Ingo G H Schmidt-Wolf

Centrum für Integrierte Onkologie, Köln, North Rhine-Westphalia, Germany

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Publications (285)1351.11 Total impact

  • C Ziske · T Schmidt · M Gorschlüter · V Schmitz · T Sauerbruch · I Schmidt-Wolf
    Zeitschrift für Gastroenterologie 08/2015; 41(08). DOI:10.1055/s-0035-1555329 · 1.05 Impact Factor
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    ABSTRACT: Treatment options for patients with relapsed and refractory multiple myeloma have improved since the introduction of immune-modulating agents such as lenalidomide and thalidomide. However, almost all patients relapse and suffer from an increasing amount of adverse events due to multiple lines of therapy that eventually lead to a reduced quality of life. In this bicentric retrospective analysis, 58 patients who had been treated with either bendamustine monotherapy (62 % of the patients) or combined steroid therapy were included. Further inclusion criteria were at least relapsed disease. Patients had previously been treated with a mean of four lines of therapy (range 1-10). They received a median of three cycles of treatment. Dosage varied from 60 to 300 mg/m(2) (median 120 mg/m(2)) and was administered intravenously on day 1 and 2 of a 28-day cycle. Observed toxicity was mild and most commonly led to hematological side effects such as thrombopenia and anemia. Response rates were as follows: no complete response, 20 % partial response, 39 % minimal response, 27 % stable disease and 14 % progressive disease. Median overall survival (OS) was 17 months. Median event-free survival was 7 months. Patients who had not received a concomitant steroid had a median OS of 17 months compared to 13 months median OS for patients who had received a concomitant steroid. Bendamustine monotherapy is an effective treatment option for heavily pre-treated myeloma patients due to its favorable response rate and mild toxicity.
    Journal of Cancer Research and Clinical Oncology 07/2015; DOI:10.1007/s00432-015-2014-2 · 3.08 Impact Factor
  • Young Kim · Ingo Schmidt-Wolf
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    ABSTRACT: Neue Präparate in Kombination mit klassischen ermöglichen ein verbessertes Ansprechen bei reduzierten Nebenwirkungen. Die Frage nach der optimalen Therapie wird intensiv diskutiert.
    Deutsches Ärzteblatt 05/2015; DOI:10.3238/PersOnko.2015.05.15.08 · 3.61 Impact Factor
  • Young Kim · Ingo G H Schmidt-Wolf
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    ABSTRACT: In 1994, the first clinical gene therapy trial was performed in Germany. Since then more than 2000 clinical gene therapy trials have been performed worldwide. After 20 years, a short résumé is drawn here. © Georg Thieme Verlag KG Stuttgart · New York.
    DMW - Deutsche Medizinische Wochenschrift 04/2015; 140(9):684-686. DOI:10.1055/s-0041-101663 · 0.54 Impact Factor
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    ABSTRACT: We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML-Study IV, a randomized five-arm trial designed to optimize imatinib therapy were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI). 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were: CCI 2: n=589, CCI 3 or 4: n=599, CCI 5 or 6: n=229, and CCI ≥ 7: n=102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4%, for patients with CCI 2, 3-4, 5-6 and ≥ 7. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as outcome measure for specific CML treatments. Copyright © 2015 American Society of Hematology.
    Blood 04/2015; 126(1). DOI:10.1182/blood-2015-01-617993 · 10.45 Impact Factor
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    ABSTRACT: We investigated impact of subcutaneous versus intravenous bortezomib in the MM5 trial of the German-Speaking Myeloma Multicenter Group that compared bortezomib, doxorubicin, dexamethasone with bortezomib, cyclophosphamide, dexamethasone induction therapy in newly diagnosed multiple myeloma. Based on the data in relapsed myeloma, the route of administration for bortezomib was changed from intravenous to subcutaneous after 314 of 604 patients were enrolled. We analyzed 598 patients who received at least one dose of trial medication. Adverse events were reported more frequently in patients treated with intravenous bortezomib (intravenous=65%; subcutaneous=56%, p=0.02). Rates of peripheral neuropathy ≥ grade 2 were higher in patients treated with intravenous bortezomib during the third cycle (intravenous=8%; subcutaneous=2%, p=0.001). Overall response rates were similar in intravenously and subcutaneously treated patients. Presence of international staging system stage III, renal impairment or adverse cytogenetic abnormalities had no negative impact on overall response rates in both groups. This is to our knowledge the largest study to present data comparing subcutaneous with intravenous bortezomib in newly diagnosed myeloma. We show better tolerance and similar overall response rates for subcutaneous compared to intravenous bortezomib. The clinical trial is registered at as No. 2010-019173-16. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 04/2015; 100(7). DOI:10.3324/haematol.2015.124347 · 5.81 Impact Factor
  • Journal of Hepatology 04/2015; 62:S397. DOI:10.1016/S0168-8278(15)30458-X · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S391-S392. DOI:10.1016/S0168-8278(15)30444-X · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S404-S405. DOI:10.1016/S0168-8278(15)30478-5 · 11.34 Impact Factor
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    ABSTRACT: Intensive therapy regimens in patients with acute myeloid leukemia (AML) frequently result in sepsis and septic shock. In this study, we investigated the prognostic outcome of AML patients requiring intensive care treatment due to severe sepsis or septic shock. We present a retrospective cohort study in a medical intensive care unit (ICU) of a university hospital that serves as a tertiary care center. Here we present data from 44 AML patients of our ICU with 29 requiring invasive mechanical ventilation due to sepsis and compared multiple clinical and laboratory parameters of ICU survivors and non-survivors. Mean age was 59.5 years, the overall mortality rate was 41 % (18/44), and the mortality rate among patients who received mechanical ventilation was 55 % (16/29). The mortality rate among younger patients (aged 60 years or less) was 17 % (3/18), while 58 % of the older patients died (15/26). The mortality rate among younger patients who received mechanical ventilation was 23 % (3/13) compared with 81 % (13/16) of the older patients. The mean invasive ventilation time was 415 h in non-survivors compared with 667 h in survivors. No differences could be identified between survivors and non-survivors, concerning multiple laboratory parameters or AML prognostic and therapeutic parameters; our analysis, however, confirmed a statistically significant difference in the patients' age. In previous studies, age was one of the most important prognostic factors in AML patients receiving mechanical ventilation due to severe sepsis or septic shock. In spite of improvements in diagnostic and treatment over the last couple of years, our study indicates that this fact still is true. However, the overall outcome has improved over the years due to improvements in intensive care medicine.
    Journal of Cancer Research and Clinical Oncology 03/2015; 141(9). DOI:10.1007/s00432-015-1955-9 · 3.08 Impact Factor
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    ABSTRACT: We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial response rates or better (≥VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma (MM) patients. VCD was found to be non-inferior to PAd with respect to ≥VGPR rates (37.0% vs. 34.3%, p=0.001). The rates of progressive disease (PD) were 0.4% (VCD) vs. 4.8% (PAd) (p=0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ≥2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leucocytopenia/neutropenia (≥3°) occurred more frequently in the VCD arm (35.2% vs. 11.3%, p<0.001). Neuropathy rates (≥2°) were higher in the PAd group (14.9% vs. 8.4%, p=0.03). Serious Adverse Events (SAEs), both overall and those related to thromboembolic events, were higher in the PAd group (32.7% vs. 24.0%, p=0.04 and 2.8% vs. 0.4%, p=0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ≥VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy.Leukemia accepted article preview online, 19 March 2015. doi:10.1038/leu.2015.80.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2015; 29(8). DOI:10.1038/leu.2015.80 · 10.43 Impact Factor
  • Katharina F Bullok · Christoph Sippel · Ingo G.H. Schmidt-Wolf
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    ABSTRACT: Immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide and pomalidomide, represent the basic principle of multiple myeloma treatment. However, the development of resistance is a limiting factor. Over the last years, the efficient application of cytokine-induced killer (CIK) cells has been reported as an alternative strategy to treat hematological neoplasms. In this study, we tested for a potential synergistic effect by combining the IMiDs thalidomide, lenalidomide and pomalidomide with CIK cells in different myeloma cell lines in vitro. Myeloma cells tested with CIK cells were significantly reduced. In the combination, myeloma cells were significantly reduced compared with cells only tested with IMiDs but not to the cells tested with CIK cells. Otherwise, the number of CIK cells was significantly reduced when treated with IMiDs. Because IMiDs are active in patients with myeloma, these results lead to the expectation that combination of IMiDs and CIK cells achieve better results in the treatment of multiple myeloma compared with the single use of IMiDs. Therefore, further examinations in an in vivo setting are necessary to have a closer look on the cellular interactions. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Hematological Oncology 03/2015; DOI:10.1002/hon.2200 · 3.08 Impact Factor
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    ABSTRACT: Novel agents such as lenalidomide and bortezomib have significantly improved today's therapy of multiple myeloma. Despite recent innovations, new therapeutic options are needed. The Wingless-related integration site (WNT) pathway is aberrantly activated in lymphoma and myeloma and therefore renders WNT signaling molecules attractive for the development of targeted therapies. Flunarizine was used in this study as it has chemical features similar to those of other known WNT inhibitors and already proven proapoptotic properties in leukemia cells. The antitumor apoptotic effect of flunarizine at doses ranging from 0.1-200 μM was investigated on three human lymphoma cell lines, one murine and four human myeloma cell lines by 3'3-Dihexyloxacarbocyanine iodide and propidium iodide staining in flow cytometry. Flunarizine induced significant apoptotic activity in all tested myeloma and lymphoma cell lines in a dose-dependent manner. Our results reveal a significant selective induction of apoptosis by flunarizine and suggest an in vivo effect against lymphoma and myeloma. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 03/2015; 35(3):1369-76. · 1.83 Impact Factor
  • Alexander Isaak · Stefan Hauser · Sebastian Rogenhofer · Ingo G H Schmidt-Wolf
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    ABSTRACT: Although targeted-therapy (TT) for patients with metastatic renal cell cancer (mRCC) has shown an improved outcome, their prognosis is still very poor. Immunotherapy with dendritic cells (DC) as one promising new treatment tries to fight cancer by boosting the patient's own immune system. The present analysis matches two different methods of treatment against mRCC, namely sequential TT versus DC vaccine therapy, by comparison of long-term overall survival (OS). Data of patients treated with DC vaccines (N=30) in three clinical phase I/II trials (1999-2003) and patients treated with clinical standard targeted-therapy (N=30) at the University Hospital of Bonn (2010-2013) were analyzed regarding their OS, as well as specific characteristics such as number and localization of metastatic sites. The mean OS from the first treatment was significantly higher in the TT than in the DC group (48 versus 21 months, range=3-85 months versus 1-57 months, respectively; p=0.0002). Patients with one (p=0.036) or two metastases (p=0.037) and especially patients with bone metastases (52 versus 12 months; p<0.0001) benefited significantly from TT. However, there was no significant difference between therapy types in patients with lung (p=0.147) or liver (p=0.745) metastases, or in patients with more than two metastatic sites (p=0.074). Targeted therapy is an effective treatment against mRCC, but is limited due to common adverse events and a higher toxicity when combinations of different-targeted agents are used. Immunotherapy with DC vaccines seems to be a potent and well-tolerated therapy against mRCC, possibly showing higher benefit for patients with specific sites of metastasis, and should be investigated as a co-treatment with TT in further studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 03/2015; 35(3):1575-82. · 1.83 Impact Factor
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    ABSTRACT: Multiple myeloma, a well-known but still incurable disease, is a hematological malignancy of B-lymphocytes. While standard chemotherapy regimens have been used for years, novel agents, such as lenalidomide and bortezomib, have become an essential part of today's therapies. Nevertheless, new therapeutical strategies are required in the future. Aberrant activation of wingless-related integration site (WNT)/β-catenin signaling promotes the development of several types of cancer. Recently, it has been demonstrated that the WNT pathway is also activated in lymphoma and myeloma. Thus, the WNT signaling molecules are attractive candidates for the development of targeted therapies. To this extent, we recently confirmed that the diuretic agent ethacrynic acid (EA) and the antifungal agent ciclopirox olamine (CIC) inhibit WNT signaling. Cinnarizine has similar chemical features to those of CIC. Thus, in this study the antitumor effect of cinnarizine on myeloma and lymphoma cells was investigated by DiOC6 and propidium iodide (PI)-staining in flow cytometry. Cinnarizine triggered a significant apoptotic activity in all tested myeloma and lymphoma cell lines in a concentration-dependent manner. Interestingly, healthy cells were mainly unaffected. These results reveal a significant selective induction of apoptosis by cinnarizine that might result from an inhibition of WNT signaling and suggest an in vivo efficacy against lymphoma and myeloma. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 02/2015; 35(2):835-41. · 1.83 Impact Factor
  • Zeitschrift für Gastroenterologie 01/2015; 53(01). DOI:10.1055/s-0034-1397166 · 1.05 Impact Factor
  • J Waysczak · A Vogt · I Schmidt-Wolf · CP Strassburg · MA Gonzalez-Carmona
    Zeitschrift für Gastroenterologie 01/2015; 53(01). DOI:10.1055/s-0034-1397181 · 1.05 Impact Factor
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    ABSTRACT: Aberrant activation of Wnt/β-catenin signaling promotes development and progression of various malignant neoplasms. Recent studies observed that the Wnt pathway is constitutively active in myeloma cells and promotes an exaggerated proliferation. Thus, the Wnt signaling pathway might be an attractive therapeutic target for multiple myeloma. In this study, we identified piceatannol as an inhibitor of the Wnt/β-catenin pathway and as a potent inducer of apoptosis in myeloma cells. Interestingly, healthy cells remained mainly unaffected. These results reveal a significant selective induction of apoptosis by piceatannol and suggest a significant in vivo effect against multiple myeloma. Copyright © 2014 John Wiley & Sons, Ltd.
    Hematological Oncology 12/2014; 32(4). DOI:10.1002/hon.2122 · 3.08 Impact Factor
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    ABSTRACT: Cytokine-induced killer (CIK) cells represent an exceptional T cell population uniting a T cell and natural killer cell like phenotype in their terminally differentiated CD3(+)CD56(+) subset, which features non-MHC-restricted tumor-killing activity. CIK cells are expandable from peripheral blood mononuclear cells and mature following the addition of certain cytokines. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures. Therefore, we established the international registry on CIK cells in order to collect and evaluate data about clinical trials using CIK cells for the treatment of cancer patients. Moreover, our registry is expected to set new standards on the reporting of results from clinical trials using CIK cells. Clinical responses, overall survival (OS), adverse reactions and immunologic effects were analyzed in 45 studies present in our database. These studies investigated 22 different tumor entities altogether enrolling 2,729 patients. A mean response rate of 39 % and significantly increased OS, accompanied by an improved quality of life, were reported. Interestingly, side effects of CIK cell treatment were minor. Mild fevers, chills, headache and fatigue were, however, seen regularly after CIK cell infusion. Moreover, CIK cells revealed numerous immunologic effects such as changes in T cell subsets, tumor markers, cytokine secretion and HBV viral load. Due to their easy availability and potent antitumor activity, CIK cells emerged as a promising immunotherapy approach in oncology and may gain major importance on the prognosis of cancer.
    Journal of Cancer Research and Clinical Oncology 11/2014; 141(5). DOI:10.1007/s00432-014-1864-3 · 3.08 Impact Factor
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    ABSTRACT: This largest prospective multicenter trial for adult patients with Burkitt lymphoma/leukemia aimed to prove efficacy and feasibility of a short-intensive chemotherapy combined with the anti-CD20 antibody Rituximab. 363 patients 16 to 85 years old (median 42 yrs) were recruited in 98 centers from 8/2002 until 06/2011. Treatment consisted of 6 five-day chemotherapy cycles with high-dose methotrexate, high-dose cytosine arabinoside, cyclophosphamide, etoposide, ifosphamide, corticosteroids, and triple intrathecal therapy. Patients >55 years received a reduced regimen. Rituximab was given d -1 before each cycle and twice as maintenance, for a total of 8 doses. The complete remission rate was 88% (319/363), the overall survival (OS) at 5 years 80%, and the progression-free survival (PFS) 71%, with significant difference between adolescents (≥15-25 yrs), adults (26-55 yrs) and elderly (>55 yrs) patients with an OS of 90%, 84%, and 62%. Full treatment could be applied in 86% of the patients. Most important prognostic factors were IPI (0-2 vs. 3-5, p=0.0005), aaIPI (0-1 vs. 2-3, p=0.0001), and gender (male vs. female, p=0.004). The high cure rate in this prospective trial with a substantial number of participating hospitals demonstrates the efficacy and feasibility of chemoimmunotherapy, also in elderly patients. The study is registered to as NCT00199082.
    Blood 10/2014; 124(26). DOI:10.1182/blood-2014-03-563627 · 10.45 Impact Factor

Publication Stats

10k Citations
1,351.11 Total Impact Points


  • 2014–2015
    • Centrum für Integrierte Onkologie
      Köln, North Rhine-Westphalia, Germany
  • 1999–2015
    • University of Bonn
      • • Institute of Pathology
      • • Department of Neurobiology
      • • Medizinische Klinik und Poliklinik I
      Bonn, North Rhine-Westphalia, Germany
  • 1999–2014
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
  • 2011
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2010
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2004–2007
    • University of Cologne
      • Department of Neurology
      Köln, North Rhine-Westphalia, Germany
  • 2001
    • Sigmund-Freud-Institut
      Frankfurt, Hesse, Germany
  • 1996–2000
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1993–1995
    • Freie Universität Berlin
      • Department of Hematology
      Berlín, Berlin, Germany
    • Stanford Medicine
      • Department of Medicine
      Stanford, CA, United States
  • 1990–1995
    • Stanford University
      • Division of Hematology
      Palo Alto, California, United States