Results of successive EORTC-CLG 58 881 and 58 951 trials in paediatric T-cell acute lymphoblastic leukaemia (ALL)

Outcomes in childhood T-cell acute lymphoblastic leukaemia (T-ALL) are steadily improving due to intensive therapy. Between 1989 and 2008, 599 children with newly diagnosed T-ALL were enrolled in two successive European Organization for Research and Treatment of Cancer - Children's Leukaemia Group trials (58881 and 58951), both based on the Berlin-Frankfurt-Munster protocol and without cranial irradiation. In the latter trial induction chemotherapy was intensified. The most important randomizations were Medac Escherichia coli asparaginase versus Erwinia asparaginase in trial 58881, and dexamethasone (6 mg/m²/day) versus prednisolone (60 mg/m²/day) and prolonged versus conventional asparaginase duration in trial 58951. 8-year event-free survival (EFS) increased from 65·1% to 74·0% in trial 58951. Improvement was most profound for patients with white blood cell (WBC) counts <100 × 10⁹/l and “good responders” to prephase. Medac E. coli asparaginase was associated with longer EFS [hazard ratio (HR) 0·54, P = 0·0015] and overall survival (HR 0·51, P = 0·0018). Induction therapy with dexamethasone did not improve EFS compared to prednisolone. Remarkably, intensification of central nervous system (CNS)-directed therapy in trial 58951 resulted in fewer bone marrow relapses, while the incidence of CNS relapses remained low. In summary, we showed that adequate asparaginase therapy, intensified induction treatment and intensification of CNS-directed chemotherapy can result in an improvement of outcome in T-ALL patients with good prephase response and initial WBC counts <100 × 10⁹/l, representing approximately 50% of T-ALL patients.     

Fibrinogen and other coronary risk factors

The association between plasma fibrinogen concentration and other coronary risk factors diverged in previous studies, and the impact from complex lipoprotein patterns has not been studied. Our research involved 24 healthy subjects without coronary heart disease (control) and 22 patients who had survived having acute myocardial infarction before the age of 41 years (cases), overall 40 men and 6 women with age range of 34 to 54 years. In multiple linear regression analyses concerning control subjects, family disposition, social class, a score based on serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations, and fasting capillary blood glucose concentration were significantly associated with plasma fibrinogen concentration (P < .00005, R2 = 0.81). For case subjects, the ratio between serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations was significantly associated with plasma fibrinogen concentration (P = .0018, R2 = 0.39). Thus, for healthy subjects, 4 coronary risk factors explained three quarters of the variation of plasma fibrinogen concentration, and for patients with a previous acute myocardial infarction, another coronary risk factor explained one third of the variation. In conclusion, the pattern of coronary risk factors associated with plasma fibrinogen concentration differed between those without coronary heart disease and those with a previous acute myocardial infarction.     

Prognostic value of cytologic parameters in acute myelogenous leukemia

The prognostic value of some current cytologic characteristics was assessed in 174 adult patients with acute myelogenous leukemia (AML) treated according to the AML-5 protocol of the EORTC Leukemia and Hematosarcomas Group. A significantly higher rate of complete remission (CR) was observed in patients with low bone-marrow (BM) cellularity, with BM blasts less than 80%, and with Auer rod positive cells more than 2.5% of the total blast cell population. A leukocyte count of less than 50 X 10(9)/1 in the peripheral blood was also associated with a higher CR rate. No significant difference was found between the various French-American-British (FAB) subtypes, in spite of a trend towards a lower CR rate in patients with an M1, myeloblastic, poorly differentiated, subtype. The leukocyte count and the percentage of Auer rod positive cells were the only significant parameters for duration of survival from the beginning of maintenance treatment. However these features had no prognostic value for the duration of remission. It seems therefore that patients with a higher percentage of Auer-rod-positive cells and lower peripheral leukocyte counts can enter remission more easily, and can also more readily achieve subsequent remissions following relapse. The prognostic value of these routine cytologic features is probably related to their relationship with proliferative activity and tumor burden: the percentage of Auer-rod-positive cells correlates inversely with the leukocyte count, whereas leukocyte count, BM cellularity, and percentage of BM blasts are linked together.     

A comparison of the effect of diethylstilbestrol with low dose estramustine phosphate in the treatment of advanced prostatic cancer: final analysis of a phase III trial of the European Organization for Research on Treatment of Cancer

In a randomized phase III trial performed by the Urological Group of the European Organization for Research on Treatment of Cancer low dose estramustine phosphate (280 mg. twice daily for 8 weeks and 140 mg. twice daily thereafter) was compared to diethylstilbestrol (1 mg. 3 times daily) in patients with stages T3 to T4, M0 or M1 prostatic cancer. Of 248 patients entered 227 were evaluable for analysis: 115 received estramustine phosphate and 112 received diethylstilbestrol. The best response of the local tumor as assessed by palpation was seen in patients receiving diethylstilbestrol. There was no significant difference between treatments for response rate of metastases, interval to local progression, distant progression, over-all survival and death of carcinoma of the prostate. Duration of survival was correlated with the assessment of local response as determined by palpation. The response of distant lesions also was correlated closely with survival. Diethylstilbestrol (1 mg. 3 times daily) was associated with a significantly worse degree of cardiovascular toxicity than estramustine phosphate. This finding was especially obvious in patients who had no history of cardiovascular disease. Gastrointestinal toxicity occurred in 25 patients treated with estramustine phosphate, including 6 in whom cessation of treatment was necessary. Further studies are required to determine the optimum dose of diethylstilbestrol and estramustine phosphate, and to establish the best form of hormonal treatment for prostatic carcinoma.     

Predictors of successful salpingo-oophorectomy at the time of vaginal hysterectomy

Study ObjectiveTo determine prognostic factors related to successful salpingo-oophorectomy in menopausal women at the time of vaginal hysterectomy.DesignRetrospective cohort study (Canadian Task Force Classification II-2).SettingTertiary care center.PatientsA total of 309 postmenopausal ≥60 years old with pelvic floor disorders.InterventionsVaginal hysterectomy with attempted prophylactic salpingo-oophorectomy.MeasurementsFactors associated with ability to achieve vaginal salpingo-oophorectomy.Main Results203 (65.7%) achieved successful removal of 1 or both ovaries, and 106 (34.3%) were not amenable to removal. Younger age and shorter cervical length were predictors of salpingo-oophorectomy. Cervical elongation of ≥7 cm, exteriorized cervical/uterine prolapse, and anterior vaginal wall prolapse beyond the hymen were associated with lower likelihood of achieving salpingo-oophorectomy.ConclusionsPatient age and cervical length are independent factors that influence the success of accomplishing salpingo-oophorectomy at the time of vaginal hysterectomy.     

Is trisomy 11 another nonrandom chromosomal anomaly in acute nonlymphocytic leukemia and myelodysplastic syndromes?

Four cases with trisomy 11 as the sole chromosomal anomaly are reported, three with de novo acute nonlymphocytic leukemia (ANLL) and one with a myelodysplastic syndrome (MDS) after treatment for multiple myeloma. In reviewing the literature, we found 19 additional cases with trisomy 11 as the sole cytogenetic defect. All patients except one were reported to have ANLL or MDS. Thus, it seems that trisomy 11 is another rare but nonrandom chromosomal anomaly in ANLL and MDS. So far, no apparently characteristic clinical or cytologic signs have been found in these cases.     

Structural,Mechanical, and Decorative Properties of Sputtered TiN and Ti (N,C) Films for Orthodontic Applications; an In Vitro Study

In this paper, we explore and modify the structural, mechanical, and decorative properties of films composed by TiN and Ti (N, C) with a wide range of N₂ gas flow during the deposition in order to be used on orthodontic systems. The films were grown using reactive DC magnetron sputtering from a pure Ti target and customized with C pellets onto Si and stainless steel 316L substrates. The structural properties were studied using X-ray diffraction and scanning electron microscopy, while the mechanical ones were obtained through hardness, elastic modulus, and friction coefficient. Moreover, the wear rate has been measured under an artificial saliva medium to simulate the oral cavity. The color of the films deposited onto stainless steel 316 L substrate was characterized through CIELab color code. Our findings show that the addition of N₂ and C in the Ti matrix improves the mechanical properties of the films. With the increase in the amount of N₂ and C, the hardness reaches a value of 739 HV, higher than the one reported in the literature (600 HV), a low value of the coefficient of elasticity (8.0 GPa), and also a low friction coefficient (0.30). Moreover, with the addition of N₂ and C in the Ti films, the color of the films changes from metallic aspect until “with” gold, which means that our coatings exhibit versatile mechanical and color characteristics to be used in orthodontic wires applications.     

Characterization of metronidazole-phosphate, a water-soluble metronidazole derivative, as a radiosensitizer of hypoxic cells.

A water-soluble derivative of metronidazole (Flagyl) was synthetized with the purpose to overcome some practical difficulties in the clinical administration of the drug. The derivative, a phosphate ester of metronidazole, was characterized for different physical-chemical properties. It had a low toxicity both in vitro and in vivo. In vitro, it retained a radiosensitizing effect specific for hypoxic cells which was, however, decreased in comparison with the parent compound. The decreased sensitization was related to a decreased one-electron reduction potential and octanol/water partition coefficient. In mice, metronidazole-phosphate had a prolonged blood life in comparison to metronidazole.