Ingo G H Schmidt-Wolf

Universitätsspital Basel, Bâle, Basel-City, Switzerland

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Publications (248)1093.54 Total impact

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    Beate Lauter · Ingo G H Schmidt-Wolf
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    ABSTRACT: Here, we studied 83 unselected multiple myeloma patients from December 2007 through December 2014. Lower 25(OH) D levels (<10 ng/mL) were associated with higher number of plasma cells in the bone marrow. Supplementation of vitamin D was accompanied with a significant increase in hemoglobin (11.8 to 12.3 p = .039), leukocyte (4.9 to 5.8 p = .011), and erythrocyte (3.8 to 4.0 p = .004) levels, while thrombocytes (200.5 to 175.2 p = .036) decreased. In conclusion, the present study found a high incidence of vitamin D deficiency and insufficiency in MM patients. In myeloma patients, vitamin D levels and supplementation should be more widely taken into account.
    Preview · Article · Oct 2015 · Cancer Investigation
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    ABSTRACT: Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary endpoint was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 [95% CI: 0.69-0.82] vs 0.69 [95% CI: 0.61-0.76]), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared to patients with high (P<0.001) and non-high risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56 vs 39%; P=0.005) and free of drug treatment (56 vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.Leukemia accepted article preview online, 14 October 2015. doi:10.1038/leu.2015.281.
    No preview · Article · Oct 2015 · Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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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.
    No preview · Article · Jul 2015 · Journal of Cancer Research and Clinical Oncology
  • 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.
    No preview · Article · Apr 2015 · DMW - Deutsche Medizinische Wochenschrift
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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.
    No preview · Article · Apr 2015 · Blood
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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.
    Full-text · Article · Apr 2015 · Haematologica
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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.
    No preview · Article · Mar 2015 · Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
  • 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.
    No preview · Article · Mar 2015 · Hematological Oncology
  • 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.
    No preview · Article · Mar 2015 · Anticancer research
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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.
    No preview · Article · Mar 2015 · Anticancer research
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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.
    No preview · Article · Feb 2015 · Anticancer research
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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.
    No preview · Article · Dec 2014 · Hematological Oncology
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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.
    No preview · Article · Nov 2014 · Journal of Cancer Research and Clinical Oncology
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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.
    Full-text · Article · Oct 2014 · Blood
  • I G H Schmidt-Wolf · C Straka · C Scheid · H Einsele · H Goldschmidt · M Engelhardt
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    ABSTRACT: Unlabelled: Multiple myeloma (MM) is with an incidence of 4-6/100 000 inhabitants a fairly frequent malignancy of B cells. The incidence increases markedly with age. In this review changes in the treatment of relapsed / refractory myeloma during the last decade have been analysed. The present standard of care in the progressive or refractory myeloma was elaborated by the working group "Refractory Multiple Myeloma" using an extensive literature search for studies published between 2003 and 2013. Outside of clinical trials, high-dose therapy with stem cell transplantation is recommended in fit patients up to 75 years without significant comorbidities. Ongoing studies address the question about the least toxic and the most effective treatment. Therefore, inclusion of patients in therapeutic trials and use of novel agent combinations is highly recommended, e.g. with 3(rd) generation-IMIDs (pomalidomide), new proteasome inhibitors, such as carfilzomib, ixazomib or oprozomib, antibodies, such as elotuzumab, daratumumab or SAR650984, siltuximab, tabalumab, denosumab, romosozumab, BTK-, HSP-inhibitors and other innovative phase I/II agents. Conclusion: Based on new insights in the pathogenesis of the disease, treatment options for MM have changed significantly in recent years. There is a significantly larger treatment diversity, i.e. more MM-active agents and combinations are available today. Even with relapsed MM, patients with the disease often live longer and have fewer complications.
    No preview · Article · Oct 2014 · DMW - Deutsche Medizinische Wochenschrift
  • Ilona Wall · Ingo G H Schmidt-Wolf
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    ABSTRACT: Background/aim: Activated Wnt signaling in cancer cells leads to cell proliferation. It has been shown that the Wnt pathway is activated in pancreatic adenocarcinoma cells. Therefore, we tested the effect of Wnt inhibitors in human and murine pancreatic cancer cell lines. Materials and methods: The Wnt inhibitors ethacrynic acid (EA), ciclopirox olamine (CIC), piroctone olamine (PO) and griseofulvin (GF) were tested in murine and human pancreatic cancer cell lines with the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: We showed that the Wnt inhibitors significantly reduced cell viability in murine, as well as human pancreatic cancer cell lines. Conclusion: These results may lead to a new therapeutic option with Wnt inhibitors for patients with pancreatic adenocarcinoma.
    No preview · Article · Oct 2014 · Anticancer research
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    ABSTRACT: Cytokine-induced killer (CIK) cells are a heterogeneous population of immune effector cells that feature a mixed T- and Natural killer (NK) cell-like phenotype in their terminally-differentiated CD3+CD56+ subset. The easy availability, high proliferation rate and widely major histocompatibility complex (MHC)-unrestricted antitumor activity of CIK cells contribute to their particularly advantageous profile, making them an attractive approach for adoptive immunotherapy. CIK cells have shown considerable cytotoxicity against both solid tumors and hematological malignancies in vitro and in animal studies. Recently, initial clinical experiences demonstrated the feasibility and efficacy of CIK cell immunotherapy in cancer patients, even at advanced disease stages. Likewise, the clinical application of CIK cells in combination with standard therapeutic procedures revealed synergistic antitumor effects. In this report, we will focus our consideration on CIK cells in the treatment of hematological malignancies. We will give insight into the latest advances and future perspectives and outline the most prominent results obtained in 17 clinical studies. Overall, CIK cells demonstrated a crucial impact on the treatment of patients with hematological malignancies, as evidenced by complete remissions, prolonged survival durations and improved quality of life. However, up to now, the optimal application schedule eventually favoring their integration into clinical practice has still to be developed.
    Full-text · Article · Aug 2014 · International Journal of Molecular Sciences
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    ABSTRACT: Background/aim: Advanced renal cancer still has a very poor prognosis. In this regard recent investigations demonstrated a constitutive activation of the Wnt signaling pathway in renal cell carcinoma (RCC) thereby promoting an exaggerated cell proliferation. Especially, β-catenin overactivation and the functional loss of endogenous Wnt antagonists are associated with RCC carcinogenesis and progression. Thus, influencing Wnt signaling might represent a promising target in RCC treatment. Materials and methods: It was recently confirmed that ethacrynic acid (EA), ciclopirox olamine (CIC) and piroctone olamine (PO) can inhibit Wnt signaling in various cancer cell lines. Herein we investigated their cytotoxic potential towards human RCC cells and their influence on the Wnt pathway concerning apoptosis as determined by 3,3'-dihexyloxacarbocyanine iodide (DiOC6) and propidium iodide (PI) staining in flow cytometry and immunoblotting. Results: All three agents, EA, CIC and PO triggered a significant apoptotic activity in tested RCC cell lines in a time- and concentration-dependent manner. Moreover, exposure to CIC and PO decreased the expression of β-catenin as the pivotal feature within the canonical Wnt pathway. However, β-catenin expression increased upon the treatment with EA. Conclusion: These results reveal a significant selective induction of apoptosis by EA, CIC and PO and suggest a suppression of RCC survival in part due to inhibition of Wnt/β-catenin signaling. The development of targeted-therapies affecting the Wnt signaling pathway might therefore lead to novel treatment options for RCC patients.
    No preview · Article · Aug 2014 · Anticancer research
  • H. Goldschmidt · M.-S. Raab · K. Neben · K. Weisel · I.G.H. Schmidt-Wolf
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    ABSTRACT: Hintergrund Das multiple Myelom ist eine maligne lymphoproliferative B-Zell-Erkrankung, die durch die Vermehrung von monoklonalen Plasmazellen gekennzeichnet ist. Ein Rezidiv tritt bei ca. 95 % der Patienten auf. Ziel Basierend auf der aktuellen Literatur soll eine Zusammenfassung der Therapieoptionen beim refraktären multiplen Myelom erarbeitet werden. Ergebnisse Beim rezidivierten und/oder refraktären multiplen Myelom (RRMM) haben „novel drugs“ wie Thalidomid, Bortezomib und Lenalidomid die Therapieergebnisse verbessert und zu einer Verlängerung des Gesamtüberlebens geführt. Die Hochdosistherapie, gefolgt von der autologen Blutstammzelltransplantation, ist auch im Rezidiv eine Therapieoption für „fitte“ Patienten (guter Allgemeinzustand) mit langer Remission (12 bis 24 Monate) nach erster Hochdosistherapie. Schlussfolgerung In die Wahl der Rezidivtherapie sind das Ergebnis und die Nebenwirkungen der Initialtherapie sowie patienten- und erkrankungsspezifische Faktoren einzubeziehen. Für refraktäre Patienten bzw. Patienten, die auf die Behandlung mit den etablierten neuen Medikamenten nicht ansprechen, sind mit Pomalidomid und Carfilzomib weitere Therapieoptionen in Deutschland gegeben. Neue Substanzen mit anderen Wirkprinzipien befinden sich beim RRMM in der klinischen Prüfung. Die allogene Transplantation mit hämatopoetischen Stammzellen ist in Studien weiter zu prüfen.
    No preview · Article · Mar 2014 · Der Onkologe
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    V Maevis · U Mey · G Schmidt-Wolf · I G H Schmidt-Wolf
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    ABSTRACT: Hairy cell leukemia (HCL) is part of the low-grade non-Hodgkin lymphoma family and represents approximately 2% of all leukemias. Treatment with splenectomy and interferon-α historically belonged to the first steps of therapeutic options, achieving partial responses/remissions (PR) in most cases with a median survival between 4 and 6 years in the 1980s. The introduction of the purine analogs (PA) pentostatin and cladribine made HCL a well-treatable disease: overall complete response rates (CRR) range from 76 to 98%, with a median disease-free survival (DFS) of 16 years a normal lifespan can be reached and HCL-related deaths are rare. However, insufficient response to PA with poorer prognosis and relapse rates of 30-40% after 5-10 years of follow-up may require alternative strategies. Minimal residual disease can be detected by additional examinations of bone marrow specimens after treatment with PA. The use of immunotherapeutic monoclonal antibodies (mAB) like rituximab as a single agent or in combination with a PA or more recently clinical trials with recombinant immunotoxins (RIT) show promising results to restrict these problems. Recently, the identification of the possible disease-defining BRAF V600E mutation may allow the development of new therapeutic targets.
    Preview · Article · Feb 2014 · Blood Cancer Journal

Publication Stats

11k Citations
1,093.54 Total Impact Points


  • 2015
    • Universitätsspital Basel
      • Klinik für Hämatologie
      Bâle, Basel-City, Switzerland
  • 2014-2015
    • Centrum für Integrierte Onkologie
      Köln, North Rhine-Westphalia, Germany
  • 1999-2015
    • University of Bonn
      • • Institute of Pathology
      • • Medizinische Klinik und Poliklinik I
      Bonn, North Rhine-Westphalia, Germany
  • 2001-2014
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
    • Sigmund-Freud-Institut
      Frankfurt, Hesse, Germany
  • 2004-2013
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
  • 2006
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 1996-1999
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1993-1995
    • Freie Universität Berlin
      • Department of Hematology
      Berlín, Berlin, Germany
  • 1990-1995
    • Stanford University
      • • Department of Medicine
      • • Division of Hematology
      Palo Alto, California, United States