Christopher Bangard

Clinical effectiveness of posaconazole prophylaxis in patients with acute myelogenous leukaemia (AML): a 6 year experience of the Cologne AML cohort

BACKGROUND Large randomized controlled trials have shown significant decreases in morbidity and mortality in leukaemia patients with posaconazole prophylaxis. However, the value of prophylaxis has been questioned in centres with a low incidence of invasive fungal diseases (IFDs) and pre-emptive treatment strategies. METHODS We prospectively evaluated the epidemiology of IFDs in acute myelogenous leukaemia (AML) patients undergoing first remission-induction chemotherapy before and after posaconazole prophylaxis had been introduced as a standard of care. Patients admitted from January 2003 to December 2005 received topical polyenes as antifungal prophylaxis (first group), while those admitted between January 2006 and December 2008 received 200 mg of oral posaconazole three times daily (second group). Other diagnostic and therapeutic standard operating procedures remained unchanged. RESULTS A total of 82 patients in the polyene prophylaxis group and 77 in the posaconazole prophylaxis group were included in the final analysis. Baseline characteristics were well matched between groups. Patients receiving topical polyene prophylaxis were more likely to experience breakthrough IFDs (19.5% and 3.9%; P = 0.003) or breakthrough aspergillosis (13.4% and 2.6%; P = 0.018) than patients receiving systemic posaconazole prophylaxis. They also had more febrile days (mean 10.7 +/- 9.66 and 7.3 +/- 5.73; P = 0.007), longer need for inpatient treatment (mean 53.0 +/- 24.16 and 46.0 +/- 14.39; P = 0.026) and a shorter fungal-free survival (78.7 and 90.4 days; P = 0.024). No significant differences were observed for persistent fever, pneumonia, lung infiltrates indicative of invasive pulmonary aspergillosis, or attributable and overall mortality. CONCLUSIONS After introduction of posaconazole prophylaxis for patients with AML, the number of febrile days, the incidence rate of IFDs and aspergillosis and the duration of hospitalization decreased significantly.

Brentuximab vedotin for relapsed or refractory CD30 hematologic malignancies: the German Hodgkin Study Group experience

The CD30-targeting Ab-drug conjugate brentuximab vedotin (SGN-35) was recently approved for the treatment of relapsed Hodgkin lymphoma and anaplastic large-cell lymphoma by the Food and Drug Administration. In the present study, we report the experience of the German Hodgkin Study Group with brentuximab vedotin as single agent in 45 patients with refractory or relapsed CD30(+) Hodgkin lymphoma who were treated either in a named patient program (n = 34) or in the context of a safety study associated with the registration program of this drug. In these very heavily pretreated patients, an objective response rate of 60%, including 22% complete remissions, could be documented. The median duration of response was 8 months. This retrospective analysis supports the previously reported excellent therapeutic efficacy of brentuximab vedotin in heavily pretreated CD30(+) malignancies.

Posaconazole concentrations in the central nervous system

more susceptible to the killing activity of caspofungin. This study is the first comparing caspofungin killing activity against the closely related species C. parapsilosis, C. orthopsilosis and C. metapsilosis. Killing curves, regardless of the medium used, showed a decreasing order of susceptibility to caspofungin: C. metapsilosis . C. orthopsilosis . C. parapsilosis. Based on high echinocandin MICs for C. parapsilosis sensu stricto, in the case of isolates identified as C. parapsilosis sensu lato low MICs of echinocandins may be regarded as an indicator that an isolate is in fact C. orthopsilosis or C. metapsilosis; in the case of isolates with low echinocandin MICs, DNA-based identification – 3 of the isolates is desirable. Because C. orthopsilosis and C. metapsilosis seem to be relevant species among bloodstream isolates in some countries, this distinction may be particularly important in some epidemiological situations or in clinical situations when the use of echinocandins as therapy or prophylaxis is planned.

Association of genetic variants of methionine metabolism with methotrexate-induced CNS white matter changes in patients with primary CNS lymphoma

Methotrexate (MTX) is an important anticancer drug and the most efficient chemotherapy component in primary CNS lymphoma (PCNSL). A typical side effect of intravenous high-dose MTX is the occurrence of confluent CNS white matter changes (WMC). Because MTX directly interferes with methionine metabolism, we analyzed the impact of genetic variants of methionine metabolism on the occurrence of WMC as a model of MTX toxicity. In a retrospective analysis of 68 PCNSL patients treated with MTX-based polychemotherapy with (n = 42) or without (n = 26) intraventricular treatment, 10 genetic variants influencing methionine metabolism were analyzed. Pearsons chi(2) test and multinominal regression analysis were used to define the relevance of these genetic variants for the occurrence of WMC. In this patient sample, the occurrence of WMC was significantly predicted by the TT genotype of methylenetetrahydrofolate reductase c.677C>T (chi(2) = 8.67; p = 0.013; df = 2), the AA genotype of methylenetetrahydrofolate reductase c.1298A>C (chi(2) = 13.5; p = 0.001; df = 2), and the GG genotype of transcobalamin 2 c.776C>G (chi(2) = 19.73; p < 0.001), in addition to male gender (chi(2) = 11.95; p = 0.001). These data strengthen the hypothesis that MTX effects are influenced by methionine metabolism, which may offer new strategies to improve MTX-based therapies.

Feasibility of peripheral contrast-enhanced magnetic resonance angiography at 3.0 Tesla with a hybrid technique: comparison with digital subtraction angiography.

Purpose:To prospectively determine feasibility and diagnostic accuracy of 3D contrast-enhanced MR-angiography (CE-MRA) at 3.0 tesla (T) in patients with peripheral arterial occlusive disease. Digital subtraction angiography (DSA) was used as reference standard. Material and Methods:Thirty consecutive patients with suspected peripheral arterial occlusive disease were examined on a 3.0 T MR system by using the integrated whole body coil. A 4-station examination protocol in hybrid technique was chosen, containing 2 gadodiamide injections, the first one for imaging the calf and foot arteries (single-step technique) and the second injection for the visualization of the aortoiliacal and femoral arteries (bolus-chase MRA). All patients underwent DSA within the following 48 hours. The arterial tree of each leg was divided in 15 segments and 4 anatomic regions (iliacal, femoral, popliteal/proximal calf, distal calf/foot). Two radiologists analyzed the MR-images with regard to image quality, grade of stenosis, and venous overlap. DSA-images were analyzed by 2 radiologists in consensus with regard to the stenosis grade. Results:Eight hundred eighty-five and 884 of 889 arterial segments at CE-MRA were rated with excellent or good diagnostic image quality by observer 1 and observer 2, respectively. In only 3 segments image quality was affected by venous contamination. Sensitivity of CE-MRA for determination of relevant arterial stenoses (50%–99%) and occlusions—as compared with DSA—was 95.3% (both observer) and specificity was 98.5% and 97.8% for observer 1 and observer 2, respectively. Conclusion:Peripheral hybrid CE-MRA at 3.0 T is feasible and proved to be reliable at depiction of stenoses and occlusions of the whole pelvic and lower leg arterial system.

Brentuximab vedotin (SGN-35) in patients with transplant-naive relapsed/refractory Hodgkin lymphoma

Abstract Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease (n = 9), comorbidity (n = 4) and unknown reasons (n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT (n = 4) or allogeneic SCT (n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL.

Magnetic resonance imaging in an orthotopic rat model: Blockade of epidermal growth factor receptor with EMD72000 inhibits human pancreatic carcinoma growth

The purpose of our research was to investigate the antiangiogenic effect of the epidermal growth factor receptor monoclonal antibody (anti‐EGF‐R MAB) EMD72000, in an orthotopic human pancreatic carcinoma model in rats, assessed by magnetic resonance (MR) imaging using angiogenic surrogate markers in comparison with histopathologic findings. Human pancreatic adenocarcinoma cells L3.6pl were injected orthotopically in the pancreas of 12 athymic nude rats. Through a 21‐day course, groups of 6 rats were treated intraperitoneally with either EMD72000 or with saline solution for control animals. Dynamic contrast‐enhanced MR imaging was performed before and after the treatment to assess microvascular permeability, estimated by the endothelial transfer coefficient (KPS) and fractional plasma volumes (fPV) of the pancreatic tumors. EMD72000‐treated animals showed significantly less tumor volume progression (1,080 mm3 ± 1,244; p = 0.012) and significantly lower values for microvascular permeability (KPS = 4.2 ml min−1 100 ml−1 of tissue ± 2.8; p = 0.015), fractional plasma volume (fPV = 0.018 ml ml−1 of tissue ± .015; p = 0.003) and microvessel density (MVD = 13 ± 4 (0.159 mm2); p = 0.001) than saline‐treated animals (6,544 mm3 ± 5,202; 9.5 ml min−1 100 ml−1 of tissue ± 4.3, 0.056 ml ml−1 of tissue ± 0.019 and 25 ± 5 (0.159 mm2), respectively). KPS and fPV values showed moderate positive correlation with MVD (r = 0.5, p = 0.103; r = 0.6, p = 0.065, respectively). Intraperitoneal injection of EMD72000 inhibits orthotopic human pancreatic carcinoma growth in rats. Antiangiogenic effects of anti‐EGF‐R MAB EMD72000 can be quantified and monitored noninvasively by dynamic MR imaging.

Real-time MR-guided Wire Localization of Breast Lesions by Using an Open 1.0-T Imager: Initial Experience

The purpose of this study was to prospectively evaluate technique and time factors for real-time magnetic resonance (MR) imaging-guided wire localization of suspicious breast lesions by using an open 1.0-T MR imager. It was conducted with institutional review board approval; informed consent was given by patients. Needle placement was monitored in 30 women (mean age, 50.5 years; range, 28-70 years) by using a dynamic balanced gradient-echo (single-shot turbo field-echo [TFE]) sequence with a temporal resolution of 0.5 second. In all patients, the tip of the needle was clearly identified during placement. Consistent with balanced TFE (BTFE) imaging, diagnostic MR imaging after the interventional procedure confirmed that the hookwires were placed 0-6 mm (mean, 3.3 mm) from the target lesions. The total procedure time ranged from 16-36 minutes. Results show that real-time MR-guided wire localization permits correction of the needle position during placement and reduces the interventional procedure time.

Experimental bile duct protection by intraductal cooling during radiofrequency ablation.

The use of radiofrequency ablation (RFA) for liver tumours is limited by the proximity of large bile ducts to the targeted lesion. The aim of this randomized study was to evaluate intraductal cooling as a mean of protecting the bile ducts during RFA.

Hybrid contrast-enhanced MR angiography of pelvic and lower extremity vasculature at 3.0 T: Initial experience

PURPOSE The objective of this study was to describe contrast-enhanced magnetic resonance angiography (MRA) of the lower extremities at 3.0 T system for assessment of high resolution images in patients with peripheral arterial occlusive disease (PAOD). MATERIAL AND METHODS 21 Patients with suspected PAOD were examined with four-station MRA at a 3.0 T MR system. The MRA protocol consisted of a hybrid technique with two contrast media injections, the first one for visualization of the calf and foot vasculature (non-moving-table technique), the second one for imaging the aortoiliacal and femoral arteries (moving-table technique). For the femoropopliteal and calf station a randomly segmented central k-space ordering (contrast-enhanced timing-robust angiography [CENTRA]) was used. MR-images were analyzed independently by two radiologists with regard to image quality, venous overlap and grade of stenosis. In 6 patients digital subtraction angiography was performed within the following 7 days and evaluated by two radiologists in consensus with regard to the grade of stenosis. The vasculature-tree of each leg was divided in 12 segments, and 3 anatomical regions (iliacal, femoropopliteal, calf/foot). RESULTS 490 and 488 of 495 arterial segments were visualized with diagnostic image quality by observer 1 and observer 2, respectively. Image quality was excellent in 470 and 457 arterial segments, respectively. Only 4 segments were rendered as non-diagnostic due to venous overlap. Relevant arterial stenoses (50-99%) were detected in 43 and 47 segments by observer 1 and observer 2, 66 and 65 arterial segments, respectively, were interpreted as occluded. CONCLUSION The hybrid MRA protocol at 3.0 T offers high diagnostic quality for the whole peripheral arterial tree without venous contamination at high spatial resolution.