Lenalidomide in combination with dexamethasone: effective regimen in patients with relapsed or refractory multiple myeloma complicated by renal impairment

Over the past decade, treatment options for patients with multiple myeloma (MM) have improved substantially, resulting in better response rates and prolonged overall survival (OS). Nevertheless, MM remains a challenging disease, especially if renal insufficiency (RI) or extensive pre-treatment aggravates the assignment of the optimal treatment schedule. In this retrospective study, we analyzed the outcome of lenalidomide plus dexamethasone in 167 patients with relapsed or refractory MM with focus on RI. The baseline creatinine clearance (CL_Cr) was normal in 94 patients (CL_Cr ≥ 80 ml/min), while RI was observed in 73 patients, including 40 patients with mild RI (50 ≤ CL_Cr < 80 ml/min) and 33 patients with moderate or severe RI (CL_Cr < 50 ml/min). Response rates declined depending on the severity of RI, being 67% among patients with normal kidney function, 60% among patients with mild RI and 49% among patients with moderate or severe RI. Time to progression (TTP) was significantly reduced in patients with severe RI and in case of >2 previous treatment lines. OS was not significantly different between patients with normal and impaired renal function. In contrast, the number of previous treatment lines (2 vs. <2) and the use of novel agents like bortezomib or thalidomide prior to lenalidomide plus dexamethasone therapy had a more adverse effect on OS. In conclusion, lenalidomide plus dexamethasone is an effective regimen for relapsed or refractory patients with MM complicated by RI with manageable toxicity.     

Vascular Endothelial Growth Factor Levels in Childhood Acute Lymphoblastic and Myeloblastic Leukemia

Angiogenesis has been associated with the growth, dissemination and metastasis and has been shown to be a prognostic. Although there are some data suggesting that angiogenesis may have a role in the pathophysiology of leukemia, its role in patient prognosis is yet to be defined. We analyzed the expression level of vascular endothelial growth factor (VEGF), an angiogenesis promoter and its possible- prognostic value in bone marrow samples at the time of diagnosis and remission of acute childhood leukemia patients. Besides 46 patients diagnosed as ALL or AML, 16 children were also included as a control group in the study. Our data have demonstrated that VEGF levels of AML patients were found higher than the control group statistically (P = 0.022). However we could not find any significant difference between VEGF levels of diagnosis and remission in both AML and ALL groups by blastic VEGF expression (P > 0.05). In this study the higher levels of VEGF in AML patients is one of the main findings although we were not able to assess any role of VEGF in predicting prognosis in pediatric leukemia patients by evaluating blastic cell VEGF expression. These results have demonstrated that the relationship between angiogenesis or angiogenesis promoters and hematological malignancies is not clear and simple as different methods or different cells beside different angiogenesis promotors are involved to these studies. So that not only tumor cells and their cytokines but also surrounding cells and their cytokines must be taken into consideration with the standardized study methods in the further studies to obtain a promising treatment approach.     

A boy with a one-sided red rash

We report on a boy with a sudden onset of unilateral skin lesions following tonsillar infection with fever 2 weeks before. The lesions consisted of erythematous macules with scaling affecting trunk, axillar, as well as inguinal region. CRP, blood differential, serum IgG and IgM antibodies (coxsackievirus, cytomegalovirus, parvovirus, herpes virus, varicella zoster virus, human herpesvirus-6/-7), and lesional swabs (bacteria, dermatophytes, yeasts) were uneventful.     

Generic Anti-PEG Antibody Assay on ProterixBio’s (Formerly BioScale) ViBE Platform Shows Poor Reproducibility

PEGylation is a modification commonly used to increase the half-life of therapeutic proteins. The strategy for immunogenicity testing of these compounds should include methods to detect both anti-protein and anti-PEG antibodies. We previously reported a method for the detection of anti-PEG antibodies using ProterixBio’s (formerly BioScale) acoustic membrane microparticle (AMMP) technology. Our initial method development work showed the assay was capable of detecting antibodies in human serum with a sensitivity of 1 μg/mL with good reproducibility (CV?<?7%). Since the publication of this initial paper, additional experimentation was performed in an effort to validate the assay for support of clinical sample analysis. This additional data indicate that the method has high variability (CV%?>?20) and is unsuitable to support clinical sample analysis.     

A novel approach for acoustic estimation of neck fluid volume between men and women

Obstructive Sleep apnea can be caused by fluid shift from the legs to the neck that narrows the upper airway (UA) and contributes to changes in tracheal sound. Tracheal sound is generated from the turbulent airflow in the pharynx and respiratory airways and it has recently been used to estimate increases in neck fluid volume (NFV). However, tracheal sound is also highly variable among people, especially across the sexes. In this paper, a novel method is proposed to select tracheal sound features towards estimating NFV in men and women separately. To validate this method, it was applied to the tracheal sound data of 28 healthy individuals. Our proposed feature selection algorithm is based on sparse representations and incorporates NFV to maximize the relevance of selected features. This feature selection eliminates the dependence of the previous methods on calibrating the model for every individual. Two models, regression and Kalman filters, are then used to estimate NFV from selected features. Kalman filter obtains the highest performance, estimating NFV with more than 90% accuracy in both men and women. This algorithm can be used to develop non-invasive acoustic technologies to investigate the effects of fluid on UA anatomy in general applications. These results could be used to develop convenient devices to monitor the neck edema and its contribution to sleep apnea severity in fluid retaining patients such as heart or renal failure.     

Incognito: Are Microchimeric Fetal Stem Cells that Cross Placental Barrier Real Emissaries of Peace?

Chimerism occurs naturaly throughout gestation and can also occur as a consequence of transfusion and transplantation therapy. It consists of the acquisition and long-term persistence of a genetically distinct population of allogenic cells inside another organism. Previous reports have suggested that feto-maternal microchimerism could exert a beneficial effect on the treatment of hematological and solid tumors in patients treated by PBSCT. In this review we report the mechanism of transplacental fetal stem cell trafficking during pregnancy and the effect of their long-term persistence on autoimmunity, GVHD, PBSCT, cancer and stem cell treatment.     

Investigating the Dimensions of Youth Wellbeing: An Exploratory Structural Equation Modelling Approach Applied to Palestine

This paper illustrates the “Sen-Nussbaum-type” capability approach to the measurement of youth wellbeing using the newly developed Exploratory Structural Equation Modelling (ESEM). It offers insights into how the capability to achieve wellbeing can be measured in a conflict-affected and resource-constrained setting. The methodology is applied to nationally representative data taken from the Palestinian Family Survey. The population of interest is youth aged 15 to 29. Three capability dimensions are identified: health awareness, knowledge and living conditions. Results show an interrelation between capability dimensions. It is especially important to note the effect of knowledge capabilities on both health awareness and living conditions indicators. Results also confirm the importance of some (exogenous) factors such as the education of the household head in the conversion of capabilities into achievements. Capabilities are shown to be highest in the West Bank for both knowledge and living conditions compared to the Gaza Strip.     

Elevated Plasma S100B,Psychotic Symptoms,and Cognition in Schizophrenia

S100B is a calcium binding protein mainly produced by glial cells. Previous studies have shown elevated levels of S100B in patients with schizophrenia. We measured S100B levels in fasting plasma of 39 patients with schizophrenia and 19 adult healthy controls. We used linear regression to compare S100B between patients and controls. In patients only, we also investigated the relationship between S100B levels and psychotic symptoms (assessed by the Positive and Negative Syndrome Scale), and cognitive function (assessed by the NIH Toolbox Cognition Battery), respectively by calculating Pearson’s correlation coefficients. Mean plasma S100B was significantly higher in the patient group than in the control group. There were no significant correlations between plasma S100B and psychotic symptoms or cognition.     

Statistical and regulatory considerations in assessments of interchangeability of biological drug products

When the patent of a brand-name, marketed drug expires, new, generic products are usually offered. Small-molecule generic and originator drug products are expected to be chemically identical. Their pharmaceutical similarity can be typically assessed by simple regulatory criteria such as the expectation that the 90 % confidence interval for the ratio of geometric means of some pharmacokinetic parameters be between 0.80 and 1.25. When such criteria are satisfied, the drug products are generally considered to exhibit therapeutic equivalence. They are then usually interchanged freely within individual patients. Biological drugs are complex proteins, for instance, because of their large size, intricate structure, sensitivity to environmental conditions, difficult manufacturing procedures, and the possibility of immunogenicity. Generic and brand-name biologic products can be expected to show only similarity but not identity in their various features and clinical effects. Consequently, the determination of biosimilarity is also a complicated process which involves assessment of the totality of the evidence for the close similarity of the two products. Moreover, even when biosimilarity has been established, it may not be assumed that the two biosimilar products can be automatically substituted by pharmacists. This generally requires additional, careful considerations. Without declaring interchangeability, a new product could be prescribed, i.e. it is prescribable. However, two products can be automatically substituted only if they are interchangeable. Interchangeability is a statistical term and it means that products can be used in any order in the same patient without considering the treatment history. The concepts of interchangeability and prescribability have been widely discussed in the past but only in relation to small molecule generics. In this paper we apply these concepts to biosimilars and we discuss: definitions of prescribability and interchangeability and their statistical implementation; the relation between bioequivalence and interchangeability for small-molecule drug products; regulatory requirements and expectations of biosimilar products in various jurisdictions; possible statistical approaches to establish the similarity and interchangeability of biologic drug products; definition of other technical terms such as switchability and automatic substitution. The paper will be concluded with a discussion of the anticipated future use of interchangeability of biological drug products.