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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.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.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.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.

Background Leukoreduced blood components have been widely implemented to prevent transfusion-transmitted cytomegalovirus (TT-CMV) in transplantation. Recent progress in leukoreduction technology has helped reduce the risk of TT-CMV in hematopoietic stem cell transplantation; however, its efficacy in umbilical cord blood transplantation (CBT) has not been systematically studied. Study design and methods We retrospectively analyzed the incidence of CMV infection in patients treated with CBT who received prestorage leukoreduced, CMV-unselected blood components between 2007 and 2017 in a single Japanese pediatric center. Patients were monitored for CMV antigenemia at least once weekly. Results In total, 71 patients treated with CBT were identified. Two patients were excluded because of unknown CMV serostatus or early death after CBT. Of the remaining 69 patients, 24 developed CMV antigenemia. Among them, 3 received granulocyte transfusions (3 of 3; 100%), 2 were infants with severe combined immunodeficiency who had been infected with CMV before CBT (2 of 2; 100%), and 19 were CMV-seropositive patients (19 of 23, 82.6%). Conversely, of the remaining 45 patients in whom CMV antigenemia did not develop, 41 were seronegative (0 of 41; 0%) and were transfused with a total of 925 leukoreduced, CMV-unselected blood components. Among the 41 patients, 9 (22%) received in vivo T-cell depletion with antithymocyte globulin. None of the patients in the seronegative group has subsequently shown evidence of CMV infection or developed CMV disease. Conclusion Using prestorage leukoreduction, no cases of CMV infection were detected in seronegative CBT patients. Our findings showed the safety of leukoreduction in preventing TT-CMV in this patient group.

Mechanisms of relapse of acute lymphoblastic leukemia (ALL) after human leukocyte antigen (HLA) class II mismatched hematopoietic stem cell transplantation (HSCT) remain unclear. We report two children with relapsed ALL after HSCT from related donors with HLA-DRB1 and -DQB1 mismatches in the graft versus host direction. One lost HLA-DRB1, DQB1, and DPB1 alleles, and the other lost one HLA haplotype of the leukemic blasts at relapse. HLA class II loss may be a triggering event for ALL relapse after partially HLA-mismatched-related HSCT. In addition, HLA typing of relapsed leukemic blasts could be vital in the selection of retransplant donors.

Background Encouraging responses to histone deacetylase inhibitors have been reported for hematologic malignancies. Here, we report effects of panobinostat and 5-azacytidine on the proliferation of juvenile myelomonocytic leukemia (JMML) CD34+ cells. Procedure We previously reported that stimulation of JMML CD34+ cells with stem cell factor and thrombopoietin on irradiated murine AGM-S3 cells led to substantial expansion of JMML CD34+ cells that contained leukemic stem cells capable of transplantation into immunodeficient mice. Using this culture system, we evaluated effects of panobinostat and 5-azacytidine on the proliferation of JMML CD34+ cells. Results Panobinostat dose dependently reduced the numbers of day 7 CD34+ cells generated under stimulation of hematopoietic growth factors on AGM-S3 cells in all eight patients with JMML. These patients possessed various genetic and/or karyotypic abnormalities. CD34+ CD38- cells were substantially more sensitive to panobinostat at 10 and 20 nM than CD34+ CD38+ cells. Panobinostat, however, failed to influence the ability of AGM-S3 cells to stimulate JMML CD34+ cell production. In contrast to HL60 cells, apoptosis and cell cycle arrest in panobinostat-mediated inhibition were at low levels in JMML. The inhibitor also suppressed the factor-dependent proliferation of normal CD34+ cells on AGM-S3 cells. Meanwhile, no substantial inhibitory effects of 5-azacytidine on the growth of JMML CD34+ cells were observed. Conclusions These results demonstrate that panobinostat directly suppresses the growth of JMML CD34+ cells, in particular CD34+ CD38- cells, regardless of the genetic abnormality type, suggesting that it is a useful antileukemic drug to target JMML stem cells at a pretransplant stage.

An N-phenylcarbazole-containing poly(p-phenylenevinylene) (PPV), poly[(2-(4′-carbazol-9-yl-phenyl)-5-octyloxy-1,4-phenylenevinylene)-alt-(2-(2′-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene)] (Cz-PPV), was synthesized, and its optical, electrochemical, and electroluminescent properties were studied. The molecular structures of the key intermediates, the carbazole-containing boronic ester and the dialdehyde monomer, were crystallographically characterized. The polymer was soluble in common organic solvents and exhibited good thermal stability with a 5% weight loss at temperatures above 420 °C in nitrogen. A cyclic voltammogram showed the oxidation peak potentials of both the pendant carbazole group and the PPV main chain, indicating that the hole-injection ability of the polymer would be improved by the introduction of the carbazole-functional group. A single-layer light-emitting diode (LED) with a simple configuration of indium tin oxide (ITO)/Cz-PPV (80 nm)/Ca/Al exhibited a bright yellow emission with a brightness of 1560 cd/m2 at a bias of 11 V and a current density of 565 mA/cm2. A double-layer LED device with the configuration of ITO/poly(3,4-ethylenedioxy-2,5-thiophene):poly (styrenesulfonic acid) (60 nm)/Cz-PPV (80 nm)/Ca/Al gave a low turn-on voltage at 3 V and a maximum brightness of 6600 cd/m2 at a bias of 8 V. The maximum electroluminescent efficiency corresponding to the double-layer device was 1.15 cd/A, 0.42 lm/W, and 0.5%. The desired electroluminescence results demonstrated that the incorporation of hole-transporting functional groups into the PPVs was effective for enhancing the electroluminescent performance. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5765–5773, 2005