Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up.

BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.

A 4-weekly course of rituximab is safe and improves tumor control for patients with minimal residual disease persisting 3 months after autologous hematopoietic stem-cell transplantation: results of a prospective multicenter phase II study in patients with follicular lymphoma.

BACKGROUND: This study explored the efficacy and safety of rituximab as treatment of clinical or molecular residual disease after autologous stem-cell transplantation (ASCT) in follicular lymphoma (FL). PATIENTS AND METHODS: Forty patients with CD20+ FL and clinically (group A, n = 14) or clono-specific PCR-detectable (group B, n = 25) residual disease persisting 3 months after ASCT received rituximab 375 mg/m² once weekly for 4 weeks. RESULTS: Response rate at day 50 was 36% [90% confidence interval (CI) 15-61] in group A (World Health Organization criteria) and 52% (90% CI 34-70) in group B (conversion PCR-undetectable status to undetectable status). The best response rate was 71% [nine complete responses (CRs) and one partial response] in group A and 76% in group B. At 36 months, all 10 responses persisted in group A, whereas 46% of patients in group B still had PCR-undetectable disease. Furthermore, 68% of patients in group B were still in clinical CR. Rituximab after ASCT was safe with few grade 3-4 toxic effects (15% patients), mainly acute reactions and infections. CONCLUSION: Rituximab induced a high rate of durable CRs in patients with clinically detectable disease, as well as durable eradication of PCR-detectable disease in patients with FL after ASCT. Continued molecular responses assessed with a highly sensitive and clono-specific PCR technique were correlated with an excellent disease control.

Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy.

BACKGROUND: We investigated whether circulating tumor cells (CTCs) and circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy combined with bevacizumab in metastatic breast cancer patients. PATIENTS AND METHODS: In a French substudy of the MO19391 trial, CTC and CEC counts (CellSearch system) at baseline and changes after two cycles of treatment were correlated with time to progression (TtP). RESULTS: CTC and CEC levels were not correlated in the 67 patients included. At baseline, CTC positivity was a significant prognostic marker for TtP at a threshold of 3 CTC/7.5 ml (P < 0.05) but not at 5 CTC/7.5 ml (P = 0.09). Baseline CEC levels (median 17 CEC/4 ml, range 1-769) were associated with age > or =45 years (P = 0.01), elevated lactate dehydrogenase (P < 0.01) and not with TtP at any threshold. Changes of CTC count during treatment were not a surrogate of TtP, with any of the model tested (threshold based or relative decrease in percent). However, increase in CEC count was associated with improved TtP, at the threshold of 20 CEC/4 ml (P < 0.01). CONCLUSION: Bevacizumab combined with first-line chemotherapy may modify the predictive value of CTC during treatment possibly due to impaired tumor cells intravasation through vessels endothelium. Variations in CEC levels appear to be a promising early surrogate marker of TtP under antiangiogenic treatment.

Incidence, risk factors and clinical consequences of neutropenia following kidney transplantation: a retrospective study.

Neutropenic episodes in kidney transplant patients are poorly characterized. In this retrospective study, neutropenia was experienced by 112/395 patients (28%) during the first year posttransplant. The only factor found to be significantly associated with the occurrence of neutropenia was combined tacrolimus-mycophenolate therapy (p < 0.001). Neutropenic patients experienced more bacterial infections (43% vs. 32%, p = 0.04). Grade of neutropenia correlated with the global risk of infection. Discontinuation of mycophenolic acid (MPA) due to neutropenia was associated with an increased incidence of acute rejection (odds ratios per day 1.11, 95% confidence intervals 1.02-1.22) but not with reduced renal function at 1 year. The time from onset of neutropenia to MPA discontinuation correlated with the duration of neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration was safe and effective in severely neutropenic kidney graft recipients, with absolute neutrophil count >1000/microL achieved in a mean of 1.5+/-0.5 days. Neutropenia is an important and frequent laboratory finding that may exert a significant influence on outcomes in kidney transplantation. As well as leading to an increased incidence of infection, it is associated with a higher rate of allograft rejection if MPA is discontinued for >6 days (p = 0.02). G-CSF accelerates recovery of neutropenia and may be a good therapeutic alternative for severely neutropenic patients.

[Treating heart failure with carvedilol in private practice (initiating treatment and follow-up at one year. The KEOPS study]. / Traitement par carvedilol dans l'insuffisance cardiaque en pratique libérale (initiation du traitement et suivi à un an). Etude KEOPS.

AIMS: This study aimed at describing usual conditions of carvedilol use in heart failure (HF) patients. METHODS: KEOPS was a one-year, multi-centre, prospective pharmaco-epidemiological study in carvedilol treated HF patients recruited by private cardiologists. RESULTS: Two thousand nine patients (mean age: 68) with heart failure were included by 401 cardiologists. 64% of patients were in class II of NYHA and 27% in class III, 87% of patients presented stable heart failure for at least four weeks. Contraindication to beta blocking was observed in 24% of patients, mean left ventricular fraction of ejection was 39% and only 39% of patients had mean left ventricular fraction of ejection<35%. Co-medications included a diuretic agent, ACE inhibitor or ARB in 68% of cases. Eighty three percent of patients had a titration of carvedilol (median duration=1 20 days). Thirty percent reached the recommended maximal dose. The dose of carvedilol at the titration's visit for all the patients (patient in stop included) was on average 30.5 +/- 22.1 mg/day with a median on 25 [confidence interval: 23-27] During the year of follow-up, 10% of patients have stopped the treatment (3% of patients having reached the maximum recommended dose of carvedilol versus 13% for the others), for cardiovascular reasons in 50% of patients (aggravation of heart failure: 28%, symptomatic arterial hypotension: 9%, symptomatic bradycardia: 5%). Finally, symptomatology of patients has improved during the study (59% of patients in class mild to severe at inclusion, versus 36% at the end of the observation), especially for the 30% of patients followed at one year and having reached the maximum recommended dose of carvedilol. Only in univariate analysis, patients with an inclusion high weight (>85 kg) were likely less to reach recommended maximal dose (37.2 versus 8.7%, p-value<0.0001), the patients with systolic heart failure had more chance than the patients with diastolic heart failure to reach the recommended maximal dose (31 versus 17.4%, p-value=0.006), in the same way, the lack of auricular supported more the reach of recommended maximal dose (31.2 versus 24.1%, p-value=0.018) CONCLUSION: KEOPS study suggests an improvement of usual conditions of carvedilol compared to the last investigation but the persistence of prescription outside medical authorization and less dosage of this product compared with clinical studies.

Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical markers of bone turnover in menopausal women after a 12-week treatment period.

OBJECTIVE: To compare the effects of a 12-week treatment with 17ss-estradiol given alone and in sequential combination with 3.75 mg of nomegestrol acetate (Naemis), or a placebo on biochemical markers of bone turnover in menopausal women. PATIENTS AND METHODS: A double-blind, randomized, placebo and estradiol-controlled multicenter study was conducted. A total of 176 patients who had been menopausal for 1-10 years, hysterectomized or not, having no contraindications to hormone replacement therapy, without any risks factors for osteoporosis, received one of these treatments during 12 weeks: placebo, 1.5 mg estradiol (E(2)) or 1.5 mg E(2)/3.75 mg nomegestrol acetate (E(2)/NOMAC). The primary efficacy variables were the change in bone markers (total alkaline phosphatase, bone alkaline phosphatase and osteocalcin; urinary type-I collagen peptides). RESULTS: The four biochemical markers decreased only in the E(2)/NOMAC group. Bone alkaline phosphatase, osteocalcin and urinary type-I collagen peptides decreased in the E(2) group. For both active treatment groups compared to the placebo group, the changes were statistically significant after a 12-week treatment. There were no statistically significant differences between the E(2) and the E(2)/NOMAC groups except for total serum alkaline phosphatase, whose mean value decreased in the E(2)/NOMAC group but increased slightly in the E(2) group (p < 0.001). Furthermore, after a 6-week treatment, the changes in biochemical markers of bone turnover were similar to those found after 12 weeks. Safety data were satisfactory with regard to estradiol given alone or in combination with nomegestrol acetate. CONCLUSION: These results demonstrated that 1.5 mg E(2) is effective in reducing bone turnover in postmenopausal women and proved that the combination of 1.5 mg E(2) and 3.75 mg nomegestrol acetate has no deleterious effect on bone remodelling.

Size, velocity, and concentration in suspension measurements of spherical droplets and cylindrical jets.

The principle of an optical technique for simultaneous velocity, size, and concentration in suspension measurements of spherical droplets and cylindrical jets is proposed. This technique is based on phase Doppler anemometry working in the dual burst technique configuration. The particle size and velocity are deduced from the reflected signal phase and frequency, whereas the amplitude ratio between the refracted and the reflected signals is used for measuring the concentration of small scatterers inside the particles. Numerical simulations, based on geometrical optics and a Monte Carlo model, and an experimental validation test on cylindrical jets made of various suspensions, are used to validate the principle of the proposed technique. It is believed that this new technique could be useful in investigating processes in which liquid suspensions are sprayed for surface coating, drying, or combustion applications.

Monte Carlo calculation of backscattered light intensity by suspension: comparison with experimental data.

An optical device for measuring high particle concentrations is presented. The sensor consists of two optical fibers used for the emission and reception of the light scattered by particles in suspension. To describe the light path in this medium, we developed a Monte Carlo calculation including a mean free path, a phase function for particle scattering, and an absorption rate. A similarity law links concentration variations to a homothetic space transformation. A comparison between our calculation and experimental data is given for well-stirred, dense suspensions of silica particles with different sizes. A good fit is found when the model parameters (mean free path and phase function) are chosen according to the data given by a particle sizer.