Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer

Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3–4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed “per cycle” incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel.The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis.“Per cycle” incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86–0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34–0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86–1; P = 0.07). Patients with a body surface area >2 m² presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86–1; P = 0.07), but decreased odds of having G3 to 4 anemia.Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment.     

A rapid method for obtaining mesenchymal stem cells and platelets from bone marrow aspirate

Mesenchymal stem cells (MSCs) and platelet‐rich plasma (PRP) are currently used alone or in combination for therapeutic applications especially for bone repair. We tested whether MSCs can be isolated from bone marrow (BM) aspirate using a commercially available kit commonly used to obtain PRP from peripheral blood (PB). Results revealed that mononuclear cells and platelets from both PB and BM could be efficiently isolated by obtaining a mononuclear and platelet rich fraction (PB‐MPRF and BM‐MPRF, respectively). Starting with comparable volumes, the number of platelets increased 1.5‐fold in BM‐MPRF compared to PB‐MPRF. The number of clonogenic cells in BM‐MPRF samples was significantly higher than whole BM samples as revealed by CFU‐F assay (54.92 ± 8.55 CFU‐F/1.5 x 10⁵ nucleated cells and 32.50 ± 12.43 CFU‐F/1.5 x 10⁵ nucleated cells, respectively). Cells isolated from BM‐MPRF after in vitro expansion fulfilled the definition of MSCs by phenotypic criteria, and differentiated along osteogenic, adipogenic and chondrogenic lineages following induction. Results showed that the kit isolated MSCs and platelets from BM aspirate. Isolated MSCs were further expanded in a laboratory and BM‐MPRF was used clinically following BM withdrawal for rapid intra‐operative cell therapy for the treatment of bone defects. Copyright © 2012 John Wiley & Sons, Ltd.     

A study of Adenosine-Deaminase genetic polymorphism in rheumatoid arthritis

Recent investigations suggest that Adenosine Deaminase (ADA) could play a role in susceptibility to rheumatoid arthritis (RA). The purpose of our study is to investigate the possible role of genetic variability of ADA in the susceptibility to RA. We studied three intragenic ADA polymorphisms, ADA1, ADA2 and ADA6, in a sample of 91 subjects with RA and in 246 healthy subjects from the same Caucasian population and compared genotype and pairwise haplotype distributions between cases and controls. No statistically significant differences between RA and controls are observed for ADA genotypes. A border line difference for ADA1-ADA2 haplotype distribution is observed due to a decreased proportion of ADA1 *2/ADA2 *2 haplotype in RA compared to controls. Our data indicate a border line effect of ADA gene polymorphism on susceptibility to RA that need to be confirmed in other clinical settings.     

Differences in the Evaluation and Management of Exercise-Induced Bronchospasm between Family Physicians and Pulmonologists

Previous studies have demonstrated that specialists and generalists differ in the evaluation and management of asthma especially in terms of use of objective testing. We speculated that there also may be differences in the diagnosis and management of exercise-induced respiratory complaints. An Internet survey was sent to samples of pulmonologists and family physicians. Our data suggests that pulmonologists are much more likely to order bronchoprovocation testing than family physicians, and family physicians are more likely to start any empiric therapy than perform bronchoprovocation testing when exercise-induced bronchospasm is suspected. These differences may lead to inaccurate or missed diagnoses and unnecessary morbidity.     

Psychological stress affects response to sublingual immunotherapy in asthmatic children allergic to house dust mite

While the clinical and immunologic efficacy of sublingual immunotherapy (SLIT) in allergic diseases has been extensively demonstrated, some patients display a poor clinical response. Psychological stress has been shown to play a role in atopy and also to affect response to immunomodulating therapies such as vaccination with microbial antigens. This study addresses the possibility of response to SLIT being affected by psychological stress. Forty children with mild asthma caused by allergy to Dermatophagoides pteronyssinus and farinae were subjected to SLIT and then divided after 6 months into two groups based on the results of the stress integrated measure (SIM) test: group 1 (24 stressed patients, mean SIM value of 60.1) and group 2 (16 non-stressed patients, mean SIM value of 7.6). There was also a higher prevalence of psychosocial stressing factors (divorced/absent parents, low income households, non-working parents) among stressed patients. The symptom score, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1)) and serum eosinophie cationic protein (ECP) concentration were evaluated at both times. The serum concentration of neuroendocrine parameters [prolactin, cortisol, adrenocorticotropic hormone (ACTH)] was also measured after 6 months of therapy. While all the clinical parameters and ECP concentration improved after SLIT, symptom score, PEF and ECP showed a significantly greater improvement in non-stressed patients. The concentration of neuroendocrine parameters was significantly increased in stressed patients. Our findings show that psychological stress can affect response to SLIT also in allergic subjects and are consistent with data recently reported showing a correlation between stress and poor response to antimicrobial vaccines. Our data also suggest that stress evaluation may become a useful prognostic factor in immunotherapy.