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A Ganser

Publications and source records attributed to A Ganser.

At least 19 recordsLinked to original sources
PubMed2006

Initial chemotherapy with mitoxantrone, chlorambucil, prednisone impairs the collection of stem cells in patients with indolent lymphomas--results of a randomized comparison by the German Low-Grade Lymphoma Study Group.

Myeloablative radio-chemotherapy with subsequent autologous stem cell transplantation (ASCT) significantly prolongs progression free and probably overall survival in follicular lymphoma (FL) in first remission. The current trial explored prospectively the rate of successful stem cell mobilization in patients with advanced stage FL after initial therapy with either Mitoxantrone, Chlorambucil, Prednisone (MCP) or Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) as part of a prospective randomized comparison of both regimens. ASCT patients received Dexa-BEAM (Dexamethasone, BCNU, Melphalan, Etoposide, Cytarabine) for mobilization of stem cells. Stem cells were collected and a minimum of 2x2.0x106/kg bw CD34+ was required for ASCT. Of 79 evaluable patients, 58 (73%) had follicular lymphoma, 13 (16%) mantle cell lymphoma and 8 (10%) lymphoplasmacytic lymphoma. In the 45 patients assigned to CHOP, stem cell collection was successful in 42 cases (93%, 95% CI 82% to 99%). This high mobilization rate after CHOP could be confirmed in 61 subsequent patients (87%). In contrast, after MCP therapy stem cell collection was successful in only 15 of 34 patients (44%, 95% CI 27% to 62%; P=0.0003). In conclusion, initial therapy with MCP significantly impairs the ability to collect stem cells and should be avoided for first line therapy of younger patients potentially qualifying for high dose consolidation and ASCT in first remission.

Adult↗
PubMed2006

Regulatory T-cells in the control of immunological diseases.

The immune system is challenged by randomly generated immune receptors that by chance can recognize self-antigens. Immunological tolerance functions as a fundamental concept in the control of a broad spectrum of immune responses not only to autoantigens but also to foreign antigens. During the past decade, CD4+ CD25+ regulatory T-cells (Tregs) have emerged as key players in the development of immunological tolerance. This review will present an update on the current knowledge about the phenotype, function, and clinical relevance of this regulatory T-cell population. The therapeutical potential of Tregs to specifically suppress immune responses in autoimmunity and transplantation and their inhibitory effects in anti-tumor immune responses will be discussed.

Animals↗
PubMed2006

Long-term survival data from a phase 3 study of Filgrastim as an adjunct to chemotherapy in adults with de novo acute myeloid leukemia.

We previously reported the results of a double-blind, placebo-controlled study of Filgrastim in patients with de novo AML undergoing induction and consolidation chemotherapy. The study demonstrated that Filgrastim was effective and well tolerated and had no impact on complete remission or survival. We now report follow-up data on these patients, assessing long-term effects with emphasis on prognostic indicators. After a median follow-up of 7 years, 434 (83%) patients were dead, 73 (14%) were alive, and 14 (3%) were lost to follow-up. The proportions of deaths were similar in the Filgrastim (83%) and placebo (84%) groups. No differences in median time to death (1.04 years Filgrastim, 1.13 years placebo; P = 0.97) or median disease-free survival (0.86 years Filgrastim, 0.79 years placebo; P = 0.52) were evident. Proportional hazard modeling identified age, performance status, and French-American-British subtype as independent predictors for survival (P < 0.001, P = 0.005, and P = 0.036, respectively), whereas cytogenetic status was not (P = 0.118). Filgrastim had no effect on overall survival in any of these subgroup analyses as none of the treatment comparisons were statistically significant. These findings indicate that Filgrastim can be effectively used to support patients with AML undergoing induction and consolidation chemotherapy without worsening long-term disease outcome.

Acute Disease↗
PubMed2005

Weekly 24 h infusion of aviscumine (rViscumin): a phase I study in patients with solid tumours.

Aviscumine is a ribosome-inactivating protein with potent antitumour activity in vitro and in vivo and is an Escherichia coli-derived recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a prolonged infusion of aviscumine in cancer patients. Aviscumine was given once weekly as a 24 h central intravenous infusion in patients with advanced, refractory progressive solid malignant tumours. Fourteen fully eligible patients (11 male, 3 female) with a median age 58 yrs (range 41-77) were enrolled. They had histologically verified disease, were 18 yrs old, had an ECOG PS 2 and adequate bone marrow, liver and renal function. DLT was defined as any non-haematological grade 3-4 toxicity (Common Toxicity Criteria [CTC] version 2.0), neutrophil count <500/ microl for 7 days, febrile neutropenia or thrombocytopenia grade 4. The MTD was defined as the dose level below the dose at which 2 patients per dose level experienced a DLT during the first treatment cycle. Colorectal cancer, soft tissue sarcoma and pancreatic cancer were the most common tumour types. Dose levels of aviscumine ranged from 4 to 6 microg/kg. The median number of cycles was 2.8 (range, 2-8). Common side effects in cycle 1 were fatigue, fever, nocturia, urticaria, erythema and pruritus. DLTs occurred in 2/3 patients on the 6 microg/kg dose level and consisted of increases in ASAT grade 3, ALAT grade 3, gammaGT grade 3/4, hypokalemia grade 3 and fatigue grade 3. No DLTs were observed on dose levels 4 and 5 microg/kg. The best response (RECIST) was stable disease in 4 pts, lasting for 4-8 cycles. Pharmacokinetics indicated that potentially active plasma levels of the compound were maintained during the entire infusion. We conclude that the recommended dose for weekly 24 h infusions of Aviscumine should be 5 microg/kg.

Adult↗
PubMed2005

Stable RNA interference (RNAi) as an option for anti-bcr-abl therapy.

RNA interference (RNAi) has recently been used for sequence-specific gene silencing of disease-related genes including oncogenes in hematopoietic cells. To characterize its potential therapeutic value, we analyzed different modes to activate RNAi as well as some pharmacokinetic aspects of gene silencing in bcr-abl+ cells. Using lentiviral gene transfer of transcription cassettes for anti-bcr-abl shRNAs and red fluorescence protein (RFP) as a quantitative reporter, we demonstrate that stable but not transient RNAi can efficiently deplete bcr-abl+ K562 and murine TonB cells from suspension cultures. Importantly, depletion of bcr-abl+ cells depends on the dose of lentivirus used for transduction and correlates with the RFP-expression level of transduced target cells: RFP-high K562 cells are eradicated, whereas RFP-low or -intermediate cells may recover after prolonged cell culture. Interestingly, these cells still show reduced bcr-abl mRNA levels, aberrant proliferation kinetics, and enhanced sensitivity to the Bcr-Abl-kinase inhibitor STI571. Quantitative PCR from genomic DNA suggests that more than three lentiviral integrations are required for effective depletion of K562 cells. Finally, we demonstrate that lentivirus-mediated anti-bcr-abl RNAi can inhibit colony formation of primary CD34+ cells from chronic myeloid leukemia patients. These data demonstrate dose-dependent gene silencing by lentivirus-mediated RNAi in bcr-abl+ cells and suggest that stable RNAi may indeed be therapeutically useful in primary hematopoietic cells.

Animals↗
PubMed2005

Anodic plasma chemical treatment of titanium Schanz screws reduces pin loosening.

OBJECTIVE: This study was designed to assess the benefits of a new Anodic Plasma Chemical calcium-phosphate (APC-CaP) surface treatment on reducing pin track infection and pin loosening in comparison to anodized titanium (Ti) during external fracture fixation. METHODS: A tibial midshaft, transverse, 6-mm gap osteotomy was created in 17 adult female Swiss alpine sheep. The tibia was stabilized with an external fixator and 4 Schanz screws of Ti or APC-CaP-treated Ti. The sheep were examined during a 12-week observation period. Infection was assessed with weekly clinical pin track grading and microbiologic assessment at sacrifice. Pin loosening was assessed by grading for radiolucency on biweekly radiographs and by measuring extraction torque on pin removal. In vivo bending stiffness measurements were performed to determine gap healing. A qualitative histologic assessment of the tissue adjacent to pin sites was also performed. RESULTS: A trend (P = 0.056) for less infection around APC-CaP pins was found at 6 weeks, but the strength of this difference diminished with time. Significantly more radiolucency was found around Ti pins after 8 (P = 0.011) and 12 (P < 0.001) weeks. At all pin sites, the extraction torque for APC-CaP pins was higher than for Ti pins (P = 0.007). No difference in the progression of gap healing was found. Histology showed bone growth at the implant surface in the form of distance osteogenesis for Ti and contact osteogenesis for APC-CaP. CONCLUSIONS: This study has shown that the APC-CaP surface improves the clinical performance of Ti pins with respect to pin loosening and pin track infection.

Animals↗
PubMed2004

[The competence network "acute and chronic leukemias"].

Leukemias are a challenge and a cost factor to society because of their frequency in all age groups. They also serve as a model for a variety of diseases and possess exemplary relevance for basic research and patient care. Leukemia research and therapy have achieved high standards and even a leading position in Germany with regard to clinical trials, standardization of diagnostics and molecular studies of prognostic factors, signal transduction and gene expression. Progress is hampered, however, by fragmentation of leukemia trial groups, diagnostic approaches and treatment research activities. A network was therefore created to integrate the leading leukemia trial groups on chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphatic leukemia (ALL), myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (CMPD) and their interdisciplinary partners (diagnostics, treatment research, biometry) in cooperation with basic research and pharmaceutical industry to foster advancements in leukemia-related research and health care through clinical trials, promotion of translational research, introduction of standards for diagnostics and therapy, and development of evidence-based guidelines. Achievements include establishment of central information, communication and management structures, creation of an AML intergroup comprising five study groups, formation of a myelodysplastic syndromes study group and establishment of platforms for diagnostics, genomics and proteomics, and medical informatics. Exchange of scientific progress is mediated by intra- and internet, bi-annual newsletters, regular project group meetings and annual network symposia. Already now, the network structures leukemia therapy and research in Germany and supports the spread of scientific excellence in the field of leukemias.

Acute Disease↗
PubMed2004

Reduction of catheter-related infections in neutropenic patients: a prospective controlled randomized trial using a chlorhexidine and silver sulfadiazine-impregnated central venous catheter.

Antiseptic coating of intravascular catheters may be an effective means of decreasing catheter-related colonization and subsequent infection. The purpose of this study was to assess the efficacy of chlorhexidine and silver sulfadiazine (CH-SS)-impregnated central venous catheters (CVCs) to prevent catheter-related colonization and infection in patients with hematological malignancies who were subjected to intensive chemotherapy and suffered from severe and sustained neutropenia. Proven CVC-related bloodstream infection (BSI) was defined as the isolation of the same species from peripheral blood culture and CVC tip (Maki technique). This randomized, prospective clinical trial was carried out in 106 patients and compared catheter-related colonization and BSI using a CH-SS-impregnated CVC (n=51) to a control arm using a standard uncoated triple-lumen CVC (n=55). Patients were treated for acute leukemia (n=89), non-Hodgkin's lymphoma (n=10), and multiple myeloma (n=7). Study groups were balanced regarding to age, sex, underlying diseases, insertion site, and duration of neutropenia. The CVCs were in situ a mean of 14.3+/-8.2 days (mean+/-SD) in the study group versus 16.6+/-9.7 days in the control arm. Catheter-related colonization was observed less frequently in the study group (five vs nine patients; p=0.035). CVC-related BSI were significantly less frequent in the study group (one vs eight patients; p=0.02). In summary, in patients with severe neutropenia, CH-SS-impregnated CVCs yield a significant antibacterial effect resulting in a significantly lower rate of catheter-related colonization as well as CVC-related BSI.

Bacteremia↗
PubMed2004

Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup.

PURPOSE: To evaluate prognostic factors for relapse-free survival (RFS) and overall survival (OS) and to assess the impact of different postremission therapies in adult patients with core binding factor (CBF) acute myeloid leukemias (AML). PATIENTS AND METHODS: Individual patient data-based meta-analysis was performed on 392 adults (median age, 42 years; range, 16 to 60 years) with CBF AML (t(8;21), n = 191; inv(16), n = 201) treated between 1993 and 2002 in prospective German AML treatment trials. RESULTS: RFS was 60% and 58% and OS was 65% and 74% in the t(8;21) and inv(16) groups after 3 years, respectively. For postremission therapy, intention-to-treat analysis revealed no difference between intensive chemotherapy and autologous transplantation in the t(8;21) group and between chemotherapy, autologous, and allogeneic transplantation in the inv(16) group. In the t(8;21) group, significant prognostic variables for longer RFS and OS were lower WBC and higher platelet counts; loss of the Y chromosome in male patients was prognostic for shorter OS. In the inv(16) group, trisomy 22 was a significant prognostic variable for longer RFS. For patients who experienced relapse, second complete remission rate was significantly lower in patients with t(8;21), resulting in a significantly inferior survival duration after relapse compared with patients with inv(16). CONCLUSION: We provide novel prognostic factors for CBF AML and show that patients with t(8;21) who experience relapse have an inferior survival duration.

Acute Disease↗
PubMed2004

Activation of protein kinase A (PKA) by 8-Cl-cAMP as a novel approach for antileukaemic therapy.

Activation of PKA by cAMP agonists, such as 8-Cl-cAMP activation, selectively causes rapid apoptosis in v-abl transformed fibroblasts by inhibiting the Raf-1 kinase. Here we investigated whether 8-Cl-cAMP is useful for the treatment of chronic myelogenous leukaemia (CML), which is hallmarked by the expression of the p210(bcr/abl) oncogene. Autologous bone marrow transplantation is a feasible alternative for patients with no suitable donor, but hampered by the risk of relapse due to the persistence of leukaemia cells in the transplant. To study the effects of 8-Cl-cAMP on primary leukaemic cells, bone marrow cells (BMCs) from eight CML patients (one at diagnosis, three in chronic and four in accelerated phase) were treated. Ex vivo treatment of BMCs obtained in chronic phase of CML with 100 microM 8-Cl-cAMP for 24-48 h led to the selective purging of Philadelphia Chromosome (Ph1 chromosome) without toxic side effects on BMCs from healthy donors as measured by colony-forming unit (CFU) assays. BMCs from patients in accelerated phase showed selective, but incomplete elimination of Ph1 chromosome positive colony forming cells. The mechanism of 8-Cl-cAMP was investigated in FDCP-mix cells transformed by p210(bcr/abl), a cell culture model for CML. The results showed that 8-Cl-cAMP reduced DNA synthesis and viability independent of Raf inhibition as Raf inhibitors had no effect. MEK inhibitors interfered with DNA synthesis, but not with viability. In summary, our results indicate that 8-Cl-cAMP could be useful to purge malignant cells from the bone marrow of patients with CML and certain other forms of leukaemias.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2004

Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia.

In an attempt to improve the complete remission (CR) rates and to prolong the remission duration especially in elderly patients > 50 years of age, we have used a combination chemotherapy of idarubicin (10 mg/m2 IV x 3 days), cytarabine (AraC, 100 mg/m2 CIVI x 7d), and etoposide (100 mg/m2 x 5 days) in combination with granulocyte colony-stimulating factor (G-CSF) priming [5 mg/kg SQ day 1 until absolute neutrophil count (ANC) recovery] for remission induction. Responding patients received two consolidation courses of idarubicin, AraC, and etoposide, followed by a late consolidation course of intermediate-dose AraC (600 mg/m2 IV every 12 h x 5 days) and amsacrine (60 mg/m2 IV x 5 days). A total of 112 patients (57 male/55 female) with a median age of 58 years (range: 22-75) have been entered and are evaluable for response: 19 refractory anemia with excess of blast cells in transformation (RAEB-T), 84 acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS), and 9 secondary AML after chemotherapy/radiotherapy. The overall CR rate was 62%, partial remission (PR) rate 10%, treatment failure 16%, and early death rate 12%. The CR rate was higher in patients < or = 60 years (68 vs 55%), mainly due to a lower early death rate (5 vs 21%, p<0.001). After a median follow-up of 58 months, the median overall survival is 14.5% and median duration of relapse-free survival 8 months. After 60 months, the probability of CR patients to still be in CR and alive is 16% (20% in patients < or = 60 years and 13% in patients >60 years), while the probability of overall survival is 12% (15% in patients < or = 60 years and 9% in patients > 60 years). Compared to our previous trial (AML-MDS Study 01-92) which was done with identical chemotherapy but no G-CSF priming in 110 patients with RAEB-T, AML after MDS, or secondary AML (identical median age, age range, and distribution of subtypes), the CR rate in all patients, as well as CR rate, overall survival, and relapse-free survival in patients > 60 years have significantly been improved. Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly effective for remission induction in these high-risk patients.

Acute Disease↗
PubMed2004

Risk-adapted induction and consolidation therapy in adults with de novo AML aged </= 60 years: results of a prospective multicenter trial.

We treated 305 de novo acute myeloid leukemia (AML) patients aged </=60 years with risk-adapted therapy. Patients with CBF leukemias or normal karyotype and good response to induction I [</=5% bone marrow (BM) blasts on day 15] were considered standard risk (SR), all others as high risk (HR). Patients with t(15;17) were excluded. Chemotherapy comprised double induction followed by early consolidation. As late consolidation, SR patients received high-dose cytarabine/daunorubicin (AraC/DNR). SR patients with normal karyotype were allotransplanted from HLA-matched siblings. HR patients were allotransplanted or if no sibling donor was available autotransplanted with peripheral blood progenitor cells (PBSC) harvested after early consolidation. 89% of the SR and 60% of the HR patients achieved CR. The continuous complete remission (CCR) rate at 80 months (median follow-up: 48 months) was 48% for SR and 32% for HR. The CCR rate was 54% for t(8;21), 47% for normal karyotype, and 33% for inv(16) patients. In the HR group, the CCR rate did not differ significantly for patients with bad response to IVA-I, unfavorable karyotype, or both. Forty-five HR patients were autotransplanted (n=20) or allotransplanted (n=25). The probability of CCR was 44% for autotransplantation vs 33% for allotransplantation. In conclusion, our risk-adapted strategy produced encouraging results in SR patients. Early response to therapy is a strong prognostic factor that predicts the probability of CR and long-term outcome.

Adolescent↗
PubMed2004

[Clinical research in the "acute and chronic leukemias"competence network ].

Goal of the network is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among all major groups in Germany that deal with the leukemias in research and in patient care. In practice, cooperation between clinical groups and scientists in research institutes is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation and also increase information transfer from top research institutions to clinical translation. The network comprises more than 1400 participants in about 400 university centers, large community hospitals and specialty practices with functional communication structures, interdisciplinary cooperation and nation-wide logistics. The improved cooperation and the accelerated information transfer from the bench to the "bedside" results in an added value that ultimately results in improved survival results of patients and in superior competitiveness of involved research workers and clinicians. Sustainability is addressed by establishing a leukemia foundation to support long term financial coverage of the network and by negotiating a proposal for a European Network of Excellence against leukemia within the Sixth Framework Programme of the European Union.

Acute Disease↗
PubMed2004

[Bone marrow transplantation. Indications, chances and perspectives].

The hematopoietic stem cell transplantation has become an essential part of the treatment regimens in patients with acute and chronic leukemias, myelodysplastic syndromes, malignant lymphomas, multiple myeloma, and aplastic anemia. The decision to transplant depends on the stage of the disease, presence of risk factors, and age of the patient and should be taken by experienced hematologists/oncologists. Advances in immunogenetics have improved the treatment results of unrelated marrow donor transplantations. Better supportive care, modified conditioning regimens, and special graft preparations allow an allogeneic transplantation up to an age of 60 to 65 years, an autologous transplantation at an even higher age.

Anemia, Aplastic↗
PubMed2004

A prospective, randomised, phase II study of horse antithymocyte globulin vs rabbit antithymocyte globulin as immune-modulating therapy in patients with low-risk myelodysplastic syndromes.

Immunosuppression has recently been proposed for low-risk myelodysplastic syndromes (MDS) to reverse bone marrow failure by inhibiting intramedullary secretion of proapoptotic cytokines. We treated 35 MDS patients (24 refractory anaemia (RA), 10 RA with excess blasts and one chronic myelomonocytic leukaemia) with either horse antithymocyte globulin 15 mg/kg/day or rabbit antithymocyte globulin 3.75 mg/kg/day, each for 5 days. Median age was 63 years (range: 41-75). After 1 to 34+ months of follow-up (mean: 15+), four patients experienced complete haematological responses (CR), six good responses (GR) and two minor responses. All CRs and GRs occurred in patients with RA, in whom both horse and rabbit ATG yielded five responses out of 12 (42%). Time to response varied between 1 and 10 (mean: 3) months. The median duration of response was 9+ (1-17+) months; five patients are in continuing response. In all, 23 patients suffered side effects > degrees II WHO (the degree of toxicity encountered according to the internationally accepted WHO toxicity grading); one patient died 2 weeks after rabbit ATG from rhinocerebral mucormycosis. Parameters that correlated with response were duration of disease and RA subgroup. In our experience, immune-modulating therapy with either horse or rabbit ATG is feasible in patients with RA and short duration of disease.

Adult↗
PubMed2004

Expression of the p14ARF tumor suppressor predicts survival in acute myeloid leukemia.

Cell cycle aberrations are associated with therapy outcome in many types of cancer. We analyzed mRNA expression levels of 18 cell cycle-related genes in bone marrow samples from 78 acute myeloid leukemia (AML) patients and six controls using high-throughput quantitative RT-PCR. Samples of AML patients contained significantly increased mRNA expression levels of the mdm2 and c-myc oncogenes. Also, the average expression levels of p14ARF and p16INK4A were higher in patient samples compared to controls. Leukemic blasts and control bone marrow samples did not differ significantly in the expression levels of proliferation-associated genes such as cyclin A2 and pcna. When single genes were analyzed for prognostic significance in Kaplan-Meier and Cox regression analyses, a low p14ARF level emerged as a strong and independent predictor for poor survival (P=0.04 and 0.029). Subsequently, p14ARF mRNA levels were analyzed in a second, independent patient population (n=57). Again, low p14ARF levels were associated with a worse outcome. Finally, immunohistochemistry analysis of AML tissue arrays confirmed the widespread expression of c-myc and p14ARF in AML on the protein level. Taken together, the expression of the p53 regulators mdm2 and p14ARF are altered in AML, and low p14ARF levels indicate a poor prognosis.

Acute Disease↗