Tabarean wrote: "Histamine modulates several aspects of energy homeostasis. By activating histamine receptors in the hypothalamus the bioamine influences thermoregulation, its circadian rhythm, energy expenditure and feeding. These actions are brought about by activation of different histamine receptors and/or the recruitment of distinct neural pathways." Wondering if this could also be a description of cancer cachexia in neurobiological terms, Zwickl began scouring the literature, pondering possible mechanisms involved, checking plausibility, looking at phenomena where distinct mechanisms have already been shown, and eventually coming up with what is being presented in this paper.

Myeloproliferative neoplasms (MPN), classified as polycythemia vera (PV), essential thrombocytosis (ET) and myelofibrosis (MF) are stem-cell derived disorders. Mutations in either the januskinase-2 (JAK-2) or the calreticulin (CALR) gene are characteristic for MPN and may result in enhanced proliferation of red blood cells, white blood cells and platelets, and thus increase the risk for vascular events.This study is a retrospective and descriptive analysis of records of patients, who underwent treatment for myeloproliferative syndromes at the Department of Hemato-Oncology of the University hospital Krems from 2008 to the end of 2015. Out of 250 patients, who were suspected for MPN, 51 patients displayed a JAK-2 V617F mutation. These were analyzed with regard to their blood values, gender, age at diagnosis, therapy and vascular events before and after diagnosis (during therapy). Of the 51 patients diagnosed with MPN and a JAK-2 V617F mutation, 33 suffered from PV, 15 from ET and 3 from MF. More men than women were diagnosed with MPN and the median age at diagnosis was 72 years. Acetylsalicylic acid, phlebotomy and Hydroxyurea were the most frequent therapies applied. In our study cohort, the most common vascular events were acute coronary syndrome and transitory ischemic attack. Thromboembolic events were effectively reduced by MPN therapy while no elevation in bleeding events could be observed.

Cancer cachexia is characterized by the impairment of glucose and lipid homeostasis, the acceleration of processes promoting the mobilization of energy-rich compounds (e.g., insulin resistance, gluconeogenesis, and lipolysis) and the simultaneous activation of highly energy-demanding processes (e.g., systemic inflammation and activation of brown adipose tissue). We hypothesized that these processes might themselves change during cancer cachexia progression, such that plasma levels of glucose and lipids might be used to distinguish between the non-malignant state, pre-cachexia and cachexia. We performed an initial cross-sectional study including 60 treatment naïve cancer patients (38 with cancer cachexia and 22 with cancer pre-cachexia) and 61 patients without malignancy (21 with metabolic syndrome and 40 controls). Differences in lipids (total cholesterol, LDL and HDL cholesterol) and plasma fasting glucose were analyzed across various group configurations, with adjustments to age and antidiabetic or lipid-lowering drugs. Our study showed that levels of LDL cholesterol and total cholesterol might indicate cachexia stages irrespective of the presence of metabolic syndrome or lipid-lowering medication. High levels of plasma glucose were only seen in cachectic cancer patients on antidiabetics. These observations indicate that markers of metabolic dysregulation associated with cachexia progression might be exploited for early detection of malignancy.

Background & AimIn randomised clinical trials, the type II anti-CD20 antibody obinutuzumab has been shown to be more effective than rituximab for therapy of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). However, this enhanced efficacy was linked with elevated rates of high-grade adverse events. The aim of this study was to assess the tolerability and toxicity profile of obinutuzumab treatment in routine patients with CLL and FL, of whom the majority had experienced toxicity or resistance to rituximab.MethodsThis retrospective cohort study investigated fifteen obinutuzumab-treated patients, eight with CLL and seven with FL. The course of the disease, comorbidities and treatment-related toxicities were recorded. All patients with CLL and all but three FL patients had any form of pre-treatment with rituximab.ResultsBetween October 2014 and August 2017, 15 patients were treated with obinutuzumab at the University Hospital Krems. In the CLL-cohort, 1 patient (12,5%) developed pneumonia, 2 (25%) febrile neutropenia, 6 (75%) anemia and 7 (87,5%) thrombocytopenia, respectively. One patient exhibited an infusion-related allergic reaction. In the FL-cohort, 6 patients (85,7%) presented with thrombocytopenia, 3 (42,9%) with anemia and one patient with neutropenia. No sepsis or consecutive solid tumors were seen in any of the patients.ConclusionObinutuzumab was mostly well tolerated in mild to heavily pre-treated patients with CLL and therapy-naïve or pre-treated patients with FL. The frequency and profile of adverse events and toxicity was comparable to data from previous clinical studies and could be managed adequately in the setting of a University Clinic.

Background Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients. Methods In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio. Results Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis. Conclusions CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and prognostic information is essential in finding the right treatment. This study evaluated the prognostic significance of Ki-67 in patients with DLBCL. Methods: Patients with DLBCL, treated with first-line R-CHOP, were retrospectively analyzed in groups of high (>70%) and low (≤70%) Ki-67. Parameters of interest were the international prognostic index (IPI), treatment response, progression-free survival (PFS) and overall survival (OS). A chi-squared test or Fisher’s exact test was conducted to analyze categorical variables. Kaplan–Meier and log-rank tests were applied for survival analyses. Finally, a multivariate linear regression analysis was performed, including gender, Ki-67 ≤ 70% or >70%, IPI and presence of B symptoms. Results: Overall, 58 patients were included. No significant association was found between Ki-67 status and IPI (p = 0.148) or treatment response (p = 0.373). Survival in patients with high Ki-67 was significantly inferior with respect to OS (p = 0.047) but not PFS (p = 0.138). Multivariate linear regression, however, yielded only IPI as a risk factor for OS. Conclusion: Future studies with larger patient cohorts are needed in order to elucidate the prognostic role of Ki-67 in patients with DLBCL treated with R-CHOP.

The aim of this retrospective study was to evaluate the efficacy and toxicity profile of bendamustine, bortezomib, and dexamethasone (BBD) combination treatment of patients with newly diagnosed multiple myeloma (MM). BBD treatment had a response rate of 80% regarding patients with ≥ partial response (PR). Median time to best response was 87.5 days and PFS was 22 months. Median of OS was not reached. PFS of non-responding patients was significantly shortened compared to those with ≥ PR. No statistically significant differences were determined concerning age (≥ vs. < 68 years) and ISS stage (ISS stage I/II vs. III). Grade 3 hematological effects and grade 3/4 non-hematological effects occurred in 20% and 35% of patients, respectively. Most pronounced hematological adverse event was leukopenia, the most severe non-hematological ones affected the cardiovascular system. In summary, BBD treatment was of acceptable efficacy in patients with newly diagnosed MM and exhibited rather low toxicity.

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