Purpose APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) APR-246. Patients Methods was administered as 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies prostate cancer. Acute myeloid leukemia (AML; n = 7) cancer (n...

We present a comprehensive study of new infectious disease in immune compromised patients, neoehrlichiosis. The clinical picture the can be misleading because symptoms may misinterpreted to worsening underlying disease. Background. Candidatus Neoehrlichia mikurensis is newly discovered noncultivatable bacterium spread among ticks and rodents Europe Asia that infect humans, particularly immunocompromised patients. Methods. compiled laboratory data from 11 patients with hematological...

Summary Chemotherapy and rituximab (R) is current standard therapy in diffuse large B‐cell lymphoma (DLBCL), but a substantial proportion of patients still fail to reach sustained remission. In vitro studies have indicated that resistance could be accompanied by dysregulated apoptotic pathways, such as the phosphatidylinositol 3‐kinase (PI3K)/AKT signaling pathway, which can constitutively activated DLBCL. this retrospective, immunohistochemical study on 106 treated with R‐CHO(E)P...

It remains unknown how the introduction of high-sensitivity cardiac troponin T (hs-cTnT) has affected incidence, prognosis, and use coronary angiographies revascularizations in patients with myocardial infarction (MI). The aim this study was to investigate incidence MI prognosis after a first by hs-cTnT. In cohort study, authors included all from Swedish National Patient Registry 2009 2013. Cox regression used calculate hazard ratios (HRs) 95% confidence intervals (CIs) for risk all-cause...

Methyl-CpG-binding domain protein enriched genome-wide sequencing (MBD-Seq) is a robust and powerful method for analyzing methylated CpG-rich regions with complete coverage. In chronic lymphocytic leukemia (CLL), the role of CpG associated transcribed long noncoding RNAs (lncRNA) repetitive genomic elements are poorly understood. Based on MBD-Seq, we characterized global methylation profile high in different CLL prognostic subgroups based IGHV mutational status. Our study identified 5800...

Summary Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL). To estimate the benefit of these in real‐world setting, comprehensive data on patients treated clinical routine are needed. We report outcomes 736 R/R DLBCL identified among all curatively Sweden period 2007–2014. Survival and associations with disease characteristics, second‐line treatment fulfilment chimaeric antigen receptor (CAR) T‐cell trial criteria...

Summary The prognostic significance of tumour‐infiltrating lymphocytes (TILs) in patients with diffuse large B‐cell lymphoma (DLBCL) remains controversial. Furthermore, the possible impact regulatory T cells (T regs ) on survival DLBCL is still unknown. We performed a retrospective study immunohistochemical expression cytotoxic and , their correlation 195 patients. Patients small number T‐cell intracytoplasmic antigen‐1 (TIA‐1)+ (≤260 cells/mm 2 tumour area; n = 52) had significantly better...

Tumor-associated macrophages (TAM) have been ascribed both pro- and anti-tumor properties, but the majority of clinical cancer studies shown that presence a high number TAM is related to poor prognosis, suggesting predominantly exert pro-tumoral activity. The prognostic role in patients with diffuse large B-cell lymphoma (DLBCL), however, so far unknown. Therefore, were immunohistochemically stained CD68 antibody retrospective, population-based study including 176 DLBCL treated curative...

Idiopathic thrombocytopenic purpura (ITP) is an organ specific autoimmune disorder in which T-lymphocyte abnormalities have pathogenetic importance. In a DNA microarray screen of CD3+ T-lymphocytes from ITP patients and healthy controls we found altered expression genes associated with apoptosis, e.g. A20, caspase-8 Bax. This together our previous findings increased gene Fas, interferon-g IL-2 receptor beta (IL2RB) indicated activation induced cell death (AICD) T-cells ITP. Using...

Chronic lymphocytic leukemia (CLL) can be divided into prognostic subgroups based on the IGHV gene mutational status, and is further characterized by multiple subsets of cases with quasi-identical or stereotyped B cell receptors that also share clinical biological features. We recently reported differential DNA methylation profiles in IGHV-mutated IGHV-unmutated CLL subgroups. For first time, we here explore global different prognosis, applying high-resolution arrays samples from three major...

The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients a well-defined geographic area: Sweden. All diagnosed with CLL (2007–2013) (n=3672) were identified from national registries, screening patient files all (100%) treated first line (n=1053) and for those, an in-depth analysis performed. End points overall response rate, progression-free survival (PFS), (OS), safety. Median age 71 years; 53% had Rai...

The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated (ABC). Gene expression profiling (GEP) is preferably used determine the cell of origin (COO). However, GEP not widely applied clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was evaluate concordance COO assignment between Lymph2Cx assay IHC-based Hans algorithm, decide which model...

Summary. Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which activated T‐helper (Th) cells and different Th‐cell cytokines might play important role. We have recently reported that chronic ITP patients remission had elevated plasma levels of the Th3 cytokine transforming growth factor‐β1 (TGF‐β1), possibly as a part bystander immune suppression. In present study we found that, with active disease [platelet count (plc) < 50 × 10 9 /l], mitogen‐stimulated...

The prognostic role of overexpression Ki-67 protein in diffuse large B-cell lymphoma (DLBCL) is still unclear. Furthermore, immunohistochemical studies have suggested a correlation between markers proliferation, differentiation and apoptosis, but the relevance these findings has not been clarified. To investigate impact Ki-67, context this correlation, retrospective study was performed on 199 DLBCL patients treated with curative intent. Patients low expression (<49%) had significantly worse...

Patients with chronic lymphocytic leukemia (CLL) have impaired response to vaccination, which calls for improved vaccination strategies. This study aimed evaluate antibody persistence five years after pneumococcal and revaccination. Seventyfour CLL patients 31 controls, all primary immunized 13-valent conjugated vaccine (PCV13) or 23-valent polysaccharide (PPSV23), were included. Antibody was assessed, followed by revaccination PCV13 a second PPSV23. Serological protection (SP), defined as...

In acute myeloid leukemia with NPM1 mutation, analysis of measurable residual disease (MRD) reverse transcription quantitative polymerase chain reaction (RT-qPCR) is recommended for response assessment and monitoring after treatment. For rare mutations in NPM1, this not readily available. Therefore, we evaluated the prognostic value deep sequencing covering all exon 11 variants, using retrospectively analyzed bone marrow samples from 97 patients remission during MRD positivity was defined as...

Abstract The location of the carotenoid 2A g ‐state (S 1 ) was studied by fluorescence spectroscopy in two series carotenoids. One consisted natural polyenes like phytoene, phytofluene, β‐carotene, and neurosporene, other minicarotenes, i.e., compounds similar to but with a smaller number double bonds (n =3–9). A decrease S ‐S 0 energy gap n observed both series, extrapolation = 11 gave energies 14 500 13 200 cm −1 for β‐carotene lycopene, respectively. neurosporene state located at ca 16...

AbstractMost studies concerning therapy and prognosis in diffuse large B-cell lymphoma (DLBCL) are based on highly selected patient material. To evaluate treatment, clinical prognostic factors, outcome a population-based cohort, we performed retrospective study comprising 535 de novo DLBCL patients western Sweden, diagnosed between 1995 2000. The median age was 73 years. Treatment with curative intent administered to 376 (70%) patients. International Prognostic Index (IPI) strongly predicted...

// Olle Werlenius 1,2 , Johan Aurelius Alexander Hallner 2 Ali A. Akhiani Maria Simpanen Anna Martner Per-Ola Andersson 3 Kristoffer Hellstrand and Fredrik B. Thorén 1 Department of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden TIMM Laboratory, Cancer Center, Medicine, Södra Älvsborgs Borås, Correspondence to: Thorén, email: Keywords : monoclonal antibodies, reactive oxygen species, immunotherapy, NK cells, NOX2 Received March 31, 2016 Accepted April 03, Published 16,...

Summary Routine follow‐up for diffuse large B‐cell lymphoma have been shortened to 2 years when event‐free survival at 24 months (EFS24) emerged as a new milestone. In the present study, we aimed determine whether achievement of this milestone affected overall (OS). We compared OS that an age‐ and sex‐matched population, analysed other factors governing OS, reviewed causes death. Data were collected from Swedish Cancer Registry individual patient’s records. included 1169 adult patients five...