Publications (46)164.94 Total impact
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Article: Molecular monitoring of minimal residual disease in the peripheral blood of patients with multiple myeloma.
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ABSTRACT: The prognostic relevance of minimal residual disease (MRD) in patients with multiple myeloma (MM) is still an open question. In the bone marrow (BM) the level of residual myeloma cells is associated with treatment outcome, but the role of clonotypic cells in the peripheral blood (PB) for the prognosis of patients is not identified yet. In this study, we retrospectively analyzed MRD by quantitative real-time IgH-PCR (IgH-qPCR) in the PB of 42 patients undergoing high-dose therapy (HDT) followed by autologous blood stem cell transplantation (PBSCT) as first-line therapy for MM. The MRD level of PB samples was in median 40-fold lower than in BM samples, collected on the same day, with a wide intra- and inter-individual variation (range: 0.4-4628 fold). The presence or absence of detectable MRD levels in PB did not correlate with the serological remission status. Still, patients with negative PCR results in PB three months after HDT and PBSCT had lower ISS stage (p=0.01), lower levels of β2-microglobulin (p=0.02), higher hemoglobin levels (p=0.01) and a prolonged event-free (median: 15 vs 4 months, p=0.004) and overall (median: 52 vs 17 months, p=0.03) survival. Importantly, by sequential monitoring of clonotypic cells in PB, in 19 of 29 patients (66 %) with progressive disease an increase of the 2IgH/ß-actin ratio of at least one log step could be detected in median 4 months (range: 0.8-13 months) before the relapse was diagnosed on the basis of the EBMT criteria. These patients with a molecular relapse in PB prior to a serological relapse had a significantly shorter OS than other patients (median: 17 months vs median not reached, p=0.02). In conclusion, IgH-qPCR is a sensitive technique for the detection of clonotypic cells in PB, which precede clinical relapse. Future studies are needed to evaluate whether these circulating tumor cells play a role in promoting disease recurrence.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2013; · 3.15 Impact Factor -
Article: Multiple myeloma-related deregulation of bone marrow-derived CD34+ hematopoietic stem and progenitor cells.
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ABSTRACT: Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. We show that hematopoietic stem and progenitor cells (HSPCs), in particular megakaryocyte-erythrocyte progenitors, are diminished in the BM of MM patients. Genomic profiling of HSPC subsets revealed deregulations of signaling cascades, most notably TGFβ signaling, and pathways involved in cytoskeletal organization, migration, adhesion, and cell-cycle regulation in the patients. Functionally, proliferation, colony formation, and long-term self-renewal were impaired as a consequence of activated TGFβ signaling. In accordance, TGFβ levels in the BM extracellular fluid were elevated and mesenchymal stromal cells (MSCs) had a reduced capacity to support long-term hematopoiesis of HSPCs that completely recovered on blockade of TGFβ signaling. Furthermore, we found defective actin assembly and down-regulation of the adhesion receptor CD44 in MM HSPCs functionally reflected by impaired migration and adhesion. Still, transplantation into myeloma-free NOG mice revealed even enhanced engraftment and normal differentiation capacities of MM HSPCs, which underlines that functional impairment of HSPCs depends on MM-related microenvironmental cues and is reversible. Taken together, these data implicate that hematopoietic suppression in MM emerges from the HSPCs as a result of MM-related microenvironmental alterations.Blood 04/2012; 120(13):2620-30. · 9.90 Impact Factor -
Article: Radiotherapie der Weichteilsarkome – Teil einer multidisziplinären Strategie
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ABSTRACT: Die Therapie der Weichteilsarkome hat einen radikalen Wandel erfahren, von einer reinen chirurgischen Tumorbehandlung hin zu einer multimodalen, interdisziplinären Therapie, unter Einbeziehung der Strahlentherapie. Die Gründe hierfür sind zum einen auf verbesserte Erkenntnisse in der Tumorbiologie, insbesondere der Strahlensensibilität und zum anderen in der technischen Weiterentwicklung der modernen Strahlentherapie zurückzuführen. Eine optimale Therapie setzt eine gute präoperative Diagnostik, eine gute Operationsplanung und ein onkologisch erfahrenes Team voraus. Maßgeblich entscheidend für die Tumorprognose ist die frühe Diagnose sowie die Tumorresektion weit im Gesunden. Auch nach kompletter Resektion senkt eine adjuvante Radiotherapie die Lokalrezidivrate signifikant und sollte bei einem Großteil der Patienten eingesetzt werden. Ein Verzicht auf die Radiotherapie ist nur bei einer Resektion allseits weit im Gesunden möglich, setzt aber eine hohe Qualität der Chirurgie sowie eine exakte histopathologische Aufarbeitung des Tumors voraus. Patienten mit primär nicht oder fraglich in sano resektablen Tumoren sollten einer präoperativen Therapie zur Verbesserung der Resektabilität zugeführt werden. Neuere Studien haben die Effektivität moderner radioonkologischer Therapie-Schemata belegt. Im Folgenden werden die entsprechenden Tumorstadien vor dem Hintergrund der Operabilität mit unterschiedlichen Therapieansätzen diskutiert. The management of soft tissue sarcoma has evolved from a solitary surgical treatment to an interdisciplinary multimodal approach including radiotherapy. These fundamental changes are the result of increased knowledge in tumor biology, radiation sensitivity and the improvement in modern radiation therapy techniques. A successful effective therapy regimen strongly depends on distinct preoperative diagnostics, preoperative conception of the surgical intervention and an experienced oncological team. Of significant importance for the prognosis is early diagnosis as well as tumor excision with a wide negative margin. However, even after complete wide resection in sano, the use of postoperative radiotherapy can further improve local control and should therefore be applied to the majority of patients. Consequently, radiotherapy should only be omitted in cases in which the tumor has been excised with a very wide negative margin; this implies, however, high quality of surgery and distinct histopathological analysis. Patients with non- or questionable resectable tumors, should be referred for pre-operative radiotherapy in order to improve the surgical results. Recent studies have underlined the efficiency of modern radiotherapy regimens. The different radiotherapy regimens will be highlighted against the background of tumor stage and tumor resectibility.Wiener klinische Wochenschrift 04/2012; 120(23):723-731. · 0.81 Impact Factor -
Article: Therapy-related myeloid neoplasms following treatment with radioiodine.
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ABSTRACT: Few data are available on therapy-related myelodysplastic syndromes and acute myeloid leukemia developing after radioiodine treatment. We retrospectively analyzed 39 patients with myeloid neoplasms following radioiodine treatment, whose data were reported to the Duesseldorf Myelodysplastic Syndromes Register (8 of 3814 patients) and five other German Myelodysplastic Syndromes centers (n=31) between 1982 and 2011. These data were compared with those from 165 patients from our Myelodysplastic Syndromes Register with therapy-related myeloid neoplasms following chemotherapy (n=90), radiation (n=30), or radiochemotherapy (n=45). With a median latency of 79 months, 18 patients developed therapy-related acute myeloid leukemia and 21 presented with therapy-related myelodysplastic syndromes (8 refractory anemia with excess blasts I/II, 6 refractory anemia with multilineage dysplasia, 3 myelodysplastic syndromes with del(5q), 1 refractory anemia, 1 refractory anemia with ring sideroblasts, 1 chronic myelomonocytic leukemia II, 1 myelodysplastic/myeloproliferative neoplasm unclassifiable). Risk assessment according to the International Prognostic Scoring System was low-risk in 23%, intermediate-1 in 29%, intermediate-2 in 35%, and high-risk in 13%. Karyotype was abnormal in 68%, with chromosomes 7 (30%), 5 (26%), 8 (26%) and 3 (17%) being most frequently affected. No differences in the distribution of gender, World Health Organization subtype, acute myeloid leukemia progression, International Prognostic Scoring System score, and cytogenetic risk were observed between patients with therapy-related myeloid neoplasms following radioiodine or other treatment modalities. Of 17 patients who received induction chemotherapy, 71% were refractory to this treatment or died from treatment-related toxicity. The median overall survival in the entire group was 21.7 months (95%-CI 10.5-33 months) and did not differ significantly in comparison to the survival of patients with therapy-related myeloid neoplasms following other cytotoxic treatments. Patients with therapy-related acute myeloid leukemia had significantly inferior overall survival (12.4 versus 28.7 months, P=0.002). Patients developing a therapy-related myeloid neoplasm after radioiodine treatment usually present with biological characteristics similar to those seen in patients with therapy-related myeloid neoplasms following other cytotoxic treatment modalities, associated with a low response rate to induction chemotherapy and poor prognosis.Haematologica 02/2012; 97(2):206-12. · 6.42 Impact Factor -
Article: Secondary primary malignancies in patients with multiple myeloma treated with high-dose chemotherapy and autologous blood stem cell transplantation.
British Journal of Haematology 11/2011; 156(5):683-6. · 4.94 Impact Factor -
Article: Upfront allogeneic blood stem cell transplantation for patients with high-risk myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based high-dose sequential conditioning regimen.
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ABSTRACT: Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor response to conventional cytotoxic chemotherapy. The purpose of our prospective single-center study was to examine the safety and efficacy of an allogeneic hematopoietic stem cell transplantation (HSCT) following a sequential conditioning regimen as first-line therapy for previously untreated patients with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA). After 2 to 3 days of rest, patients received high-dose melphalan alone (200 mg/m(2) for patients with an age <50 years, 150 mg/m(2) for patients with an age between 50 and 60 years, and 100 mg/m(2) for patients with an age >60 years; n = 24) or melphalan and thiotepa (10 mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning regimens, a median number of 7.7 × 10(6) CD34(+) cells/kg body weight (range: 2.9 × 10(6)-17.2 × 10(6)) were transplanted from 13 related or 17 unrelated donors. Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. All patients except 1 with primary graft failure achieved complete remission after HSCT. After a median follow-up time of 28 months (range: 7-81), 21 patients (70%) were alive and free of disease. Overall, 4 patients relapsed. At 2 years, overall survival, event-free survival, and treatment-related mortality were 70%, 63%, and 30%, respectively. Because of undue toxicity, thiotepa is no longer part of the conditioning regimen. Our results add to the body of evidence that a FLAMSA-based sequential conditioning therapy is effective for previously untreated patients with high-risk MDS or sAML.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2011; 18(3):466-72. · 3.15 Impact Factor -
Article: The level of minimal residual disease in the bone marrow of patients with multiple myeloma before high-dose therapy and autologous blood stem cell transplantation is an independent predictive parameter.
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ABSTRACT: The prognostic relevance of minimal residual disease (MRD) in patients with multiple myeloma is still an open question. We measured MRD levels in bone marrow (BM) samples of 53 patients treated with high-dose therapy (HDT) and autologous peripheral blood stem cell transplantation using real-time quantitative (RQ)-IgH-PCR with allel-specific oligonucleotide probes. We identified a prognostically relevant threshold level of 0.2% 2IgH/β-actin ratio in the BM before HDT. Twenty-six patients with MRD levels below this value were termed as the "low-MRD group," whereas 27 patients with levels above this threshold were allocated to the "high-MRD group." Median event-free-survival (EFS) in the low-MRD group was significantly (P = .001) longer than in the high-MRD group with 35 versus 20 months, respectively. Overall survival (OS) within the low-MRD group was also significantly longer with 70 versus 45 months (P = .04). Using multivariate analysis, we found that the pretransplantation MRD level was an independent prognostic factor for EFS (P = .003) and OS (P = .05). Further, EFS of patients in the high-MRD could be improved (P = .005) when they achieved a low MRD level after HDT. In conclusion, measuring MRD is of prognostic relevance in patients with MM, and low MRD levels should be a goal of treatment.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2011; 18(3):423-431.e3. · 3.15 Impact Factor -
Article: Predictive factors for successful salvage high-dose therapy in patients with multiple myeloma relapsing after autologous blood stem cell transplantation.
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ABSTRACT: For patients with relapsed or refractory multiple myeloma (MM) treated with a prior high-dose therapy (HDT) followed by autologous peripheral blood stem cell transplantation (PBSCT), the reapplication of HDT is a widely used salvage strategy. In this retrospective study, we report on 55 patients who were treated with salvage HDT at our institution. The conditioning regimen consisted of melphalan 200 mg/m(2) (27%), melphalan 140 mg/m(2) and busulfan 12 mg/kg body weight (40%), or melphalan 200 mg/m(2) and bortezomib 1.3 mg/m(2) (33%). Treatment-related mortality was 5% and response rates were as follows: 9% complete remission, 9% very good partial remission, 56% partial remission, 11% minimal response + stable disease, and 4% progressive disease (5% not assessable). Toxicity was moderate and the median event-free (EFS) and overall survival (OS) were 14 months and 52 months, respectively. The different conditioning regimens did not result in differences in terms of remission rates, EFS and OS, or toxicity. In multivariate analysis a duration of remission of more than 12 months after the first transplant was the only predictive factor for both EFS (p < 0.0001) and OS (p = 0.0001). In conclusion, salvage HDT followed by autologous PBSCT is an effective treatment option for patients with relapsed or refractory MM, while patients with an early relapse after their first transplant do not benefit from this treatment modality.Leukemia & lymphoma 06/2011; 52(8):1455-62. · 2.40 Impact Factor -
Article: Increased numbers of tumor-lysing monocytes in cancer patients.
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ABSTRACT: Lymphatic infiltration is a well known phenomenon in different tumors including endocrine malignancies. However, little is known about the role of antigen-presenting cells and T cell activation in this context. The aim of our study was to investigate the quantity and function of CD14+/CD56+ monocytes in tumor patients including endocrine malignancies. First, these cells were characterized in peripheral blood of endocrine and non-endocrine cancer patients as well as in tumor tissue samples. Cancer patients had in mean 3.7 times more CD14+/CD56+ monocytes in the peripheral blood compared to healthy controls (p≤0.0001), while the highest frequencies were seen in patients with heavy tumor load. Importantly, these cells additionally expressed several NK cell markers. A proof of CD14+/CD56+ infiltrations into papillary thyroid carcinoma was shown by immunohistochemical analyses. Functional analyses revealed an apoptosis inducing capacity in vitro after IFN-α re-stimulation. Our data indicate the importance of tumor-lysing monocytes in antitumor immunity.Molecular and Cellular Endocrinology 02/2011; 337(1-2):52-61. · 4.19 Impact Factor -
Article: High-dose therapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma.
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ABSTRACT: Since its introduction in 1983, high-dose therapy followed by autologous peripheral blood stem cell transplantation is a pillar of the treatment of patients with multiple myeloma. In the last decades, a multitude of clinical trials helped to improve strategies based on high-dose therapy and autologous stem cell transplantation resulting in a continuously prolongation of overall survival of patients. In this chapter we will review the progress, which has been made in order to enhance the mobilisation of autologous stem cells and increase the effectiveness of this treatment.Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 01/2011; 183:207-38. -
Article: Sorafenib treatment in 13 patients with acute myeloid leukemia and activating FLT3 mutations in combination with chemotherapy or as monotherapy.
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ABSTRACT: No abstract available.Acta Haematologica 10/2010; 124(3):153-9. · 1.35 Impact Factor -
Article: Bendamustine in patients with relapsed or refractory multiple myeloma.
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ABSTRACT: In patients with multiple myeloma, bendamustine monotherapy is effective as 1st and 2nd line therapy. However, data for patients with advanced multiple myeloma is rare. In this retrospective analysis we have identified 39 patients with relapsed or refractory multiple myeloma by means of case research, who have been treated at our institution with bendamustine as salvage therapy. After in median 2 lines of prior therapy (range: 1-5) patients received in median 3 (range: 1-10) cycles of bendamustine. Bendamustine dosage was 80-150 mg on day 1+2 of a monthly cycle. Bendamustine was administered as monotherapy in 39% of patients, whereas 61% received concomitant steroids. Toxicity was mild to moderate. Response rates were as follows: 3% vgPR, 33% PR, 18% MR, 26% SD and 20% PD. The median event-free and overall survival were 7 and 17 months, respectively. In conclusion, in patients with advanced multiple myeloma bendamustine is effective and associated with mild toxicity. Therefore, the role of bendamustine in patients with multiple myeloma should be investigated in further clinical trials.European journal of medical research 01/2010; 15(1):13-9. · 1.13 Impact Factor -
Article: Bortezomib induces erythema multiforme-like cutaneous adverse effects: report of two cases.
Wiener klinische Wochenschrift 01/2009; 121(21-22):723-4. · 0.81 Impact Factor -
Article: Unrelated umbilical cord blood transplantation as salvage treatment for engraftment failure following autologous stem cell transplantation.
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ABSTRACT: We report a case of a patient with multiple myeloma and engraftment failure after high-dose therapy with autologous stem cell transplantation. After rescue treatment with G-CSF and back-up reinfusion of autologous stem cells failed, allogeneic umbilical cord blood transplantation resulted in neutrophil engraftment on day +16 and a 57 months lasting complete remission. This case report shows that umbilical cord blood transplantation is a rescue option after engraftment failure of autologous transplantation, which is available for 99% of patients due to the less stringent HLA matching criteria. Moreover, the prompt availability allows transplantation to be performed at an optimal time.Leukemia Research 08/2008; 32(7):1157-9. · 2.92 Impact Factor -
Article: Therapy adapted to molecular response in patients with chronic myelogenous leukaemia in first chronic phase: results of the Duesseldorf study.
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ABSTRACT: This study evaluates response-adapted treatment of chronic myelogenous leukaemia (CML) in chronic phase using molecular response criteria. bcr-abl/G6PDH ratios were assessed by Light-Cycler quantitative real-time polymerase chain reaction (PCR( in 277 peripheral blood samples from 33 patients, before and every 3 months during therapy. Sixty-six per cent (22/33) of the patients fulfiled our molecular response criterion of > or = 1 log decrease in bcr-abl transcript after 6 or > or = 2 log decrease after 9 and every following 3 months. Dose escalation was necessary for 33% (11/33) of the patients. Of these, 54% (6/11) achieved a reduction of bcr-abl mRNA by > or = 2 log (n = 3) or > or = 3 log (n = 3) with 800 mg Imatinib. Forty-five per cent (5/11) showed insufficient molecular response with 800 mg Imatinib and received Nilotinib. In conclusion, the assessment of molecular response permits an individual patient-tailored treatment of CML in first chronic phase, resulting in the majority of patients achieving a major molecular response after 2 years of therapy.Hematological Oncology 05/2008; 26(4):213-8. · 2.47 Impact Factor -
Article: The sepsis-related Organ Failure Assessment (SOFA) score is predictive for survival of patients admitted to the intensive care unit following allogeneic blood stem cell transplantation.
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ABSTRACT: Intensive care unit (ICU) support following allogeneic peripheral blood stem cell transplantation (PBSCT) is controversial due to the limited prognosis of these patients in case of secondary critical illness. In this retrospective single centre study, we looked for factors predicting survival in patients who needed ICU support after myeloablative (MAC) or non-myeloablative conditioning (non-MAC) therapy and allogeneic PBSCT. Between 1999 and 2006, 64 out of 319 patients following allogeneic PBSCT were admitted to the ICU (24 female and 40 male patients, median age 47 years, range 17-65 years; MAC 49 patients, non-MAC 15 patients). All 64 patients required mechanical ventilation. We looked for variables defining the Sepsis-related Organ Failure Assessment (SOFA) score as well as for baseline characteristics and transplant-associated parameters on the day of ICU admission possibly predictive for poor or good survival prognosis. Nineteen of 49 patients who had received MAC therapy survived the ICU stay for a median time of 9 months (range 2-29 months) and three of 15 patients who had received non-MAC therapy could be discharged from the ICU with a survival time of 4, 5 and 12 months. After univariate and multivariate analysis the SOFA score discriminated survivors and non-survivors of the ICU stay. We conclude that the SOFA score is predictive for survival when applied on the day of ICU admission.Annals of Hematology 05/2008; 87(4):299-304. · 2.62 Impact Factor -
Article: Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor.
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ABSTRACT: Pegylated granulocyte colony-stimulating factor (G-CSF) has recently been introduced as a new compound for mobilization of CD34(+) hematopoietic stem and progenitor cells. In this study, we compared the molecular and functional characteristics of CD34(+) cells mobilized by pegylated G-CSF with those mobilized by unconjugated G-CSF. Gene expression of immunomagnetically enriched CD34(+) cells from leukapheresis products of patients who were given pegylated-G-CSF or unconjugated G-CSF was analyzed using Affymetrix HG Focus microarrays and quantitative reverse transcriptase polymerase chain reaction. Flow cytometry and fluorescence activated cell sorting was conducted to assess the CD34(+) subset composition and to obtain Lin(-), CD34(+), CD38(-) hematopoietic stem cells. Cell cycle assays and clonogenic assays were performed for functional corroboration. Pegylated G-CSF and unconjugated G-CSF mobilized CD34(+) and hematopoietic stem cells with different molecular phenotypes and functional properties. The CD34(+) cells mobilized by pegylated G-CSF had higher expression levels of genes indicative of early hematopoiesis, including HOXA9, MEIS1 and GATA3. We found lower expression of genes characteristic of erythroid and later stages of myeloid differentiation and a lower functional burst-forming unit erythroid/colony-forming unit-granulocyte-macrophage ratio. Consistently, greater numbers of hematopoietic stem cells and common myeloid progenitors and fewer megakaryocyte-erthrocyte progenitors were found in the pegylated-G-CSF-mobilized CD34(+) cells. Additionally, sorted pegylated-G-CSF-mobilized hematopoietic stem cells displayed higher expression of HOXA9 in comparison to G-CSF-mobilized hematopoietic stem cells. In line with the gene expression data, CD34(+) cells mobilized by pegylated G-CSF, as well as sorted hematopoietic stem cells, showed a significantly greater cell cycle activity. Stimulation with pegylated-G-CSF or G-CSF results in different expression of key regulatory genes and different functional properties of mobilized hematopoietic stem cells as well as their progeny, a finding that might be relevant for the application of these cells in blood stem cell transplantation.Haematologica 04/2008; 93(3):347-55. · 6.42 Impact Factor -
Article: IFN-alpha skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo.
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ABSTRACT: The antitumor effect of IFN-alpha is mediated by the activation of CTLs, NK cells, and the generation of highly potent Ag-presenting dendritic cells (IFN-DCs). In this study, we show that IFN-DCs generated in vitro from monocytes express CD56 on their surface, a marker which has been thought to be specific for NK cells. FACS analyses of CD56(+) and CD56(-) IFN-DCs showed a nearly identical pattern for most of the classical DC markers. Importantly, however, only CD56(+) IFN-DCs exhibited cytolytic activity up to 24% that could almost completely be blocked (-81%) after coincubation with anti-TRAIL. Intracytoplasmatic cytokine staining revealed that the majority of IFN-DCs independently of their CD56 expression were IFN-gamma positive as well. In contrast, CD56(+) IFN-DCs showed stronger capacity in stimulating allogenic T cells compared with CD56(-) IFN-DC. Based on these results, five patients with metastasized medullary thyroid carcinoma were treated for the first time with monocyte-derived tumor Ag-pulsed IFN-DCs. After a long term follow-up (in mean 37 mo) all patients are alive. Immunohistochemical analyses of delayed-type hypersensitivity skin reaction showed a strong infiltration with CD8(+) cells. In two patients no substantial change in tumor morphology was detected. Importantly, by analyzing PBMCs, these patients also showed an increase of Ag-specific IFN-gamma-secreting T cells. In summary, we here describe for the first time that cytotoxic activity of IFN-DCs is mainly mediated by an IFN-DC subset showing partial phenotypic and functional characteristics of NK cells. These cells represent another mechanism of the antitumor effect induced by IFN-alpha.The Journal of Immunology 03/2008; 180(3):1462-70. · 5.79 Impact Factor -
Article: [Radiotherapy of soft tissue sarcoma--part of a multidisciplinary strategy].
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ABSTRACT: The management of soft tissue sarcoma has evolved from a solitary surgical treatment to an interdisciplinary multimodal approach including radiotherapy. These fundamental changes are the result of increased knowledge in tumor biology, radiation sensitivity and the improvement in modern radiation therapy techniques. A successful effective therapy regimen strongly depends on distinct preoperative diagnostics, preoperative conception of the surgical intervention and an experienced oncological team. Of significant importance for the prognosis is early diagnosis as well as tumor excision with a wide negative margin. However, even after complete wide resection in sano, the use of postoperative radiotherapy can further improve local control and should therefore be applied to the majority of patients. Consequently, radiotherapy should only be omitted in cases in which the tumor has been excised with a very wide negative margin; this implies, however, high quality of surgery and distinct histopathological analysis. Patients with non- or questionable resectable tumors, should be referred for pre-operative radiotherapy in order to improve the surgical results. Recent studies have underlined the efficiency of modern radiotherapy regimens. The different radiotherapy regimens will be highlighted against the background of tumor stage and tumor resectibility.Wiener klinische Wochenschrift 02/2008; 120(23-24):723-31. · 0.81 Impact Factor -
Article: Escalation therapy with bortezomib, dexamethasone and bendamustine for patients with relapsed or refractory multiple myeloma.
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ABSTRACT: In order to improve remission rates without causing undue toxicity, we treated 50 patients with relapsed/refractory multiple myeloma according to an institutional sequential treatment algorithm. Bortezomib was given as monotherapy (1.3 mg/m(2) on day 1 + 4 + 8 + 11) followed by the addition of dexamethasone in a first (40 mg on day 1 + 4 + 8 + 11) and bendamustine (50 - 100 mg/m(2) on day 1 + 8) in a second escalation step for patients with less than a minor response. Bortezomib monotherapy was sufficient in 23 (46%) patients, treatment escalation with dexamethasone was necessary in 20 (40%) patients and 7 (14%) patients needed triple combination therapy. Overall response rate was 84% while toxicity was manageable. Median time to progression and overall survival were 8 and 20 months, respectively. In conclusion, this treatment algorithm resulted in responses in the majority of heavily pre-treated patients while at the same time restricting the toxicity of triple combination therapy to only 14% of non-responding patients.Leukemia and Lymphoma 01/2008; 48(12):2345-51. · 2.58 Impact Factor
Top co-authors
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Institutions
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2002–2012
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Heinrich-Heine-Universität Düsseldorf
- Klinik für Hämatologie, Onkologie und Klinische Immunologie
Düsseldorf, North Rhine-Westphalia, Germany
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2006–2011
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Universitätsklinikum Düsseldorf
- Endocrine Cancer Centre
Düsseldorf, North Rhine-Westphalia, Germany
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