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Granulocyte transfusions continue to be used in clinical practice, predominantly for treatment of refractory infection in the setting of severe neutropenia. There is biological plausibility for effectiveness in these patients with deficiencies of neutrophils, either as a consequence of disease or treatment. However, there is a chequered history of conducting and completing interventional trials to define optimal use, and many uncertainties remain regarding schedule and dose. Practice and clinical studies are severely limited by the short shelf life and viability of current products, which often restricts the timely access to granulocyte transfusions. In the future, methods are needed to optimise donor-derived granulocyte products. Options include use of manufactured neutrophils, expanded and engineered from stem cells. Further possibilities include manipulation of neutrophils to enhance their function and/or longevity. Granulocyte transfusions contain a heterogeneous mix of cells, and there is additional interest in how these transfusions may have immunomodulatory effects, including for potential uses as adjuncts for anti-cancer effects., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10-1.59) × 10 9 /kg. The median neutrophil increment one day after GTX was 515 (range, -6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 10 9 /kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection., Competing Interests: Declaration of interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: It remains controversial whether granulocyte transfusions as a supportive treatment improve survival in patients with febrile neutropenia or granulocyte dysfunctions. We describe survival rates subsequent to granulocyte transfusions in pediatric and adults patients treated at a major blood center in Brazil., Material and Methods: We retrospectively reviewed the clinical charts of pediatric and adult patients treated with granulocyte transfusions at our institution from January 2000 to October 2019. We assessed demographic characteristics, clinical features, indications for transfusion, units transfused, dose of granulocytes administered and survival rates 30 and 100 days after the initial transfusion., Results: We identified 64 pediatric and 67 adult patients treated with 262 granulocyte transfusions. An optimal dose (> 0.6 × 10 9 granulocytes per kilogram per transfused unit) was available for transfusion in 80.4 % of pediatric patients but in only 19.6 % of adults (p = 0.017). Thirty days after their first granulocyte transfusion, 38 (59.4 %) pediatric and 61 (91 %) adult patients had died. Patients receiving the optimal dose of granulocytes had better survival outcomes, but even among this sub-group, adults were more likely to die than were children either at 30 days (OR = 8.67, 95 %CI 2.69-34.9) or 100 days (OR = 6.27, 95 %CI 1.86-25.9) after their initial granulocyte transfusion., Conclusion: Survival rates following granulocyte transfusion varied by the dose transfused and were higher in children than in adults., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose of Review: Microtransplantation (or micro-stem cell transplantation, MST) is one permutation of alloreactive immunotherapy increasingly studied in clinical trials. It is most commonly applied to patients with myeloid malignancies who are not suitable candidates for allogeneic hematopoietic cell transplantation. This review highlights the past 2 years of work on stem/progenitor cell products in the field of nonengrafting donor leukocyte infusion (NE-DLI), with a focus on applications of MST in acute myeloid leukemia (AML)., Recent Findings: Assessing the utility of MST is hampered by lack of randomized controlled trials and by variability in donor selection algorithms, treatment timing, and unknown factors. The inherent complexity of the bidirectional alloreactive reactions, implicating many cell types, makes it challenging to move beyond correlative, population-level biology toward mechanistic explanations for MST's actions in any given patient-donor pair. Yet there are indicators that by stimulating a recipient-vs.-tumor effect, MST might substantially improve complete remission rates in AML and that it might find a role in postremission therapy., Summary: The mechanistic underpinnings of MST are gradually being disentangled and its clinical development remains in early stages.

In this study, we determine the in vivo effects of injecting sub-populations of leukocytes into normal rat Achilles tendons via a controlled laboratory study. Allogenic monocytes, granulocytes, or plasma were injected into 24 healthy rat Achilles tendons. Treated and contralateral un-treated control tendons then assessed for cellularity, histologic morphology, and vascularity after 7 and 14 days. Significant increases of 221% and 249% in cellularity (P = 0.014) were seen on day 14 within Achilles tendons injected with granulocytes as compared to plasma and monocytes, respectively. Also, significant improvement in morphology (P = 0.029) between days 7 and 14 was seen for the granulocyte injected Achilles tendons. Significant increases in cellularity after an injection of granulocytes, compared to monocytes and plasma, corresponds to a significant increase in inflammation within the tissue, suggesting that leukocyte-rich platelet-rich plasma (PRP) preparations are proinflammatory and potentially catabolic when injected into tendon tissue. The concentration and composition of white blood cells within PRP preparations is variable and needs to be better understood in order to optimize clinical utility of PRP injections., Competing Interests: Authors' Disclosure Statement: The authors report that this study was supported by a grant from Arthrex.

Background: Allergic transfusion reactions are drawbacks to the benefits of transfusion. Classically, allergic transfusion reactions depend on histamine release from mast cells or basophils, but other leukocyte subsets may also be important. Thus, we propose to better define the exact leukocyte subsets involved in allergic transfusion reactions., Study Design and Methods: The overall objective of the current study was to compare the activation of specific peripheral blood leukocyte subsets (monocytes, neutrophils, eosinophils, and basophils) in a cohort of 13 patients who received chronic transfusions and had a history of allergic transfusion reactions compared with a control group of patients who received chronic transfusions and had no history of allergic transfusion reactions. Leukocyte subsets were analyzed by flow cytometry at baseline and after red blood cell transfusion, and cytokine levels in platelet-free plasma collected at the same time points were measured by Luminex assay., Results: Flow cytometry and cytokine profiles before and after transfusion did not differ significantly between patients who did and did not have a history of allergic transfusion reactions (p > 0.05). However, post-transfusion samples from both groups showed a decrease in CD63 expression in basophils, monocytes, and eosinophils and a decrease in CD45 expression in all leukocyte subsets compared with pretransfusion samples. Interleukin 10 levels increased after transfusion in the group with a history of allergic transfusion reactions (p = 0.0469), and RANTES (regulated upon activation, normal T-cell expressed and secreted) was significantly decreased post-transfusion in all patients (p = 0.0122)., Conclusion: None of the leukocyte subsets from patients who had a history of allergic transfusion reactions significantly increased in activation either before or after transfusion. All leukocyte subsets from patients who did and did not have a history of allergic transfusion reactions decreased in their activation profile upon transfusion challenge., (© 2017 AABB.)

Granulocyte transfusions (GTXs) have been used to treat and prevent infections in neutropenic patients for more than 40 years, despite persistent controversy regarding their efficacy. This narrative review attempts to complement recent systematic reviews by the Cochrane Collaboration and provide both historical context and critical assessment of the most significant clinical studies published over the years. The data suggest that properly collected and promptly infused granulocytes are active against infections, both bacterial and fungal. The most important question that remains unanswered is in which patients the administration of granulocytes will be beneficial. The preponderance of evidence suggests that granulocyte transfusions may be efficacious in few select cases as a temporizing measure to control an infection that is expected (or proven) to be refractory to optimal antimicrobial treatment, and that could otherwise be controlled by marrow recovery, which is expected to happen. In this regard, they are best considered a "bridge" that grants enough time for the recipient to develop their own response to the infection. The challenges to use GTXs successfully are both clinical, in terms of timely identifying the patients who may benefit, and logistical, in terms of optimal selection of donors and collection technique., (Published by Elsevier Inc.)

Granulocyte transfusions have a long history of being used in patients with neutropenia or neutrophil dysfunction to prevent and treat invasive fungal infections. However, there are limited and conflicting data concerning its clinical effectiveness, considerable variations in current granulocyte transfusion practices, and uncertainties about its benefit as an adjunct to modern antifungal therapy. In this review, we provide an overview on granulocyte transfusions and summarize the evidence on their role in the prevention and treatment of invasive fungal infections., (© 2017 John Wiley & Sons Ltd.)

Patients with relapsed/refractory hematologic malignancies after allogeneic stem cell transplantation have a poor prognosis due to the high rate of relapse. Techniques capable of decreasing post-transplantation relapse rates are urgently sought. This study aimed to explore the feasibility and safety of allogeneic hematopoietic stem cell transplantation (HSCT) following infusion of donor cytokine-induced killer (CIK) cells. CIK cells were generated in vitro from donor peripheral blood mononuclear cells, and were phenotyped using flow cytometric analysis. CIK cells were administered to 15 high-risk relapsed/refractory hematologic malignancy patients who were not in complete remission in multiple infusions. These patients also received allogeneic HSCT. The side effects and outcomes were recorded. All patients achieved engraftment and complete remission. After CIK cell infusion, two patients developed graft-versus-host disease (GvHD), which was controlled by additional immunosuppressant drugs. At the last follow-up, nine patients had died and six patients were surviving at a median follow-up of 1513days (range, 771-1655days). In conclusion, allogeneic HSCT combined with sequential infusion of donor CIK cells is well tolerated in salvage relapsed/refractory hematologic malignancy patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose of Review: Inconsistent results regarding the clinical efficacy of granulocyte transfusions for the treatment or prophylaxis of life-threatening infections in neutropenic patients have been attributed to insufficient number of transfused neutrophils. Since the introduction of granulocyte colony-stimulating factor (G-CSF) to the granulocyte mobilization regimen in the 1990s, the number of transfused cells significantly increased, which directly translated to a significant increase in absolute neutrophil counts in the transfused patients., Recent Findings: For therapeutic granulocyte transfusions, neither of the two randomized controlled studies in the G-CSF era could demonstrate a clear clinical benefit. However, a number of small studies or case series have suggested its clinical efficacy, including one that demonstrated the clinical response against drug-resistant invasive fusariosis. For prophylactic granulocyte transfusions, there have been scarce reports in the G-CSF era. A pulmonary reaction is the most significant adverse event after granulocyte transfusions, although its reported frequency varies among studies., Summary: Despite the expectation that the increased number of transfused neutrophils enables the clear demonstration of the clinical benefit, the role of therapeutic granulocyte transfusions remains controversial. Future directions may include: identifying the patient population who would benefit most from granulocyte transfusions; minimizing the risk of adverse events by identifying the risk factors and the prevention methods; and finding a way to prove the clinical benefit of granulocyte transfusions in therapeutic and prophylactic settings.

Introduction: A new method of reduction of tumor necrosis factor alpha activity via intradermal immunization with inactivated autoleukocytes (patent UA97493 (2015) [1]) has been presented in the article. New patents from various countries have been analyzed [2-7]., Objective: Patients with psoriasis (24) with high level of tumor necrosis factor alpha in their blood (. 30pg/ml) were immunized with autoleukocytes., Method: Leukocytes were isolated by centrifuging plasma, obtained after precipitation of a patient's heparinized peripheral venous blood. Precipitate was suspended in 1.0 - 1.5ml of a patient's blood serum and 0.1ml of blood was injected into the skin of the back. For determination of autoleukocyte immunization efficacy, concentration of tumor necrosis factor alpha in a patient's blood was compared prior to immunization and at different periods after immunization., Results: In 30 days after single immunization, a considerable decrease in cytokine concentration was observed in all patients (100%); it reduced to zero in 16 out of 24 of immunized individuals (66.7%). The degree of reduction and duration of the achieved effect were individual, thus, if necessary the immunization was repeated several times. The procedure was well tolerated, and general condition of patients was improved., Conclusion: The method of reduction of tumor necrosis factor alpha activity is recommended for implementation into clinical practice.

Background: Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in people with prolonged disease-related or therapy-related neutropenia. Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in people who lack their own functional granulocytes. This is an update of a Cochrane review first published in 2009., Objectives: To determine the effectiveness and safety of prophylactic granulocyte transfusions compared with a control population not receiving this intervention for preventing all-cause mortality, mortality due to infection, and evidence of infection due to infection or due to any other cause in people with neutropenia or disorders of neutrophil function., Search Methods: We searched for randomised controlled trials (RCTs) and quasi-RCTs in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), CINAHL (from 1937), theTransfusion Evidence Library (from 1980) and ongoing trial databases to April 20 2015., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing people receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events., Data Collection and Analysis: We used standard methodological procedures expected by The Cochrane Collaboration., Main Results: Twelve trials met the inclusion criteria. One trial is still ongoing, leaving a total of 11 trials eligible involving 653 participants. These trials were conducted between 1978 and 2006 and enrolled participants from fairly comparable patient populations. None of the studies included people with neutrophil dysfunction. Ten studies included only adults, and two studies included children and adults. Ten of these studies contained separate data for each arm and were able to be critically appraised. One study re-randomised people and therefore quantitative analysis was unable to be performed.Overall, the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcome estimates being imprecise.All-cause mortality was reported for nine studies (609 participants). There was no difference in all-cause mortality over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (seven studies; 437 participants; RR 0.92, 95% CI 0.63 to 1.36, very low-quality evidence).Mortality due to infection was reported for seven studies (398 participants). There was no difference in mortality due to infection over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (six studies; 286 participants; RR 0.69, 95% CI 0.33 to 1.44, very low-quality evidence).The number of people with localised or systemic bacterial or fungal infections was reported for nine studies (609 participants). There were differences between the granulocyte dose subgroups (test for subgroup differences P = 0.01). There was no difference in the number of people with infections over 30 days between people receiving prophylactic granulocyte transfusions and those that did not in the low-dose granulocyte group (< 1.0 x 10(10) granulocytes per day) (four studies, 204 participants; RR 0.84, 95% CI 0.58 to 1.20; very low-quality evidence). There was a decreased number of people with infections over 30 days in the people receiving prophylactic granulocyte transfusions in the intermediate-dose granulocyte group (1.0 x 10(10) to 4.0 x 10(10) granulocytes per day) (4 studies; 293 participants; RR 0.40, 95% CI 0.26 to 0.63, low-quality evidence).There was a decreased number of participants with bacteraemia and fungaemia in the participants receiving prophylactic granulocyte transfusions (nine studies; 609 participants; RR 0.45, 95% CI 0.30 to 0.65, low-quality evidence).There was no difference in the number of participants with localised bacterial or fungal infection in the participants receiving prophylactic granulocyte transfusions (six studies; 296 participants; RR 0.75, 95% CI 0.50 to 1.14; very low-quality evidence).Serious adverse events were only reported for participants receiving granulocyte transfusions and donors of granulocyte transfusions., Authors' Conclusions: In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is low-grade evidence that prophylactic granulocyte transfusions decrease the risk of bacteraemia or fungaemia. There is low-grade evidence that the effect of prophylactic granulocyte transfusions may be dose-dependent, a dose of at least 10 x 10(10) per day being more effective at decreasing the risk of infection. There is insufficient evidence to determine any difference in mortality rates due to infection, all-cause mortality, or serious adverse events.

Hydroxyethyl starch (hetastarch) is a synthetic glucose compound with extensive clinical use as a volume expander. Because of its red blood cell-sedimenting properties, hetastarch plays a major role in preparation of granulocyte products. Recent concerns have been raised about the use of hetastarch in critically ill patients for the development of renal injury and other severe adverse events. In contrast, granulocyte donors receive much less of this compound during collection procedures, and over many years, minimal toxicity has been documented in these individuals. Furthermore, granulocyte products contain very little hetastarch, and ill effects on renal function have not been associated with their administration. This review assesses available information about the toxicity profile of hetastarch in critically ill patients requiring a volume expander as well as granulocyte donors and recipients. Because of the lack of toxicity in these latter two groups, hetastarch should be available for preparation of granulocyte products and their administration., (© 2014 AABB.)

One of the most important morbidity causes of aplastic anemia is invasive fungal infections. It could not be possible to take control of infection without neutrophils despite the recent developments in the antifungals. In this presented case, a patient with severe aplastic anemia, granulocyte transfusion were administered as 46 times because of the presence of widely invasive aspergillosis and resistance. Only fever reaction was observed as a complication of transfusion amongst the other complications such as acute lung damage, alloimmunisation, and graft-versus-host disease. Granulosit transfusions should not be avoided in patients who had an indication for., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective/aim: To evaluate the safety of transfusing pooled, whole blood-derived granulocytes in additive solution and plasma (GASP) in 30 recipients., Background: Demand for granulocytes in England has increased five-fold. With the advantages of reduced red cell, plasma and overall volume, GASP maintains function in vitro., Methods and Materials: Observations were recorded prior to and post transfusion. Increments were recorded at 1 h and the following morning. Leucocyte antibody screening was undertaken prior to and at 1-6 months following transfusion., Results: Thirty patients aged between 8 months and 68 years received 221 GASP in 148 transfusion episodes. GASP contained an average of 1.0 × 10(10) granulocytes in 207 mL. Adults usually received two packs and children 10-20 mL kg(-1). Children and adults received a median [interquartile range (IQR)] dose of 12.5 (9.1-25.3) and 19.7 (12.0-25.8) × 10(9) granulocytes per transfusion, respectively. There was one episode of transfusion-associated circulatory overload (TACO) in a patient with chronic cardiac failure following 600 mL of unpooled granulocytes, other fluids and one GASP. New leucocyte alloimmunisation occurred in 3/30 recipients 10%. No other significant reactions were reported. Median peripheral blood neutrophil increments at 1 h post transfusion were 0.06 (IQR, 0.01-0.17) in children and (0.03) (IQR, 0-0.16) in adults., Conclusion: GASP has a similar safety profile to other sources of granulocytes for patients with refractory infection or in need of secondary prophylactic transfusion. Further studies are required to clarify the role of GASP in the treatment of neutropenic patients., (© 2012 The Authors. Transfusion Medicine © 2012 British Blood Transfusion Society.)

It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 10³ID₅₀ as measured by intracerebral inoculation of tg338 mice (ID₅₀ IC in tg338). This was consistent with a whole blood titer greater than 10³·⁶ID₅₀ IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation.

Neutrophils play an essential role in the defense of the body against bacterial and fungal infections. Disorders of their number or function significantly increase the risk of life-threatening infection. In spite of the development of growth factors, new broad spectrum antibiotics and antifungal drugs against nearly all known pathogens, severe neutropenia associated with bacterial or invasive fungal infections remains a major cause of morbidity and mortality in patients undergoing aggressive cancer chemotherapy or hematopoietic stem cell transplantation. Lately, an interest about granulocyte transfusions was renewed, what is a logical approach in the management of patients with prolonged 'reversible' severe neutropenia and severe infection, which is not controlled with appropriate antimicrobial and supportive treatment, including recombinant hematopoietic growth factors. It was a consequence of advances in the field of apheresis science, use of sedimenting agents and especially advances in mobilization of granulocytes to the peripheral blood. It became now possible to collect large numbers of neutrophils. Therefore, the clinical use of granulocyte transfusions, as a potential life saving treatment option in patients with severe neutropenia and uncontrolled infection in spite of appropriate antimicrobial therapy should be considered, with regard to possible benefits and risks (Ref. 74).

Granulocyte transfusions may be useful for neutropenic pediatric patients with refractory bacterial or fungal infections. Many potential adverse sequelae associated with granulocyte transfusions are well recognized, including febrile reactions, fluid overload, alloimmunization, and lung injury. Other potential adverse sequelae, however, are less well known. This case report describes an infant with familial hemophagocytic lymphohistiocytosis who developed polycythemia (hemoglobin 10-17.6 g/dl) following four daily transfusions of 20 ml/kg of apheresis collected, steroid stimulated donor granulocytes. Expanded knowledge of potential risks of transfused granulocytes will allow for rapid recognition of transfusion-related complications, should they occur., (Copyright © 2011 Wiley Periodicals, Inc.)

Background Aims: This single-center 10-year retrospective study assessed clinical efficacies and adverse events and determined prognostic factors in patients with hematologic disease and febrile neutropenia treated with granulocyte transfusions (GT) from unrelated healthy donors stimulated with recombinant human granulocyte-colony-stimulating factor (rhG-CSF) and dexamethasone., Methods: Between September 1999 and June 2009, 1027 therapeutic GT were performed for the treatment of 170 episodes of febrile neutropenia in 157 patients. Efficacy analysis included 979 GT for 138 episodes in 128 patients who received at least three GT per episode. Adverse event analysis included all patients who received at least one GT., Results: The median granulocyte dose was 0.96 × 10(9)/kg/transfusion (range 0.47-1.80 × 10(9)/kg/transfusion). Infection was controlled in 73 episodes (52.9%). The 28-day infection-related survival rate was 64.7 ± 4.1%. The dose of granulocytes transfused did not correlate with clinical outcome. Multivariate analysis revealed that septic shock and pneumonia/multiple primary infection sites were related to infection control failure. Furthermore, refractory underlying disease and septic shock were associated with shorter infection-related survival. Massive hemoptysis (3.5%) and respiratory failure (5.9%) occurred in a few patients. Prior pneumonic infiltration, azotemia and a larger volume of daily GT were associated with serious respiratory complications., Conclusions: GT therapy is a viable adjunctive treatment option for febrile neutropenia as a bridge to autologous hematopoietic recovery in patients with hematologic disease with tolerable toxicity. GT therapy requires close monitoring in patients with prior pneumonic infiltration and azotemia. It is recommended that transfusion with higher volumes is avoided.

Objective: To investigate whether the higher prevalence of postoperative complications in cardiac surgery after transfusion of leukocyte-containing red blood cells can be related to inflammatory mediators., Design: Analysis of inflammatory markers interleukin-6, interleukin-10, interleukin-12, and procalcitonin in patients participating in a randomized trial comparing leukocyte-depleted with leukocyte-containing, buffy-coat-depleted red blood cells., Setting: Two university-affiliated hospitals in the Netherlands., Subjects: A total of 346 patients undergoing cardiac valve surgery with a complete series of pre- and postoperative blood samples., Measurements and Main Results: There were no differences in the cytokines and procalcitonin concentrations between both study arms when the patients arrived in the intensive care unit. In subgroups, patients who received zero to three red blood cell transfusions showed similar cytokine concentrations in both study arms, whereas patients with > or = 4 red blood cell transfusions had significantly higher interleukin-6 concentrations in the leukocyte-containing, buffy-coat-depleted red blood cell group. Patients who developed postoperative infections and multiple organ dysfunction syndrome showed, respectively, increased concentrations of interleukin-6 and interleukin-12 in the leukocyte-containing, buffy-coat-depleted, red blood cell group. The interaction tests in these subgroups showed significantly different reaction patterns in the leukocyte-containing, buffy-coat-depleted red blood cell group compared with leukocyte-depleted red blood cell group for interleukin-6 and interleukin-12. Multivariate analysis showed a high interleukin-6 concentration with multiple organ dysfunction syndrome and both high interleukin-6 and interleukin-10 concentrations with hospital mortality., Conclusions: Allogeneic leukocyte-containing blood transfusions compared with leukocyte-depleted blood transfusions induce dose-dependent significantly higher concentrations of proinflammatory mediators in the immediate postoperative period after cardiac surgery. High concentrations of interleukin-6 are strong predictors for development of multiple organ dysfunction syndrome, whereas both interleukin-6 and interleukin-10 are associated with hospital mortality. These findings suggest that leukocyte-containing red blood cells interfere with the balance between postoperative proinflammatory response, which may further affect the development of complications after cardiac surgery.

Background and Objectives: CIK cells are a novel population of efficient immune effector cells with high antitumour activity mainly due to the high proliferation of CD3(+)CD56(+) cells, so may play a role in the development of new forms of adoptive cellular immunotherapy. We started a pilot clinical trial with autologous CIK cells in patients with refractory lymphoma and metastatic solid tumours. This study was aimed at determining the feasibility of generating a sufficient number of CIK cells in heavily pretreated patients and at assessing treatment toxicity., Design and Methods: CIK cells were generated from peripheral blood mononuclear cells (MNC) and incubated in the presence of IFN-gamma followed by OKT3 and IL-2. Treatment schedule consisted of three cycles of CIK cells infusions at an interval of 3 weeks., Results: At present 12 patients were enrolled: 6 advanced lymphomas, 5 metastatic kidney carcinoma and 1 hepatocellular carcinoma (HCC). The median number of transferred cells per patient was 28 x 10(9) (range, 6-61). Protocol adherence was excellent and the toxicity profile was favourable. After CIK cells infusion, the absolute median count of lymphocytes, CD3(+), CD8(+) and CD3(+)CD56(+) cells significantly increased in patient's peripheral blood. Clinical outcome appeared promising: three patients had complete response (CR) and two patients had stabilization of disease with a median follow-up of 33 months (range, 9-44)., Interpretations and Conclusions: These preliminary data showed that adoptive immunotherapy with CIK cells is a safe therapy with some suggestion of efficacy that significantly enhances immune functions increasing absolute numbers of effector cells without side effects. If confirmed in larger scale studies, these promising results may have a favourable impact on conventional treatment strategy of malignancies.

Background: Granulocyte transfusions (GTs) may increase the absolute neutrophil count (ANC) before hematopoietic regeneration in neutropenic patients after chemotherapy or hematopoietic stem cell transplantation and support anti-infective immunity., Procedure: We assessed efficacy and tolerability of 778 GTs in 70 treatment episodes of 49 children and 10 young adults [median age 6.28 y (range: 0.13 to 17.7 y) and 21 y (18.0 to 28.0), respectively] suffering from bacterial (n=55) and/or fungal (n=31) infections during neutropenia owing to conventional chemotherapy (n=14), hematopoietic stem cell transplantation conditioning (n=44), or the underlying disease (n=1). We analyzed the impact of body weight, organ dysfunction, neutrophil dose on ANC increment, infection elimination, and survival., Results: The median day-5 ANC increment was 1460/microL, correlating to the administered dose. However, 28-day survival did not correlate to the neutrophil dose nor to the ANC increment, potentially owing to the high number of neutrophils transfused to all patients (median >6x10(9)/kg within 5 d). The 28-day survival probability of the total patient cohort was 0.72+/-0.06 and the 100-day survival was 0.52+/-0.07. Adverse reactions were rare including fever (< or =World Health Organization grade III, 14%), chills (3%), and mild pulmonary complications (1%)., Conclusions: These data corroborate the empirical evidence that GT with sufficient cell doses and rapid availability are a feasible, well-tolerated supplemental means to fight severe infections in neutropenic patients.

Donor leukocyte infusion (DLI) is used after both myeloablative and non-myeloablative stem-cell transplantation to treat and prevent relapse, to establish full donor chimerism, and to treat and prevent infections. The major treatment-related complication of DLI is graft-versus-host disease (GVHD). The presentation and treatment of GVHD after DLI is similar to its presentation and treatment after stem-cell transplantation, with some notable exceptions. While GVHD and graft-versus-tumor (GVT) effects are highly correlated after DLI, some patients experience remission without GVHD. Studies to define tumor-specific target antigens and GVT effector cells, as well as strategies of donor T-cell manipulation and optimization of DLI dose and schedule, may ultimately lead to the consistent ability to separate GVHD from GVT activity, improvement in the safety and specificity of DLI, and enhancement of the anti-tumor activity of donor T cells.

Introduction: The role of granulocyte transfusions (GT) in patients with neutropenia-related infections remains controversial., Materials and Methods: A retrospective analysis of 47 neutropenic patients, treated with 348 consecutive GTs for life-threatening infections between 1999 and 2004, is presented., Results: The only grade III-IV toxicity observed in GT recipients was respiratory deterioration (n = 6, 12.8%). The overall infection-related mortality (IRM) approached 38%. Achievement of a neutrophil count of > 700 cells per microl after at least 50% of days of GTs (n = 33, 70%) significantly correlated with reduced IRM (27.3% vs. 64.3%, P < 0.02). GT doses of > 2 x 10(10) neutrophils per bag appeared to increase both neutophil and platelet counts following transfusion., Conclusion: GTs are safe and should be considered for patients with life-threatening neutropenic infections. However, prospective randomized studies of GTs are the only way to establish the true role of GTs.

Blood transfusion is a newly recognized cause of microchimerism, the stable persistence of a minor population of allogeneic cells. Relatively recent advances in polymerase chain reaction technology have spawned new information about the frequency and aetiology of transfusion-associated microchimerism (TA-MC). Although conceptually related to fetal-maternal microchimerism, TA-MC is a distinct and separate entity. Evidence of TA-MC has been strongest among patients with severe traumatic injuries who receive relatively fresh blood products shortly after an episode of massive haemorrhage. The presence of a focal deficit in the cellular immunologic repertoire prior to transfusion that happens to match a blood donor's human leucocyte antigen type also appears to be an important predisposing factor. TA-MC seems to be common (affecting approximately 10% of transfused injured patients), enduring (lasting years to decades) and pronounced (involving up to 5% of circulating leucocytes and multiple immunophenotypic lineages suggestive of haematopoietic engraftment). Further study of this topic may reveal important information regarding potential clinical consequences of TA-MC, as well as basic haematologic and immunologic processes.

Intention-to-treat analyses of randomized controlled trials (RCTs) of the association between non-white-blood-cell (WBC)-reduced allogeneic blood transfusion (ABT) and postoperative infection were reported as the reason why meta-analyses of RCTs of this association have produced discordant results. We examined three possible reasons for disagreements between meta-analyses: (i) sources of medical heterogeneity and integration of RCTs despite extreme heterogeneity; (ii) reliance on as-treated (vs. intention-to-treat) comparisons; and (iii) inclusion (or not) of the three most recent RCTs. When nine RCTs reported up to 2002 were combined despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found an association between non-WBC-reduced ABT and postoperative infection [summary odds ratio (OR) = 1.38, 95% confidence interval (CI) 1.03-1.85, P < 0.05; and summary OR = 1.56, 95% CI 1.06-2.31, P < 0.05, respectively]. When 12 RCTs reported up to 2005 were integrated despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found no association of non-WBC-reduced ABT with postoperative infection (summary OR = 1.24, 95% CI 0.98-1.56, P > 0.05; and summary OR = 1.31, 95% CI 0.98-1.75, P > 0.05, respectively). In both analyses, the separate integration of four RCTs transfusing red blood cells (RBCs) or whole blood filtered after storage showed an association between non-WBC-reduced ABT and postoperative infection, whereas the separate integration of six (or nine) RCTs, reported through 2002 or 2005, and transfusing prestorage-filtered RBCs showed no association, whether intention-to-treat or as-treated comparisons were used. Thus, the published meta-analyses have produced discordant results because they did (or did not) investigate medical sources of heterogeneity and did (or did not) include the most recent RCTs. Intention-to-treat and as-treated comparisons produced concordant results.

Background and Aim: The role of leucocyte antibodies in donors is poorly understood in pathogenesis of transfusion-related acute lung injury (TRALI). We examined antibodies in donors and traced recipients transfused with their blood components., Material and Methods: Antibodies were examined in 1043 donors by five methods, look back performed in 26 recipients., Results: Anti-human leucocyte antigen detected by enzyme-linked immunosorbent assay in 9.8% women but none in men. Specificities identified using FlowPRA, antibodies detected after several months. TRALI reported in one recipient from immunized donor. In 11 of 26 recipients without TRALI, cognate antigens were identified., Conclusion: Detection of antibodies in donors cannot predict TRALI, even in recipients with cognate antigen(s).

Infection associated with therapy-related neutropenia continues to be a major cause of morbidity and mortality. Renewed interest in granulocyte transfusion therapy as treatment for this condition has been generated by the observation that large doses of granulocytes can be obtained from donors who have been stimulated with granulocyte colony-stimulating factor (G-CSF). Granulocytes collected from these donors have been shown to effectively raise the patient's neutrophil count and appear to function normally as judged both by in vitro and in vivo measures. The evidence for clinical efficacy is limited to that of case reports and small series, and the results are not uniform. Randomized controlled clinical trials are needed to determine whether this therapy is useful in either clearing infections or prolonging survival.

Background: Bacterial and fungal infections in profound neutropenia after chemotherapy are associated with high mortality despite appropriate antibacterial and antifungal treatment. Granulocyte transfusions are used as a therapeutic addendum, but concern regarding pulmonary reactions often results in delayed use in clinical practice. Accordingly, many patients are already at advanced stages of their infectious disease once granulocytes are transfused. Thus, a prospective Phase II trial was conducted to test the safety and efficacy of therapeutic early-onset granulocyte transfusions in immunocompromised children with neutropenia and severe infections., Study Design and Methods: Twenty-seven children with hematologic disorder or malignancy and severe neutropenia with clinically and/or microbiologically documented severe infection unresponsive to standard treatment were included. They received granulocyte colony-stimulating factor (G-CSF)-elicited, crossmatched granulocyte concentrates every other day until complete recovery from infection was documented., Results: A median of two granulocyte transfusions with a median of 8 x 10(8) granulocytes per kilogram of body weight were administered. All transfusions were well tolerated, and no pulmonary symptoms were observed. A total of 92.6 percent of our patients were able to clear their initial infection, and 81.5 percent were alive and without signs or symptoms of their infection 1 month later. All six children with aspergillosis cleared their infection., Conclusions: G-CSF-elicited, crossmatched granulocyte concentrates are a safe and efficient therapeutic addendum in immunocompromised children with prolonged neutropenia and severe infections. Early transfusion of granulocyte concentrates can lead to an overall response rate of 92.6 percent without adverse events. Randomized clinical trials with an early-onset design are required to determine appropriate clinical applications.

Introduction: In this retrospective, uncontrolled, observational study, the effect of granulocyte colony-stimulating factor (G-CSF)-stimulated granulocyte transfusions (GTX) in neutropenic paediatric patients with sepsis was evaluated., Patients and Methods: Granulocytes were collected from unrelated, ABO group-matched and cytomegalic-antibody compatible donors. For neutrophil mobilization, donors received a single subcutaneous dose of glycosylated G-CSF (Lenograstim, Chugai Pharma, Japan) plus oral dexamethasone (8 mg). In total, 168 (range 1-19 per patient) GTX were transfused in 32 children with a median age of 7.4 (0.25 to 16) years., Results: The underlying diseases comprised predominantly haematooncological malignancies (31 children). In 15 of 32 patients, neutropenia was related to allogeneic stem cell transplantation. All children suffered from sepsis based on international criteria (fever, tachycardia, respiratory rate >2 SD above normal in the context of a suspected or proven infection). In ten children bacteria were isolated, in six children a fungal infection was diagnosed and four sepsis episodes were caused by viral infections. GTX contained a median neutrophil number of 6.3 (range 1.9-13.9)x10(10) per transfusion and obtained a sustained haematological response after GTX. Nineteen out of 32 children survived the neutropenic sepsis, particularly nine out of 11 patients with bacterial sepsis., Discussion: In contrast to the non-survivors, we observed a significant decrease in the C-reactive protein levels shortly after initiation of the GTX treatment in the surviving patients. A clear-cut benefit of GTX for children with neutropenic sepsis cannot be concluded from these data, but in children with (severe) bacterial sepsis refractory to antibiotic treatment, GTX were feasible, safe and could reduce mortality rates in this subgroup of patients.

Purpose of Review: Donor leukocyte infusions provide direct and potent graft-versus-tumor activity to treat relapse after allogeneic stem cell transplantation. Extensive data are available on the use of donor leukocyte infusion after matched-sibling stem cell transplantation, but reports are remarkably few on the use of donor leukocyte infusion after unrelated-donor stem cell transplantation. But the role for unrelated-donor leukocyte infusion is not well established., Recent Findings: The dramatic success of donor leukocyte infusion to treat relapse after matched-sibling stem cell transplantation has led to the use of unrelated-donor leukocyte infusion in many patients. Several case studies suggest that unrelated-donor leukocyte infusion effectively induces direct graft-versus-tumor reactions with toxicity comparable to that of matched-sibling donor leukocyte infusion. Important issues include the relationship between dose and response/toxicity appropriate timing, dose, and schedule; and identification of the best tumor targets. In particular nonmyeloablative transplant strategies using unrelated donors are expanding rapidly, but relapse rates are high. There is a paucity of data on unrelated-donor leukocyte infusion in this setting., Summary: This review summarizes recent data on the use of unrelated-donor leukocyte infusion. We discuss anticipated outcomes and identify areas under active investigation in both ablative and nonmyeloablative unrelated-donor stem cell transplantation.

Although dramatically effective for relapsed chronic myelogenous leukemia (CML), successful donor leukocyte infusion (DLI) remains limited primarily by inadequate responses for patients with diseases other than CML and by toxicity related to graft-versus-host disease (GVHD). Acute GVHD grades 2 to 4 follows 34% to 47% of infusions and chronic GVHD occurs in 33% to 61% of cases. Strategies to reduce the incidence and severity of GVHD while preserving the graft-versus-leukemia (GVL) effect, such as low-dose DLI, depletion of GVHD effector cells, and tumor-specific DLI, are reviewed.

Purpose of Review: Granulocyte transfusions have been used for more than four decades. Several issues have complicated the analysis of previous studies, including the utilization of improved antimicrobials, the effects of recipient alloimmunization and variable cell dose. The use of granulocyte colony-stimulating factor for donor stimulation has revived interest in granulocyte transfusion. The aim of this review is to evaluate the most recent studies in granulocyte transfusion therapy and their clinical applicability., Recent Findings: Granulocyte colony-stimulating factor use has increased the granulocyte yield by approximately fourfold. Multiple recent studies have shown that granulocyte transfusions can be helpful in controlling severe infections progressing despite the use of appropriate antibiotics, with a response rate of 40-80% with variability in results depending on patient characteristics. This benefit is limited to a small patient population as the incidence of prolonged reversible neutropenia is relatively small. Severe side effects have been rare in those studies., Summary: Granulocyte transfusions are beneficial in neutropenic patients with severe uncontrolled infection. The underlying disease process is the major determinant of outcome in these patients. Because granulocyte transfusions are not commonly used, centers are not currently able to provide transfusions in a timely fashion. Nonalloimmunized patients can receive cells from nonmatched ABO compatible donors, while alloimmunized patients should receive granulocytes from either HLA-matched donors or donors selected by leukoagglutination or lymphocytotoxicity crossmatching. Further studies are needed to clarify the optimal starting time and frequency of transfusions, and the best method for identifying donor-recipient compatibility.

Background and Objectives: Host-virus interactions play a central role in determining the prognosis of hepatitis B virus infection. Multi-factors activated immune cells (MAICs) are autologous peripheral blood mononuclear cells activated with anti-CD3 monoclonal antibody, interleukin-2 and interferon-gamma. The present pilot clinical trial was designed to determine whether adoptively transferred MAICs inhibit the replication of hepatitis B virus and is safe for patients., Study Design: Fourteen patients with chronic hepatitis B were enrolled in the study. A total of (1.5-4.0)x10(9) peripheral blood mononuclear cells were isolated from each patient and activated by anti-CD3 monoclonal antibody, interleukin-2 and interferon-gamma in vitro for 10 days to produce MAICs. Cell phenotypes and levels of cytokine secretion were determined during cell culture. Patients were followed up for 1 year after the transfusion of MAICs., Results: After 10 days of culture, peripheral blood mononuclear cells were expanded to a mean fold of 4.68+/-1.78 and activated effectively, as demonstrated by CD25 expression and cytokine secretion. Cell activation peaked on day 4. All patients accepted the MAICs transfusion with some slight adverse events, and fulminant hepatitis and bilirubinemia were not observed. Significant HBV inhibition was observed in 8 out of 14 patients, in which 5 patients achieved complete response (defined as that serum HBV DNA levels below the detection limit, occurrence of HBeAg seroconversion and normalization of ALT were observed together after MAICs transfusion and kept for at least 6 months) and 3 patients achieved partial response (defined as that serum HBV DNA levels below the detection limit, occurrence of HBeAg disappearance and normalization of ALT were observed together in 6 months after MAICs transfusion, but kept for less than 6 months)., Conclusion: These findings strongly suggest that MAICs transfusion, which effectively inhibits the replication of hepatitis B virus, is safe for patients.

Background: Donor stimulation with granulocyte-colony-stimulating factor (G-CSF) has increased the number of neutrophils (PMNs) that can be collected for granulocyte transfusion therapy. Clinical utility, however, has been limited by the inability to store functional PMNs ex vivo. This study was conducted to determine whether granulocyte products from G-CSF-stimulated donors could be effectively stored at reduced temperature (22 degrees C vs. 10 degrees C) with maintenance of functional properties in vitro and in vivo., Study Design and Methods: Nine normal subjects received G-CSF (600 microg subcutaneously) 12 hours before centrifugation leukapheresis. Granulocyte products were divided and stored for 24 and 48 hours under four conditions: 1) 22 degrees C; 2) 22 degrees C, with supplemental G-CSF (100 ng/mL); 3) 10 degrees C; and 4) 10 degrees C, with supplemental G-CSF. Functional PMN activity during ex vivo storage was assessed in vitro and in vivo by the skin-window technique for granulocytes stored at 10 degrees C for 24 hours., Results: Surface expression of CD11b/CD18, CD14, CD16, CD32, and CD64 was maintained during 48-hour storage at reduced temperature. Inducible respiratory burst activity, bactericidal activity, and fungicidal activity were preserved during storage for 48-hour storage at 10 degrees C. Proinflammatory cytokine production was decreased in product stored at 10 degrees C. Supplemental G-CSF ex vivo did not substantially improve functional activity during storage. After storage at 10 degrees C for 24 hours, in vitro chemotactic potential was maintained, and transfused granulocytes retained capacity to circulate and migrate appropriately in vivo., Conclusions: Granulocyte product collected by centrifugation leukapheresis from G-CSF-stimulated donors can be effectively stored at subphysiologic temperature for 24 hours with preservation of functional activity. Storage at 10 degrees C appears to be slightly superior to storage at 22 degrees C.

Donor leukocyte infusion (DLI) has been successfully used for some life-threatening viral infections after stem cell transplantation (SCT). We describe here the first case of DLI treatment for cytomegalovirus (CMV) retinitis. A 49-year-old female patient with AML, M1 underwent SCT with a reduced-intensity conditioning regimen from HLA-haploidentical son. On day +140, the patient developed CMV retinitis of her left eye despite the continuing antiviral therapy. DLI at a dose of 1 x 10(5) CD3+ cells/kg was added to ganciclovir and foscarnet therapy. Eighteen days after the DLI, the funduscopic findings revealed improvement of the retinitis and the development of vitreous inflammation. Simultaneously, the number of CD4+ cells in the peripheral blood rapidly increased. Thus, we consider it likely that DLI induced a local immune response against CMV antigens, which resulted in the immune recovery vitritis. This case suggested the potentiality of DLI for the treatment of CMV retinitis.

Background: The efficacy and feasibility of donor granulocyte transfusion therapy (GTX) have changed considerably over the past four decades. The authors sought to determine the impact of high-dose (approximately 5.5 x 10(10) cells) GTX in patients with candidemia., Methods: The authors' case-control retrospective analysis comprised 491 consecutive patients treated at The University of Texas M. D. Anderson Cancer Center (Houston,TX) from 1993 to 2000. The cohort included 29 patients with Candida species bloodstream infection who had received GTX and 462 who had not., Results: Both groups were comparable in age, gender, APACHE II score, recent chemotherapy received, broad-spectrum antibiotics, systemic corticosteroids, radiotherapy, intravascular catheter, and concordant antifungal therapy (P > or = 0.1). The patients who received GTX compared with those who did not had a higher incidence of underlying leukemia (86% vs. 29%, P <0.001), persistent neutropenia (59% vs. 18%, P <0.001), non-Candida albicans candidemia (Candida glabrata, 35%; Candida krusei, 31%: 90% vs. 67%, P=0.01), and breakthrough invasive mycosis (62% vs. 23%, P <0.001). Neutropenia was more prolonged in patients who received GTX (28 vs. 10 days, P <0.001). Also, more of the patients who received GTX had received hematopoietic stem cell transplantations (28% vs. 13%, P = 0.03), exposure (within 4 weeks) to antifungals (79% vs. 38%, P <0.001), and stays in critical care units (62% vs. 40%, P=0.02). The overall attributable mortality rate for 25 evaluable recipients of GTX was 48% (n=12), compared with 45% (n=115) of 254 evaluable patients in the control group (P=0.5). Of the 158 patients with leukemia, 25 (16%) had received GTX. In patients with leukemia, more of those who had received GTX experienced disseminated candidiasis (44% vs. 26%; P <0.07) and persistent neutropenia (68% vs. 43%, P <0.02), had candidemia that was more prolonged (> 72 hours, P <0.02), and had more stays in critical care units (68% vs. 44%, P <0.03). On the bases of a reduced multivariate model, a significantly increased risk of death was found for patients with hematopoietic stem cell transplantation (odds ratio [OR]=2.51; 95% confidence interval [95% CI], 0.99-6.31; P <0.05), for patients with persistent neutropenia (OR=4.57; 95% CI, 1.99-10.47; P <0.0003), and for patients with leukemia who also had prolonged candidemia (OR=3.59; 95% CI, 1.61-7.98; P <0.002), disseminated candidiasis (OR=5.19; 95% CI, 2.17-12.42; P <0.0002), or non-C. albicans candidemia (OR=5.02; 95% CI, 1.07-23.64; P <0.04). In patients with leukemia, death was attributable to candidemia in 50% of the GTX recipients, compared with 59% of the non-GTX patients who had received antifungal therapy alone (P=0.4)., Conclusions: Despite the presence of multiple predictors of increased mortality, high-dose GTX therapy in these high-risk patients with cancer was associated with better than expected survival rates.

The efficacy of granulocytes transfusions (GTX) in either the prevention or treatment of neutropenic sepsis has been a controversial issue. Early studies employing steroid mobilised GTX showed variable, dose-dependent results and significant pulmonary toxicity was reported. With the introduction of the recombinant myeloid growth factor, granulocyte-colony stimulating factor (G-CSF), the quantity of granulocytes that could be harvested was substantially increased leading to renewed interest in the clinical application of GTX. The administration of G-CSF to normal donors leads to significantly higher pre-harvest neutrophil counts and consequently larger granulocyte harvests. Infusion of G-CSF stimulated GTX results in measurable increases in the recipients' neutrophil count and may reduce the duration and severity of neutropenia. However, the efficacy of these GTX in treating or preventing established neutropenic sepsis remains to be established in prospective controlled clinical trials.

Background and Objectives: An association of white blood cell (WBC) reduction with decreased mortality was reported by one observational, before-and-after study. A meta-analysis was undertaken to examine whether this finding is supported by all the evidence currently available from before-and-after studies, and whether these studies support an association of WBC reduction with a decreased risk of postoperative infection., Materials and Methods: Observational, before-and-after studies were retrieved that reported on postoperative infection and/or mortality between January 1997 and June 2003. Six studies met the criteria for meta-analysis. Unadjusted summary odds ratios (ORs) of postoperative infection or mortality in patients transfused after (compared with before) WBC reduction were calculated across the studies if the hypothesis of homogeneity was not rejected. Adjusted summary ORs were calculated across three studies that had reported multivariate analyses., Results: There was an unadjusted association of WBC reduction with a decreased risk of postoperative infection [summary OR = 0.93; 95% confidence interval (95% CI), 0.88-0.99; P < 0.01] that did not persist following adjustment for confounding factors (summary OR = 0.94; 95% CI, 0.85-1.04; P > 0.05). There was neither an unadjusted nor an adjusted association of WBC reduction with decreased mortality (summary OR = 0.94; 95% CI, 0.71-1.23; P > 0.05; and OR = 0.92; 95% CI, 0.80-1.05; P > 0.05, respectively)., Conclusions: An association of WBC reduction with decreased mortality was not detected across the results available from all before-and-after studies. An unadjusted association of WBC reduction with a decreased risk of postoperative infection exists, but this was not detected across the three studies that reported multivariate analyses.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood component transfusion therapy. Currently, cellular blood components for patients recognized at risk for TA-GVHD are irradiated prior to transfusion in order to prevent this complication. Considerable progress has been made in elucidating the pathophysiology of this highly morbid complication, but questions as to which patients are at risk and what is the most robust technology to prevent TA-GVHD remain. As new technologies for inactivating or modulating leukocyte function are introduced, the question of how to evaluate these technologies becomes relevant. Over the past two decades, a number of research groups have explored technology to inactivate infectious pathogens and leukocytes contaminating cellular blood components. Few clinicians have an in-depth understanding of the methods or the criteria for selection of how to approach new technologies for leukocyte inactivation with potential to replace current methods. This mini review focuses on the salient aspects of current and evolving technology for prevention of TA-GVHD.

Objective: To review the current status of risks of blood transfusion., Data Sources, Extractions, and Synthesis: English-speaking literature, literature search using key works, human data, and follow-up with key bibliographic citations., Conclusions: Substantial advances have been achieved in blood safety during the last 20 yrs, particularly for transfusion-transmitted viral infections. Currently, the most serious known risks from blood transfusion are administrative error (leading to ABO-incompatible blood transfusion), transfusion-related acute lung injury, and bacterial contamination in platelet products. Emerging pathogens, such as West Nile virus infection emphasize the need for implementation of proactive strategies, such as pathogen inactivation technologies, as well as reactive strategies, such as nucleic acid testing, to ensure continued advances in blood safety.

Data of 507 granulocyte donations from 183 donors were evaluated. No severe granulocyte colony-stimulating factor (G-CSF)-related side-effects were observed. Three donors complained of severe itching following infusion of hydroxyethyl starch (HES). A high proportion (85%) of the donors stated that they would donate granulocytes again. The mean granulocyte yield was 4.3 x 10(10). High-molecular-weight HES resulted in a significantly higher yield compared with low-molecular-weight HES. Mild, but no severe, adverse transfusion reactions were observed in 16% of the recipients. A leucocyte alloimmunization rate of 24% was found. G-CSF stimulation and transfusion of G-CSF-mobilized granulocytes were well tolerated by donors and recipients, respectively.

Transfusion-associated graft vs. host disease (TA-GVHD) is a well-known but rare complication that follows infusion of histo-incompatible lymphoid cells, often seen in individuals with impaired cellular immunity. However, we present here a case report of fatal TA-GVHD in a 'presumed' immunocompetent patient after transfusion of a freshly isolated buffycoat from a relative as part of our protocol to prepare the patient for living-related kidney transplantation. To confirm the diagnosis of TA-GVHD, a polymerase chain reaction was used to detect donor cells in various affected tissues. Furthermore, the immune reactivity of the patient against donor and vice versa was tested on samples taken before transfusion using limiting dilution assays. Our patient received a transfusion with blood from a donor who was homozygous at the human leukocyte antigen (HLA) class I loci. Despite incompatibility for HLA class II, infused donor T lymphocytes were not rejected and became engrafted. The patient did not have cytotoxic T lymphocytes to reject the donor cells. DNA polymorphism studies on several organ biopsies confirmed the presence of infiltrating cells of donor origin. This report illustrates the possibility, in the general patient population, of developing TA-GVHD from whole blood transfusion. In the case of pre-transplant blood transfusion, the patient and donor have to be HLA-typed and special care should be taken in the situation of donor homozygosity for HLA class I, even in the presence of HLA class II incompatibility. Protocols in which donor-specific blood or bone marrow transfusions are given in an attempt to modulate the immune system should exclude these combinations.