: The present study aimed to evaluate the side‐effects and efficacy of thalidomide in combination with an anthracycline‐containing chemotherapy regimen in previously untreated myeloma patients. ...Thalidomide (400 mg/d) was combined with bolus injections of vincristine and epirubicin and oral dexamethasone (VED). Chemotherapy cycles were repeated every 3 wk until no further reduction in myeloma protein was observed, whereas the treatment with thalidomide was continued until disease progression. Thirty‐one patients were enrolled, 12 patients were exclusively treated with thalidomide in combination with VED and 19 patients additionally received high‐dose melphalan, for consolidation. Adverse events and response to therapy were assessed prior to treatment with high‐dose chemotherapy. Response to thalidomide combined with VED was complete remission in six patients (19%), partial remission in 19 patients (61%), stable disease in five patients (16%), and progressive disease in one patient (3.2%). Grade 3 and 4 adverse events consisted of leukocytopenia in 10 patients (32%), and thrombocytopenia and anemia in one patient each (3.2%). Neutropenic infections grade 3 and 4 occurred in seven (23%) and three patients (9.7%), respectively, including two patients (6.5%) who died from septic shock. Deep vein thrombosis occurred in eight patients (26%), constipation in 20 patients (65%), and polyneuropathy in 20 patients (65%). The probability of event‐free survival and overall survival in the whole group of patients at 36 months were 26 and 62%, respectively. In conclusion, the combination of thalidomide with VED appears to be highly effective in previously untreated patients with multiple myeloma, but it is associated with a high rate of thrombotic events, polyneuropathy, and neutropenic infections.
The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, ...and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone ( P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.
The FRagment Separator FRS at GSI is a versatile spectrometer and separator for experiments with relativistic in-flight separated short-lived exotic beams. One branch of the FRS is connected to the ...target hall where the bio-medical cave (Cave M) is located. Recently a joint activity between the experimental groups of the FRS and the biophysics at the GSI and Department of physics at LMU was started to perform biomedical experiments relevant for hadron therapy with positron emitting carbon and oxygen beams. This paper presents the new ion-optical mode and commissioning results of the FRS-Cave M branch where positron emitting 15O-ions were provided to the medical cave for the first time. An overall conversion efficiency of 2.9±0.2×10−415O fragments per primary 16O ion accelerated in the synchrotron SIS18 was reached.
The aim of this study was to assess the side effects and the efficacy of thalidomide alone or in combination with dexamethasone in relapsed multiple myeloma (MM) and to evaluate possible predictive ...factors for response rate and survival. Twenty-nine pretreated patients were enrolled, including 13 patients with a relapse after high-dose chemotherapy. The median number of relapses was 3 (range: 1-7). Twenty-two patients received thalidomide in combination with dexamethasone and seven patients thalidomide alone. The dosage of thalidomide was 400 mg/day and the dosage of dexamethasone 20 mg/m2 daily for 4 consecutive days every 3 weeks. Cycles of dexamethasone were given until maximal decline of myeloma protein was achieved, whereas therapy with thalidomide was maintained until disease progression. Responses occurred in 62% of patients, including 5 (17%) complete remissions and 13 (45%) partial remissions. The median event-free survival (EFS) was 7.2 months and the median overall survival (OS) 26.1 months. In multivariate analysis, pretreatment serum levels of soluble interleukin-2 receptor (sIL-2R) were a significant prognostic factor for EFS, and those of beta2-microglobulin (beta2M) and sIL-2R for OS. Serum levels of sIL-2R significantly increased after 3 weeks of treatment in 89% of patients, possibly representing lymphocyte activation induced by thalidomide. Two patients died of septic complications within 3 months after starting treatment with thalidomide and dexamethasone and one patient of herpes encephalitis after 26 months of treatment with thalidomide alone. Also, one case of pneumonia and one case of deep venous thrombosis of the lower limb occurred. Other side effects were somnolence, peripheral neuropathy, and bradycardia occurring in 35, 55, 38 and 55% of patients, respectively. The combination of thalidomide and dexamethasone is an effective therapy in heavily pretreated myeloma patients with a high response rate and acceptable toxicities. A powerful predictive factor both for EFS and OS was the pretreatment serum level of sIL-2R.
Background: Caspofungin has shown efficacy in empirical antifungal therapy in neutropenic patients, refractory invasive Aspergillus infections and invasive candidiasis. Here we report the currently ...largest series of patients treated with caspofungin outside clinical trials. Methods: Centres in Germany that were known to treat patients with invasive fungal infections were asked to fill out detailed questionnaires for all patients treated with caspofungin. No effort was made to influence the decision to use caspofungin. Results: A total of 118 patients were evaluable (median age 48 years, interquartile range 38–58), out of which 41 (35%) suffered from acute leukaemia, 31 (26%) had allogeneic stem cell transplants, 16 (14%) lymphoma or myeloma, 8 (7%) autologous stem cell transplants and 22 (19%) other causes for immunosuppression. One hundred and six patients were evaluable for efficacy out of which 68 (64%) patients achieved a complete or partial remission. A total of 81 out of 115 (70%) patients were alive 30 days after the end of caspofungin therapy. Response rates were similar in proven (20/32, 63%) and probable (27/46, 59%) infections, in neutropenic patients (41/55, 75%) and in patients who were (44/70, 63%) or were not (24/36, 67%) refractory to antifungal pre-treatment. The response rate in mechanically ventilated patients was 29% (7/24). Caspofungin was well tolerated, even in 14 patients, who were concomitantly treated with ciclosporin A, no drug-related elevations of bilirubin, alanine aminotransferase or creatinine were found. Conclusions: This open case study of severely ill patients with invasive fungal infections demonstrates both excellent efficacy and very low toxicity of caspofungin.
While vaccination with antigen-pulsed dendritic cells (DCs) represents a promising therapeutic strategy in multiple myeloma (MM), clinical benefit, so far, has been limited to individual patients. To ...identify potential problems with this approach, we have analyzed the influence of treatment parameters, in particular high-dose chemotherapy (HD-CTX) and thalidomide, on in vitro DC generation and peripheral blood lymphocyte subsets in MM patients. From a total of 25 MM patients, including 14 patients on thalidomide treatment and 11 after HD-CTX, in vitro DC generation from peripheral blood monocytes under serum-free condition was investigated. In addition, peripheral blood lymphocyte subsets were assessed in 17 patients including 10 patients on thalidomide treatment and 9 patients after HD-CTX. Efficient in vitro generation of DCs (median 7.1x10(6)/100 ml peripheral blood; range 0.1-42.5x10(6)/100 ml peripheral blood) expressing DC-typical surface markers was observed in 23 MM patients (92%), although reduced expression of CD1a, CD40, CD83, and HLA-DR was observed in patients treated with thalidomide. With respect to lymphocyte subsets, MM patients showed significantly (p<0.05) reduced B and CD4+ lymphocytes in the peripheral blood. This effect was most prominent within 6 months of HD-CTX and in patients receiving thalidomide (usually in combination with CTX). CD8+ lymphocytes were significantly increased in MM patients. Thus, despite the well-known deficiencies in their immune system, adequate numbers of DCs can be generated in most myeloma patients. In patients treated with thalidomide, however, it remains to be seen whether the reduced expression of co-stimulatory molecules has functional relevance.
Trapping of particles in nonlinear resonances in the presence of space charge and synchrotron motion may be a source of beam halo generation and beam loss in high intensity synchrotrons, in ...particular for extended storage times at the injection plateau as planned for the SIS100 synchrotron of the FAIR project. Although extensive simulation studies have theoretically demonstrated this mechanism, experimental evidence was so far limited to demonstration experiments at the CERN Proton Synchrotron (PS) in 2002–2003 using an octupolar resonance. Here we describe new experiments at the SIS18 synchrotron at GSI, where the resonance is driven by a sextupolar field error and horizontal static tune scans are taken across the resonance stop band. The new data significantly extend the previous observations by a complete set of measurements comparing beams with and without rf, both at low and high intensity. The correlation between transverse beam loss and simultaneous bunch length shortening provides strong evidence that the measured emittance and the loss in intensity are indeed caused by periodic resonance crossing, leading to the main effect of scattering but also to a lesser extent to the trapping of particles due to the combined effect of the nonlinear resonance and the space charge.
Hemolytic uremic syndrome (HUS) has been described following the administration of multiple antineoplastic agents, most notably mitomycin C. More recently, several cases of gemcitabine-induced HUS ...have been observed with the overall incidence of gemcitabine-induced HUS estimated at 0.015-0.25%. We here report on four patients who developed HUS following gemcitabine therapy at our institution within the last year (incidence 1.4%). All these patients had advanced-stage disease, were heavily pretreated, and received prolonged gemcitabine application, suggesting that in this subgroup of patients HUS may be more frequently encountered than documented so far.
Abstract Major histocompatibility complex class I-related chain A (MICA) molecules are frequently expressed in lymphoproliferative malignancies including multiple myeloma (MM). MICA activates NK ...cells and co-stimulates T cells by interaction with its immunoreceptor NKG2D. In contrast, soluble MICA (sMICA) molecules impair the functions of NKG2D+ T and NK cells, which may facilitate tumor cell escape from immunosurveillance. Here, we analyzed the clinical relevance of sMICA in 97 MM patients. sMICA (mean ± SEM pg/ml) was significantly increased ( p < 0.0001) in patients (429 ± 20) compared to controls (230 ± 20; N = 43). Serial determination showed a strong correlation between increments of sMICA and paraprotein levels ( r = 0.543, p < 0.0001, N = 49). sMICA levels > 305 pg/ml are associated with a poor overall ( p = 0.004) and progression-free survival ( p = 0.002). Multivariate analysis revealed sMICA as an independent predictive factor for overall ( p = 0.007) and progression-free survival ( p = 0.002). Thus, our results suggest sMICA as a potent prognostic marker in MM, which may be useful to identify risk patients.
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