Basophil activation test for allergic and febrile non-haemolytic transfusion reactions among paediatric patients with haematological or oncological disease.

BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are common, although their mechanisms remain unclear. Immunoglobulin E (IgE)-mediated type I hypersensitivity may be involved in the pathogenesis of ATR. A basophil activation test (BAT) may help elucidate this process. MATERIALS AND METHODS: The BAT was based on peripheral blood samples from paediatric patients with a haematological or oncological disease and on samples of residual blood products transfused in each case. Dasatinib was used to evaluate whether basophil activation was mediated by an IgE-dependent pathway. RESULTS: Twenty-seven patients with and 19 patients without ATR/FNHTR were included in this study, respectively. The median BAT values associated with ATR- (n = 41) and FNHTR-causing (n = 5) blood products were 22.1% (range = 6.1%-77.0%) and 27.8% (range = 15.2%-47.8%), respectively, which were higher than the median value of 8.5% (range = 1.1%-40.9%) observed in blood products without a transfusion reaction. Dasatinib suppressed basophil activity. BAT values were comparable in patients with ATR regardless of severity. Meanwhile, BAT values analysed with blood products non-causal for ATR/FNHTR were higher in patients with ATR/FNHTR than in those without. CONCLUSION: The IgE-mediated type I hypersensitivity may be involved in the pathogenesis of ATR and FNHTR. BAT analyses may help elucidate the underlying mechanisms and identify patients at risk.

Investigation of patient factors associated with the number of transfusions required during chemotherapy for high-risk neuroblastoma.

BACKGROUND: Blood transfusion is an important supportive care for high-risk neuroblastoma. When the number of transfusions increases, transfusion-associated adverse reactions may be more problematic. However, the factors determining the degree of myelosuppression and the number of transfusions during chemotherapy for high-risk neuroblastoma remain unclear. MATERIALS AND METHODS: We investigated patient factors determining the number of required transfusions in 15 high-risk neuroblastoma patients who received five courses of chemotherapy. Clinical data, cytokine profile and colony-forming assay with bone marrow samples at diagnosis were analysed. RESULTS: The required number of transfusions of both platelets and erythrocytes decreased once in the second course and then increased as the course progressed. The variability among cases increased as the chemotherapy course progressed. In cases of low peripheral blood platelet count and lower fibrinogen level at diagnosis, the number of platelet transfusions was higher during chemotherapy. In contrast, there was a negative correlation between the forming ability of granulocyte-macrophage or erythroid colonies and the number of erythrocyte transfusions in the latter period. CONCLUSION: In the early stages of chemotherapy, bone marrow infiltration in neuroblastoma and/or coagulopathy complication may cause thrombocytopenia and requirement of platelet transfusion; conversely, in the later stages, the number of erythrocyte transfusions may be defined by the patient's inherent hematopoietic ability. These factors may be useful in predicting the required number of transfusions.

Predictive factors of poor blood collecting flow during leukocyte apheresis for cellular therapy.

Leukocyte apheresis is necessary in various cellular therapies. However, maintenance of a stable flow rate during leukocyte apheresis is often difficult, even in patients or donors without major problems. Despite this, predictive methods and evidence regarding the reality of the situation are limited. We conducted a retrospective analysis involving adult patients who required leukocyte apheresis for the treatment of neoplasms using WT1-pulsed dendritic cell vaccine. Monocytes were separated from apheresis products to obtain dendritic cells. All the patients were pre-evaluated based on laboratory and chest X-ray findings and subjected to an identical apheresis procedure. The occurrence of poor blood collecting flow during leukocyte apheresis was monitored, and the frequency, clinical information, and associated risk factors were analyzed. Among 160 cases, poor blood collecting flow was observed in 53 cases (33.1%) in a median time of 54 min (range, 2-127 min) post-initiation of leukocyte apheresis. Owing to difficulty in obtaining higher collecting flow, a longer procedure time was required, and in some cases, the scheduled apheresis cycles could not be completed. Consequently, the number of harvested monocytes was low. Multivariable analysis indicated that female patients have an increased risk of poor inlet flow rate. Furthermore, prolonged QT dispersion (QTD) calculated using Bazett's formula was found to be a risk factor. Although the patients did not present any major problems during leukocyte apheresis, poor blood collecting flow was observed in some cases. Sex and pre-evaluated QTD might be useful predictors for these cases; however, further prospective evaluation is necessary.

Inorganic Iron Supplementation Rescues Hematological Insufficiency Even Under Intense Exercise Training in a Mouse Model of Iron Deficiency with Anemia.

Iron deficiency anemia (IDA) due to malnutrition and/or blood loss is a common condition, especially in women of reproductive age. Intense exercise can induce anemia via an inflammatory response, but whether intense exercise affects the efficacy of iron supplementation to treat IDA is unclear. Here, we show in a mouse model of IDA that acute intense swimming increased IL-6 levels in the blood, but did not affect the maximum elevation of plasma iron following oral administration of 0.5 mg/kg Bw iron. However, compared with the control group without intense exercise, acute intense swimming was associated with a significant decrease in plasma iron 2 and 4 h after iron loading that could be attributed to rapid iron absorption in peripheral tissues. In the chronic experiment, IDA mice administered 0.36, 1.06, or 3.2 mg/kg Bw iron per day that were subjected to 11 intense swimming sessions over 3 weeks showed significantly decreased recovery levels for hemoglobin and red blood cell count during the early phase of the experimental period. At the end of the experimental period, significant, dose-dependent effects of iron, but not the main effect of intense exercise, were seen for recovery of hemoglobin and red blood cell counts, consistent with the acute exercise study. These results suggested that intense exercise in the presence of IDA does not inhibit iron absorption from the gastrointestinal tract and that iron supplementation can enhance the recovery process even after intense exercise.

Transfusion outcome for volume- and plasma-reduced platelet concentrates for pediatric patients.

BACKGROUND AND OBJECTIVES: Plasma reduction in platelet concentrate (PC) products has been reported to prevent large volume load and transfusion-related adverse reactions (TRARs). However, volume reduction might be associated with a poor transfusion response because of a deterioration in platelet (PLT) quality. Because PLT quality control and transfusion responses for recently washed PCs using PLT additive solutions are superior, we investigated the clinical safety and transfusion efficacy of volume-reduced washed PCs in pediatric patients. MATERIALS AND METHODS: We prepared a simplified resuspended PC product (RPC) as a washed PC. Regular RPC (R-RPC) included equivalent volumes of bicarbonate Ringer's solution and anticoagulant citrate dextrose solution A (BRS-A) as the resuspension solution. Half RPC (H-RPC) was prepared by adding a half volume of BRS-A. Twenty-four pediatric patients were scheduled for transfusions with R-RPC and H-RPC up to 4 times. R-RPC was transfused 42 times into 24 patients. H-RPC was transfused 41 times into 23 patients. RESULTS: Neither product was observed to cause TRARs. Although the calculated PLT recovery for H-RPC was significantly reduced, the posttransfusion corrected count increment (24 h) did not differ. Moreover, similar results were observed for vital signs during transfusion. CONCLUSION: Volume-reduced washed PC can be transfused without causing TRARs, differences in vital signs, or inferior transfusion responses. Volume-reduced washed PC also provides the advantages of shortened transfusion times and reduced volume loads. Although a standard technique for stable resuspension is necessary, volume-reduced washed PC may be a beneficial option for children, including neonates, or individuals with cardiovascular or renal problems.

Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8+ T Cells.

The thymoproteasome subunit ß5t is specifically expressed in cortical thymic epithelial cells (TECs) and generates unique peptides to support positive selection. In this study, using a mouse model ubiquitously expressing ß5t, we showed that aberrant expression of self-peptides generated by ß5t affects CD8+ T cell homeostasis, including thymic selection and maintenance of the peripheral naive pool of CD8+ T cells. In mice in which ß5t was expressed both in cortical and medullary TECs, the abundance of CD8+ lineage thymocytes was reduced, and extra-thymic expression of ß5t caused accumulation of CD8+ T cells with the memory or exhausted phenotype and induced autoreactive T cell responses. We found that thymoproteasomes are essential for positive selection but that the subsequent change in peptide repertoire in the medulla is also crucial for thymic selection and that ß5t-derived peptide must be confined to the thymus to avoid autoimmunity in peripheral tissues.