Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study.

AIMS: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months. METHODS: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years. RESULTS: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and,  of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes. CONCLUSIONS: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged.

Predictors of cord blood unit cell content in a volume unrestricted large series collections: a chance for a fast and cheap multiparameter selection model.

BACKGROUND: Cord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content. METHODS: Maternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content. RESULTS: Our univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie's gender and birth weight have a positive correlation with CB TNC content. The babie's birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie's, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 108 (group A) have a significant higher CD34+ content than group B (female babie's, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 106, while no CBUs with high concentration of CD34+ were detect in group B. CONCLUSION: This study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries.

Total nucleated cells as a sole predictor of distinct targets of hematopoietic potential (CD34+ cells) in cord blood units: the results of a large series analysis in autologous cord blood units.

BACKGROUND: Rapid identification of eligible cord blood units (CBUs) for banking is an important issue in hematopoietic stem cell procurement. Distinct contents of CD34+ cells in CBU can contribute to identify grafts that may be banked also for unrelated transplants or limited to family-directed or autologous use. STUDY DESIGN AND METHODS: Considering thresholds of CD34+ cell content of 3 × 10(6) , 2 × 10(6) , and 1 × 10(6) CD34+ cells, we analyzed a consecutive series of 1309 CBUs. CBUs were collected for autologous banking without any volume-based preselection criteria. Predictors of distinct content of CD34+ cells have been assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: Median total nucleated cell (TNC) and CD34+ cell counts of the series were 6.97 × 10(8) (range, 0.36 × 10(8) -34.9 × 10(8) ) and 1.47 × 10(6) (0-20.56 × 10(6) ). Volumes ranged from 21 to 163 mL, with a median of 73.8 mL. For the CD34+ target of 1 × 10(6) , the best predictor was TNC count with a threshold of 6.63 × 10(8) ; volume results were less predictive with a value of 68.1 mL. For CD34+ targets of 2 × 10(6) and 3 × 10(6) , ROC curves confirmed a stronger predictive power of TNC, above the collected volume, with thresholds of 7.55 × 10(8) and 8.98 × 10(8) . ROC analysis by combining all predictors (TNC, volume, TNC(2) , volume(2) , age of mothers, types of delivery, birthweight) gave worse results than TNC count alone. CONCLUSIONS: This analysis, carried out on a large, unrestricted CBU series, shows that TNC alone is the best predictor of distinct targets of hematopoietic potential with the chance to predict CBU potentially useful for unrelated recipients or limited for family-directed or autologous use.

High survival of frozen cells irradiated with gamma radiation.

Cell storage in liquid nitrogen (LN) offers the most secure method of cell preservation even if cryopreserved cells are exposed to natural background of ionising radiation (IR). A lot of experiments have demonstrated that IR can induce damages in living cells, but only a little information regarding the response of cryopreserved cells is available. To investigate the effect of IR on frozen and unfrozen cells, peripheral blood mononuclear cells were directly irradiated at room temperature, then immediately frozen, or frozen and then irradiated in LN with different doses of gamma rays. After thawing, cells were incubated and death fraction was evaluated at different time points. Interestingly, the percentages of dead cells induced by IR gradually increased with both dose radiation and incubation time and were significantly lower for cells irradiated at -196°C than those irradiated at room temperature.

[Appropriateness of prescription of exercise stress test, echocardiography, Holter monitoring and vascular echography]. / L'appropriatezza dei test cardiologici non invasivi. studio osservazionale sull'appropriatezza della prescrizione del test da sforzo, dell'ecocardiogramma, dell'ECG dinamico e dell'ecografia vascolare.

BACKGROUND: The aim of this study was to evaluate the appropriateness of prescription of non-invasive cardiological tests (exercise stress test, echocardiography, Holter monitoring and vascular echography), consecutively performed in our outpatient laboratory during 4 weeks. METHODS: We collected the following data: the appropriateness of prescription (according to the Italian Federation of Cardiology guidelines); test indications; the prescribing physician (cardiologist/non-cardiologist); type of prescription (elective/urgent); clinical utility (useful/useless) and result (normal/abnormal) of each test. RESULTS: We evaluated 960 prescriptions (320 exercise tests; 282 echocardiograms; 158 Holter tests; 200 vascular echographies). Test indications were appropriate (class I) in 37%, doubtfully appropriate (class II) in 39% and inappropriate (class III) in 24% of the cases. The appropriateness was slightly better for vascular echography and echocardiography (class I: 44% and 43%, respectively), markedly worse for exercise test (class I: 27%). The tests were considered useful in 46% and abnormal in 39% of the cases. Cardiologist-prescribed exams resulted more often appropriate (class I: 53 vs 30%; class II: 41 vs 38%; class III: 6 vs. 32%; p = 0.0001), more often useful (74 vs. 34%; p = 0.0001) and more frequently abnormal (43 vs. 37%; p = 0.05), when compared to non-cardiologist-prescribed exams. No differences in appropriateness, utility and test result have been detected between elective and urgent exams. Exercise test, echocardiogram and Holter monitoring resulted more often appropriate and useful when prescribed by cardiologists. CONCLUSIONS: This study confirms that only one third of prescriptions for non-invasive cardiological tests are appropriate. Cardiologist-prescribed exams are more often appropriate, useful and abnormal.