Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network

Mantle-cell lymphoma (MCL) is characterized by poor prognosis with a median survival of only 3 to 4 years. To improve clinical outcome, the European MCL Network initiated a randomized trial comparing consolidation with myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) to alpha-interferon maintenance (IFN alpha) in first remission. Patients 65 years of age or younger with advanced-stage MCL were assigned to ASCT or IFN alpha after achievement of complete or partial remission by a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like induction therapy. According to the International Prognostic Index (IPI), 43% of patients had a low-risk, 41% a low-intermediate, 11% a high-intermediate, and 6% a high-risk profile. Sixty-two of 122 patients proceeded to ASCT and 60 received IFN alpha. Patients in the ASCT arm experienced a significantly longer progression-free survival (PFS) with a median of 39 months compared with 17 months for patients in the IFN alpha arm (P = .0108). The 3-year overall survival (OS) was 83% after ASCT versus 77% in the IFN group (P = .18). Early consolidation by myeloablative radiochemotherapy followed by ASCT is feasible and results in a significant prolongation of PFS in advanced-stage MCL. Longer follow-up is needed to determine the effect on OS.     

Innovative Verfahren der Vorhofflimmertherapie

Pulmonary vein isolation (PVI) is the established cornerstone in most catheter-based ablation treatment strategies for atrial fibrillation (AF); however, it is still a challenge to create contiguous, transmural and permanent ablation lesions using radiofrequency current in combination with three-dimensional mapping systems. To overcome these limitations, innovative spiral mapping and ablation catheters as well as balloon-based ablation catheters incorporating alternative energy sources, such as cryoenergy and laser were developed and evaluated and have proved their potential for safe and clinically effective PVI. In addition, novel ablation strategies, such as identification and ablation of AF-inducing foci and/or AF-perpetuating rotors using either endocardial or epicardial mapping systems were introduced and are currently under clinical evaluation. The identification and modulation of atrial ganglionic plexi (GP) and, therefore, of the autonomous nervous system is another additive ablation approach which requires further clinical evaluation.     

Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL

The combination of cyclophosphamide, doxorubicin, vincristine, and prednisone, given every 3 weeks (CHOP-21) is standard chemotherapy for aggressive lymphomas. To determine whether CHOP given every 2 weeks (CHOP-14) or the addition of etoposide (CHOEP-21, CHOEP-14) can improve results in patients ages 18 to 60 years with good prognosis (normal lactic dehydrogenase [LDH] level), 710 patients were randomized to 6 cycles of CHOP-21, CHOP-14, CHOEP-21 (CHOP plus etoposide 100 mg/m2 days 1-3), or CHOEP-14 in a 2 x 2 factorial study design. Patients in the biweekly regimens received granulocyte colony-stimulating factor (G-CSF) starting from day 4. Patients received radiotherapy (36 Gy) to sites of initial bulky disease and extranodal disease. CHOEP achieved better complete remission (87.6% versus 79.4%; P =.003) and 5-year event-free survival rates (69.2% versus 57.6%; P =.004, primary end point) than CHOP, whereas interval reduction improved overall survival (P =.05; P =.044 in the multivariate analysis). Although the CHOEP regimens induced more myelosuppression, all regimens were well tolerated. CHOEP should be the preferred chemotherapy regimen for young patients with good-prognosis (normal LDH level) aggressive lymphoma.     

The problem of hypertension and ovulation inhibitors]

It is reported on a 46-year-old woman who died of a haemorrhage of the cerebral matter in renally fixed hypertension and severe arteriosclerosis of the arteries of the basis of the brain. The possible connection between hypertension, arteriolosclerosis of the kidneys and arterioclerosis of the arteries of the brain basis and an intake of ovulation inhibitors lasting 10 years is critically discussed.     

Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group

Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma (FL) when it is added to chemotherapy. In the current study, 428 patients with untreated, advanced-stage FL were randomly assigned for therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone (n = 205) or CHOP combined with rituximab (R-CHOP) (n = 223). R-CHOP reduced the relative risk for treatment failure by 60% and significantly prolonged the time to treatment failure (P < .001). In addition, a significantly higher overall response rate (96% vs 90%; P = .011) and a prolonged duration of remission (P = .001) were achieved. In spite of a relatively short observation time, these beneficial effects even translated to superior overall survival (P = .016), with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years. The predominant treatment-related adverse effect was myelosuppression. Severe granulocytopenia was more frequently observed after R-CHOP (63% vs 53%; P = .01). However, severe infections were rare and of similar frequency after R-CHOP and CHOP (5% and 7%). Hence, adding rituximab to CHOP significantly improves the outcome for patients with previously untreated advanced-stage FL and does not induce major adverse effects.     

APOBEC3 enzymes restrict marginal zone B cells

In general, a long‐lasting immune response to viruses is achieved when they are infectious and replication competent. In the mouse, the neutralizing antibody response to Friend murine leukemia virus is contributed by an allelic form of the enzyme Apobec3 (abbreviated A3). This is counterintuitive because A3 directly controls viremia before the onset of adaptive antiviral immune responses. It suggests that A3 also affects the antibody response directly. Here, we studied the relative size of cell populations of the adaptive immune system as a function of A3 activity. We created a transgenic mouse that expresses all seven human A3 enzymes and compared it to WT and mouse A3‐deficient mice. A3 enzymes decreased the number of marginal zone B cells, but not the number of follicular B or T cells. When mouse A3 was knocked out, the retroelement hitchhiker‐1 and sialyl transferases encoded by genes close to it were overexpressed three and two orders of magnitude, respectively. We suggest that A3 shifts the balance, from the fast antibody response mediated by marginal zone B cells with little affinity maturation, to a more sustained germinal center B‐cell response, which drives affinity maturation and, thereby, a better neutralizing response.     

Comparative study of application accuracy of two frameless neuronavigation systems: experimental error assessment quantifying registration methods and clinically influencing factors

This study aimed at comparing the accuracy of two commercial neuronavigation systems. Error assessment and quantification of clinical factors and surface registration, often resulting in decreased accuracy, were intended. Active (Stryker Navigation) and passive (VectorVision Sky, BrainLAB) neuronavigation systems were tested with an anthropomorphic phantom with a deformable layer, simulating skin and soft tissue. True coordinates measured by computer numerical control were compared with coordinates on image data and during navigation, to calculate software and system accuracy respectively. Comparison of image and navigation coordinates was used to evaluate navigation accuracy. Both systems achieved an overall accuracy of <1.5 mm. Stryker achieved better software accuracy, whereas BrainLAB better system and navigation accuracy. Factors with conspicuous influence (P < 0.01) were imaging, instrument replacement, sterile cover drape and geometry of instruments. Precision data indicated by the systems did not reflect measured accuracy in general. Surface matching resulted in no improvement of accuracy, confirming former studies. Laser registration showed no differences compared to conventional pointers. Differences between the two systems were limited. Surface registration may improve inaccurate point-based registrations but does not in general affect overall accuracy. Accuracy feedback by the systems does not always match with true target accuracy and requires critical evaluation from the surgeon.