Elter T.,University of Cologne |
Gercheva-Kyuchukova L.,Varna Clinic of Haematology |
Pylylpenko H.,Cherkasy Oncology Center |
Robak T.,Medical University of Lodz |
And 8 more authors.
The Lancet Oncology | Year: 2011
Background: Chronic lymphocytic leukaemia (CLL) is an incurable and chronic disorder, with worsening prognosis for patients as their disease progresses. We compared the efficacy and safety of the combination of fludarabine and alemtuzumab with fludarabine monotherapy in previously treated patients with relapsed or refractory CLL. Methods: Patients (aged ≥18 years) with CLL Binet stage A, B, or C or Rai stages I-IV were randomly assigned in a 1:1 ratio according to a computer-generated allocation schedule to open-label combination treatment (fludarabine 30 mg/m 2 per day and alemtuzumab 30 mg per day on days 1-3) or monotherapy (fludarabine 25 mg/m 2 on days 1-5) by use of an interactive voice response system. Both regimens were given intravenously for a maximum of six 28-day cycles. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00086580. Findings: Fludarabine plus alemtuzumab (n=168) resulted in better PFS than did fludarabine monotherapy (n=167; median 23·7 months [95% CI 19·2-28·4] vs 16·5 months [12·5-21·2]; hazard ratio 0·61 [95% CI 0·47-0·80]; p=0·0003) and overall survival (median not reached vs 52·9 months [40·9-not reached]; 0·65 [0·45-0·94]; p=0·021) compared with fludarabine alone. All-cause adverse events occurred in 161 (98%) of 164 patients in the combination treatment group and 149 (90%) of 165 in the fludarabine alone group. Patients in the fludarabine plus alemtuzumab group had more cytomegalovirus events (23 [14%] vs one [<1%]) and grade 1 or 2 potentially alemtuzumab infusion-related adverse reactions (102 [62%] vs 22 [13%]). Grade 3 or 4 toxicities in the combination treatment and monotherapy groups were leucopenia (121 [74%] of 164 vs 55 [34%] of 164), lymphopenia (149 [94%] of 158 vs 53 [33%] of 161), neutropenia (93 [59%] of 157 vs 110 [68%] of 161), thrombocytopenia (18 [11%] of 164 vs 27 [17%] of 163), and anaemia (14 [9%] of 163 vs 28 [17%] of 164). The incidence of serious adverse events was higher in the combination treatment group (54 [33%] of 164 vs 41 [25%] of 165); deaths due to adverse events were similar between the two groups (ten [6%] vs 12 [7%]). Interpretation: The combination of fludarabine and alemtuzumab is another treatment option for patients with previously treated CLL. Funding: Genzyme. © 2011 Elsevier Ltd. Source
Naessen T.,Uppsala University |
Kushnir M.M.,Arup |
Kushnir M.M.,Uppsala University |
Chaika A.,Donetsk State Medical University |
And 7 more authors.
Fertility and Sterility | Year: 2010
Objective: To compare steroid concentrations and steroid product-to-precursor ratios in ovarian follicular fluid (FF) from women with polycystic ovary syndrome (PCOS) and from regularly menstruating women in their early follicular phase, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polycystic ovary syndrome involves abnormal regulation of the steroidogenic enzymes, leading to arrest of follicle development. Design: Case-control study. Setting: University hospital clinic. Patient(s): Follicular fluid from size-matched ovarian follicles (5-8 mm) in 27 nonstimulated women with PCOS and in 21 women without PCOS was sampled. Thirteen steroids were quantitated from 40 μL of FF, using LC-MS/MS. Intervention(s): None. Main Outcome Measure(s): Concentrations of steroids in the FF and product-to-precursor ratios (enzyme activity) were compared between the groups. Result(s): In women with PCOS, ovarian FF contained higher concentrations of individual and total androgens, lower individual and total estrogens (E), and a lower total E-to-androgen ratio, compared with regularly menstruating women. The product-to-precursor concentration ratios indicated higher CYP17-linked and lower CYP19-linked (aromatase) enzyme activity. Receiver operating characteristic plots indicated the early CYP17 step (17-OH5P/5P) being highly important for the prevalence of PCOS (c = 0.95). Conclusion(s): The women with PCOS had higher ovarian CYP17-linked and lower CYP19-linked (aromatase) enzyme activity, confirming previous data. Multiple steroid assessments from minute volumes including FF from nonstimulated ovaries, using LC-MS/MS, might be useful in research, clinical endocrinology, and in IVF. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc. Source
Hedt B.L.,Harvard University |
Van Leth F.,Amsterdam Institute for Global Health and Development |
Zignol M.,World Health Organization |
Cobelens F.,Amsterdam Institute for Global Health and Development |
And 6 more authors.
Epidemiology | Year: 2012
Background: Current methodology for multidrug-resistant tuberculosis (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. Methods: We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored 3 classification systems - two-way static, three-way static, and three-way truncated sequential sampling - at 2 sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. Results: The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. Conclusions: Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desired. Copyright © 2012 by Lippincott Williams & Wilkins. Source
Gerasimov I.G.,Donetsk State Medical University
Cell and Tissue Biology | Year: 2013
Kinetics of morphometrical parameters (perimeter, square, compactness) of human blood neutrophils attached to object glass is described by equations similar to the kinetical equations of irreversible reactions of the first reactions. The calculated values of morphometrical parameters of neutrophils in suspension and those attached to glass agree with the literature data. It has been found that compactness of neutrophils in the process of attachment is not changed. The time of completion of the process of attachment amounts approximately to 3 h. © 2013 Pleiades Publishing, Ltd. Source
An open-label, multicenter, randomized phase Ib/II study of eribulin mesylate administered in combination with pemetrexed versus pemetrexed alone as second-line therapy in patients with advanced nonsquamous non-small-cell lung cancer
Waller C.F.,University Hospital Freiburg |
Vynnychenko I.,Sumy State University |
Bondarenko I.,Donetsk State Medical University |
Shparyk Y.,Lviv State Oncology Regional Treatment and Diagnostic Center |
And 6 more authors.
Clinical Lung Cancer | Year: 2015
Introduction New treatment options are needed for second-line therapy in patients with NSCLC. Patients and Methods This was a phase Ib/II study in patients with nonsquamous NSCLC in whom 1 previous platinum-based chemotherapy regimen had failed. Fifteen patients were enrolled in a dose escalation of eribulin mesylate in combination with pemetrexed (E+P). In phase II (n = 80), E+P at the maximum tolerated dose was compared with P. Results In phase Ib, the maximum tolerated dose of E+P was defined as eribulin 0.9 mg/m2 with pemetrexed (500 mg/m2) each on day 1 of a 21-day cycle. In phase II, adverse events were comparable between groups. PFS and OS were similar between treatment groups. Median PFS was 21.4 weeks for E+P (n = 26; 95% confidence interval [CI], 12.7-39.6) and 23.4 weeks for P (n = 29; 95% CI, 17.1-29.9), with a hazard ratio of 1.0 (95% CI, 0.6-1.7). Conclusion During phase Ib, E+P was tolerated only at a markedly lower dosing intensity relative to the eribulin monotherapy regimen approved for breast cancer and used in phase II studies of NSCLC. At the selected phase II dosing regimen, E+P was generally safe and well tolerated but provided no therapeutic advantage for the second-line treatment of locally advanced or metastatic nonsquamous NSCLC. © 2015 Elsevier Inc. Source