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Allogeneic hematopoietic cell transplantation (HCT) can be curative for acute myeloid leukemia (AML). Novel therapies may render patients' bone marrow hypocellularity and lead to prolonged post-therapy pancytopenia. Patients' bone marrow cellularity (BMC) at pretransplant assessment and post-treatment pancytopenia (classification CR-incomplete [CRi]) may manifest AML persistence.
We retrospectively examined the impact of BMC and ELN response (ELNr) on a single-center cohort of 337 patients who underwent allogeneic HCT for AML in CR1.
Median follow-up was 33months. Overall survival (OS) for the whole cohort was 55.8% at 2years, while cumulative incidence of relapse (CIR) was 20.8%, and non-relapse mortality was 27.5%. OS and CIR were not significantly different between BMC groups; and neither was ELNr. ELNr CRi was associated with BMC aplastic and hypocellular marrow states (P<2.6e-8). Multivariate analysis confirmed neither BMC nor attainment of ELNr CR vs CRi affected OS or relapse. Significant factors for survival included age at transplant, cytogenetic risk, development of acute Gr II-IV GvHD, and moderate-severe chronic GvHD, while cytogenetic risk and chronic GvHD affected relapse.
Neither ELNr status nor pretransplant BMC influenced relapse post-HCT or OS. Hypocellularity and CRi are not negative prognostic factors for post-HCT outcomes of AML.
Neither ELNr status nor pretransplant BMC influenced relapse post-HCT or OS. Hypocellularity and CRi are not negative prognostic factors for post-HCT outcomes of AML.Attachment of a pair of P-stereogenic mesityl(alkynyl)phosphanyl groups at the 4- and 5-positions of a 9,9-dimethylxanthene framework gave mixtures of the respective rac- and meso-bisphosphanyl diastereoisomers. They slowly epimerized in a thermally induced reaction with Gibbs activation barriers of about 25 kcal mol-1 at room temperature (measured and DFT calculated). The reaction of the meso-mesityl(tert-butylethynyl)phosphanyl derivative with two molar equivalents of Piers' borane [HB(C6 F5 )2 ] led to the formation of the alkylidene-bridged geminal bisphosphane/borane-frustrated Lewis pair system. The compound was obtained enriched (>85 %) in the rac diastereoisomer. With a variety of bifunctional donor substrates, the rac-bis-P/B FLP formed macrocyclic compounds. They were all formally derived from meso-configurated diastereoisomers of the bisphosphanylxanthene backbone.Breeding strategies for smallholder dairy farming systems in Sub-Saharan Africa (SSA) were simulated and evaluated considering cow traits identified as priorities by farmers in different agro-ecological zones. These traits were related to cow milk yield, fertility, temperament, feed intake and disease resistance. The first breeding strategy was based on continuous importation of genetically superior exotic dairy sire semen to SSA and crossing with local females leading to a gradual upgrade of the indigenous population. The second strategy assumed that semen from elite exotic bulls would be imported to SSA and used on indigenous cows to produce F1 animals. Thereafter, elite animals would be selected from within the F1 and each subsequent generation to establish a new synthetic breed. The third strategy was to improve the indigenous population by genetically selecting the best sires available domestically. Results showed positive genetic progress for all breeding goal traits. After 15 generations of selection, the genetic response of the importation strategy exceeded the corresponding genetic response of the synthetic breed strategy by 20%-60%. The former also exceeded the genetic response of the indigenous breed improvement strategy by 43%-75%. Potentially there is an opportunity for breeders to choose an appropriate breeding strategy that fits a specific need of smallholder dairy farmers.We previously showed that noninvasive mild ischemia (preconditioning; PC) induced ischemic tolerance by upregulation of P2X7 receptors in astrocytes via a hypoxia inducible factor-1α (HIF-1α)-dependent mechanism. The P2X7 receptor is known as a low-sensitivity P2 receptor that requires a high extracellular ATP (eATP) concentration for activation. PC increased the eATP level but was not sufficient to activate P2X7 receptors. Here, we show that astrocytes possess an elaborate mechanism for activation of P2X7 receptors, thus contributing to ischemic tolerance. Nicotinamide adenine dinucleotide (NAD+ ) was shown to increase the sensitivity of P2X7 receptors to eATP via ecto-ADP-ribosyltransferase 2 (ARTC2)-catalyzed ADP-ribosylation in peripheral immune cells. Although ARTC2-positive signals were mostly absent in the naïve brain, they were selectively increased in astrocytes by PC. The spatiotemporal pattern of PC-evoked ARTC2 was well associated with that of P2X7 receptors. In the in vitro experiments, NAD+ increased the sensitivity of P2X7 receptors to ATP, and at higher concentrations, NAD+ itself activated P2X7 receptors without eATP in cultured astrocytes. In the in vivo experiments using middle cerebral artery occlusion model mice, the PC-evoked increase in HIF-1α in astrocytes was abolished by the ARTC2 inhibitor S + 16a. S + 16a also abolished PC-evoked ischemic tolerance. Taken together, the results suggested that P2X7 receptors can be sensitized to ATP by NAD+ /ARTC2-catalyzed ADP-ribosylation, which allows astrocytes to drive P2X7 receptor-mediated ischemic tolerance even though PC only slightly increases the amount of eATP.Human cytomegalovirus (HCMV) is a common cause of significant morbidity and mortality in transplant recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). selleckchem We evaluated interferon-γ (IFN-γ) secretion by HCMV NLV-specific CD8+ T cells in HCMV-reactivated allo-HSCT recipients using an enzyme-linked immunospot (ELISPOT) assay at 3 months post-transplantation. Blood samples from 47 recipients were tested for HCMV DNAemia, HCMV pp65 antigenemia, and anti-HCMV immunoglobulins (IgG/IgM) over 3 months post-transplantation. Of the 47 transplant recipients, 26 were HLA-A*02 positive and 21 were HLA-A*02 negative. The results were essentially consistent between the 47 transplant recipients and the HLA-A*02-positive recipients. HCMV DNAemia was not linearly correlated with IFN-γ spot-forming cells (SFCs) counts; IFN-γ SFCs counts did not differ significantly between the HCMV DNAemia-positive and -negative groups, whereas the HCMV-DNA virus loads were inversely correlated with the IFN-γ SFCs counts.
Read More: https://www.selleckchem.com/products/fadraciclib.html
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