies currently being investigated include long-term suppression of CMV with valganciclovir for the prevention of late CMV infection and disease, adoptive transfer of CMV-specific T cells, and donor and recipient vaccination strategies.

Generation of large numbers of human dendritic cells from whole blood passaged through leukocyte removal filters: an alternative to standard buffy coats

Many blood banks now use whole blood inline filtration to produce leukocyte-depleted blood products. As a result, a common source of large numbers of human dendritic cells (DC) for research purposes, namely standard buffy coats, has been lost. Therefore, we have adapted our conventional method for growing DC from CD14 + precursors in order to make use of these filter units. A dextran solution containing human serum albumin was used to flush back the filters. After pelleting, mononuclear cells were obtained by standard density gradient centrifugation (Lymphoprep™). To eliminate T cells, we used rosetting with sheep red blood cells. In addition to the classical PBMC, the cell population obtained after Lymphoprep™ centrifugation was found to contain high numbers of CD14 + granulocytes which could be depleted by separation on an additional Percoll gradient. At this stage, FACS analysis revealed a cell population that resembled the CD14 + monocyte-enriched population, obtained from traditional buffy coat preparations after Lymphoprep™ centrifugation and T cell elimination. Culture of the cells and the induction of maturation was identical to the previously described procedures, except that the culture time was reduced from 7 to 5 days and the maturation time from 3 to 2 days. Analyses of the major molecules indicative of DC maturation (CD83, CD86, CD208/DC-LAMP) and functional analyses of the T cell-stimulatory capacity of the DC population (using the MLR assay with normal peripheral T cells and naive T cells) revealed no major differences from buffy coat-derived DC preparations.

Leukocyte Filtration Does Not Affect Lymphocyte Subpopulations and NK Cell Function in Recipients of Blood Transfusions

Background and objectives: The possible immunosuppressive action of blood transfusion has aroused great interest recently, particularly with respect to its effects on tumor growth and recurrence rate of malignant disease. Materials and methods: The effect of blood transfusion on lymphocyte subpopulations and NK cell function preoperatively and 6 months postoperatively was studied in 129 patients treated with elective surgery for colorectal malignancy. Forty-two patients (33%) received blood transfusions, 21 of them randomly allocated to receive leukocyte-depleted blood products. Investigation was by means of conventional laboratory methods. Results: In 21 patients receiving a median of 3 units of non-leukocyte-depleted blood products (NLD), a significant reduction in CD4+ lymphocytes (44% vs. 40%, p < 0.01) occurred. In contrast, no significant changes in CD4+ lymphocytes were observed in the 21 patients transfused with leukocyte-depleted blood products (LD). However, with respect to lymphocyte subpopulations and NK cell function, differences between the NLD and LD groups were not significant. There was a marginal decrease in HLA-DR+ lymphocytes in the NLD patients without a history of previous transfusion. Conclusions: There seems to be no major change in lymphocyte subpopulations and NK cell function 6 months after blood transfusion. Thus we cannot confirm our previous findings of a reduced number of CD20+ cells after blood transfusion.

Leukocyte Filtration Does Not Affect Lymphocyte Subpopulations and NK Cell Function in Recipients of Blood Transfusions

The possible immunosuppressive action of blood transfusion has aroused great interest recently, particularly with respect to its effects on tumor growth and recurrence rate of malignant disease. The effect of blood transfusion on lymphocyte subpopulations and NK cell function preoperatively and 6 months postoperatively was studied in 129 patients treated with elective surgery for colorectal malignancy. Forty-two patients (33%) received blood transfusions, 21 of them randomly allocated to receive leukocyte-depleted blood products. Investigation was by means of conventional laboratory methods. In 21 patients receiving a median of 3 units of non-leukocyte-depleted blood products (NLD), a significant reduction in CD4+ lymphocytes (44% vs. 40%, p < 0.01) occurred. In contrast, no significant changes in CD4+ lymphocytes were observed in the 21 patients transfused with leukocyte-depleted blood products (LD). However, with respect to lymphocyte subpopulations and NK cell function, differences between the NLD and LD groups were not significant. There was a marginal decrease in HLA-DR+ lymphocytes in the NLD patients without a history of previous transfusion. There seems to be no major change in lymphocyte subpopulations and NK cell function 6 months after blood transfusion. Thus we cannot confirm our previous findings of a reduced number of CD20+ cells after blood transfusion.

HEPATITIS C VIRUS INFECTION AND ALLOGENEIC BONE MARROW TRANSPLANTATION

Serum antibodies to hepatitis C virus (HCV) were tested for inpatients undergoing allogeneic BMT to determine the risk of acquiring HCV infection and the role of HCV in posttransplant liver complications. The HCV seroconversion rate was evaluated according to the date of BMT and blood donor screening at the time. Anti-HCV antibodies (anti-HCV) were detected with a second-generation ELISA and confirmed with a second-generation radioimmunoblot assay. All patients received leukocyte-depleted blood products and most received apheresis platelet concentrates. One hundred twenty of 181 consecutive patients transplanted from January 1987 to December 1991 were anti-HCV-negative before BMT, had at least 6 months of follow-up, and were thus evaluated for the seroconversion rate. Before screening for non-A, non-B hepatitis, 14% of the patients seroconverted to HCV (0.44% per unit transfused). After introduction of screening for alanine aminotransferase and antibodies to hepatitis B core antigen the risk of seroconversion was 4% per patient (0.26% per unit). When, in addition, blood was screened for anti-HCV the risk fell to 1.6% (0.03% per unit). Positive anti-HCV status before and after BMT was not predictive of veno-occlusive disease, liver graft-versus-host disease (GVHD), or death due to liver dysfunction. In contrast, the risk of chronic hepatitis was significantly increased.

白血球除去血液製剤に残存する微量白血球の測定 全自動型フローサイトメターの開発

白血球除去血液製剤に残存する微量白血球の測定 全自動型フローサイトメターの開発

Contrôles de performance de la filtration

The technique of filtration which has constantly been improved over past years makes it possible to obtain highly pure blood products (the rate of leukocyte depletion can reach 3 to 5 log). Several study groups (BEST, PSL) and international committees of experts have defined a number of standards with which leukocyte depleted blood products must comply. Assessment of filtration procedures is thus made necessary, it applies to the different steps of the filtration procedure: preparation techniques of red cell or platelet suspension, priming and rinsing of the filter. Likewise a number of parameters have to be checked: filtration time, temperature, age of suspensions. Moreover quality control procedures must be implemented, using adapted and validated measuring methods (Nageotte hemacytometer, for instance). The parameters to be monitored include the number of residual leukocytes, (mean value: 1 x 10(6), i.e. about 4 WBCs/microliters), and the rate of hemoglobin or platelet recovery. Any new filtering equipment or material must satisfy strict requirements and standards including clinically acceptable limits as part of the same quality approach. Validation, in this case, consists in determining the maximal leukocyte content which the filter can absorb (capacity) and the average rate of leukocyte removal (efficacy). The constant monitoring of filtration performance contributes to improving the quality of red blood cell or platelet suspensions and thus meet clinicians' requirements for their patients.

An Animal Model of Allogeneic Donor Platelet Refractoriness: The Effect of the Time of Leukodepletion

Approximately 50% of multi-transfused individuals become refractory to random donor platelets. Recent clinical data suggest that those patients receiving leukocyte-depleted blood products are less likely to become refractory to random donor platelets than recipients of non-leukocyte-depleted products. Leukocyte depletion can be performed immediately after collection of a unit of whole blood before its storage (prestorage leukodepletion) or just before the transfusion of the blood product to a recipient, after its storage (poststorage leukodepletion). However, the most appropriate time for the leukodepletion of blood products has not been established. The present study was undertaken to establish an animal model of allogeneic platelet refractoriness, and to compare the effect of prestorage and poststorage leukodepletion on the frequency of refractoriness to allogeneic donor platelets. In this model, two strains of rabbits were used: California Black rabbits were used as blood donors, while New Zealand White rabbits were used as recipients. Eight weekly infusions of nonleukodepleted allogeneic fresh blood resulted in an allogeneic platelet refractory rate of 91.2% (31/34). The prestorage leukodepletion of the donor blood was associated with a significantly higher allogeneic platelet survival and lower refractory rate (33.3%) to allogeneic platelets than poststorage leukodepletion (66.7%). Furthermore, the data suggest that cell-free plasma products are capable of inducing refractoriness to allogeneic donor platelets; the stored plasma having a greater likelihood of inducing such refractoriness than fresh plasma. Thus, these data provide evidence that the prestorage leukodepletion of allogeneic donor blood is associated with a lower frequency of refractoriness and better allogeneic platelet survival than poststorage leukodepletion.

An animal model of allogeneic donor platelet refractoriness: the effect of the time of leukodepletion

Approximately 50% of multi-transfused individuals become refractory to random donor platelets. Recent clinical data suggest that those patients receiving leukocyte-depleted blood products are less likely to become refractory to random donor platelets than recipients of non- leukocyte-depleted products. Leukocyte depletion can be performed immediately after collection of a unit of whole blood before its storage (prestorage leukodepletion) or just before the transfusion of the blood product to a recipient, after its storage (poststorage leukodepletion). However, the most appropriate time for the leukodepletion of blood products has not been established. The present study was undertaken to establish an animal model of allogeneic platelet refractoriness, and to compare the effect of prestorage and poststorage leukodepletion on the frequency of refractoriness to allogeneic donor platelets. In this model, two strains of rabbits were used: California Black rabbits were used as blood donors, while New Zealand White rabbits were used as recipients. Eight weekly infusions of nonleukodepleted allogeneic fresh blood resulted in an allogeneic platelet refractory rate of 91.2% (31/34). The prestorage leukodepletion of the donor blood was associated with a significantly higher allogeneic platelet survival and lower refractory rate (33.3%) to allogeneic platelets than poststorage leukodepletion (66.7%). Furthermore, the data suggest that cell-free plasma products are capable of inducing refractoriness to allogeneic donor platelets; the stored plasma having a greater likelihood of inducing such refractoriness than fresh plasma. Thus, these data provide evidence that the prestorage leukodepletion of allogeneic donor blood is associated with a lower frequency of refractoriness and better allogeneic platelet survival than poststorage leukodepletion.

ナジョットチェンバー・ハウザーチェンバーを用いた白血球除去血液製剤中の残存白血球数の測定

ナジョットチェンバー・ハウザーチェンバーを用いた白血球除去血液製剤中の残存白血球数の測定

Introduction: Leukocyte-Depleted Blood Products

Introduction: Leukocyte-Depleted Blood Products

Early detection of active cytomegalovirus (CMV) infection after heart and kidney transplantation by testing for immediate early antigenemia and influence of cellular immunity on the occurrence of CMV infection

To determine the incidence of active cytomegalovirus (CMV) infection after organ transplantation and its relationship with the immune system, 55 renal and 14 cardiac transplant recipients were closely monitored for active CMV infection (expression of CMV immediate early antigen in granulocytes--antigenemia--and positive cultures) and immune parameters. All 19 CMV-seronegative recipients with seronegative donors remained seronegative, showing that no CMV transmission occurred by leukocyte-depleted blood products. Primary CMV infection occurred in 4 of 11 (36%) patients with positive donors and was symptomatic in 1 (9%) patient. Active CMV infection was found in 29 of 39 (74%) seropositive patients and was symptomatic in 3 (8%) patients. CMV antigenemia was always the first indication of active CMV infection (antigenemia, on average, at day 45 +/- 15; immunoglobulin G rise at day 71 +/- 36; and positive cultures at day 70 +/- 17). Cellular immunity, as measured by lymphocyte proliferation (LPT), proved to be of importance in the prevention of active CMV infection, as 14 of 15 patients with negative LPT obtained active CMV infections with antigenemia and positive cultures, whereas 1 of 10 patients with positive LPT did so (P less than 0.0001).

Stratégie transfusionnelle pour les malades en aplasie thérapeutique: Expérience de l'hôpital Henri Mondor à propos de 2 protocoles successifs

Retrospective analysis of two transfusion protocols applied in our institution to the bone marrow transplanted patients was conducted. Granulocyte transfusions should be only proposed as a therapeutic treatment to patients with severe well documented bacterial infection resistant to an adapted antibiotherapy. Leukocyte-depleted blood products reduce the incidence of HLA-immunization but do not influence the frequency of CMV infections. Random single donor platelet concentrates (obtained by cytapheresis) could decrease the incidence of polyspecific HLA-antibodies in comparison with the use of random standard platelet concentrates. The best transfusion protocol should associate leukocyte-depleted blood products with transfusion of prophylactic single donor platelet concentrates. In our institution, this protocol is less expensive than the protocol with prophylactic white blood cell transfusions and has the same cost than other protocols using standard blood products.