Wolf-Dieter Ludwig

• M.D., Ph.D.
• Head of Department at HELIOS Klinikum Berlin-Buch

Humane Immunglobuline sind präformierte Antikörper zur Substitutionstherapie bei Immunmangelkrankheiten und zur Immunmodulation bei speziellen seltenen Krankheiten. Die Prävalenz dieser Erkrankungen kann nicht das über die GKV abgerechnete Verordnungsvolumen der Immunglobuline erklären. Der Umsatz insgesamt ist sogar höher, da es zusätzlich zum Apo...

Verordnungsprofil Das höchste Verordnungsvolumen unter den Onkologika haben weiterhin Hormonantagonisten zur Behandlung des Mammakarzinoms und des Prostatakarzinoms, auf die 63 % der definierten Tagesdosen (DDD) entfallen. An zweiter Stelle stehen inzwischen die monoklonalen Antikörper gefolgt von den klassischen Zytostatika mit der führenden Grupp...

Ausgabenprofil Die Arzneimittelnettoausgaben der Gesetzlichen Krankenversicherung (GKV) sind 2021 auf 50,3 Mrd. € gestiegen. Die Zunahme gegenüber 2020 übersteigt mit fast 9 % klar die Vorjahreszunahme. Bei GKV-Gesamtausgaben von ca. 263 Mrd. € stieg der Arzneimittelanteil auf fast 18 % der Leistungsausgaben der GKV. Wie seit Jahren stellen nach de...

Auf einen Blick Ausgabenprofil Die Arzneimittelausgaben der Gesetzlichen Krankenversicherung (GKV) mit Zuzahlungen der Versicherten (V) sind auch 2020 erneut um 5,1 % auf 45.579 Mrd. € (+2,216 Mrd. €, Konto 04399V) gegenüber dem Vorjahr angestiegen und liegen damit weiterhin bei 17,2 % der Leistungsausgaben der GKV (Bundesministerium für Gesundheit...

Auf einen Blick Verordnungsprofil Das höchste Verordnungsvolumen unter den Onkologika haben weiterhin Hormonantagonisten zur Behandlung des Mammakarzinoms und des Prostatakarzinoms, auf die 62 % der definierten Tagesdosen (DDD) entfallen. An zweiter Stelle stehen die klassischen Zytostatika mit der führenden Gruppe der Antimetabolite, was vor allem...

Auf einen Blick Verordnungsprofil Humane Immunglobuline sind präformierte Antikörper zur Substitutionstherapie bei Immunmangelkrankheiten und zur Immunmodulation bei speziellen seltenen Krankheiten. Die Verordnungen sind relativ niedrig, da die Versorgung weitgehend über Direktlieferverträge der Krankenkassen mit Krankenhäusern und Spezialambulanze...

Der Arzneiverordnungs-Report ist seit 1985 eine gemeinsame Publikation von Autoren aus Pharmakologie, Klinik, Praxis, Gesundheitsökonomie und Krankenversicherung. Basis sind die Verordnungsdaten von Arzneimitteln für ambulante Patienten der gesetzlichen Krankenversicherung (GKV). Datenbasis des Jahres 2020 sind ca. 820 Mio. Verordnungen von 150.36...

Dose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = “dose-dense”) and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = “...

Purpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific...

Background: The intensive polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) is very active in patients with advanced-stage Hodgkin's lymphoma, albeit at the expense of severe toxicities. Individual patients might be cured with less burdensome therap...

Immunophenotyping by flow cytometry (FCM) is a worldwide mainstay in leukemia diagnostics. For concordant multicentric application, however, a gap exists between available classification systems, technologic standardization, and clinical needs. The AIEOP-BFM consortium induced an extensive standardization and validation effort between its nine nati...

Purpose: To evaluate the framework of drug information produced by public health and regulatory institutions in Europe. Materials and methods: We carried out a short survey asking editors of ISDB bulletins of the European region to indicate the main sources of drug information provided by public health and regulatory authorities in their countri...

Purpose: To investigate the prognostic impact of the coexpression of the natural killer cell marker CD56 / neural-cell adhesion molecule NCAM and to compare it to the immunophenotype subgroups according to the EGIL/WHO 2008 classification and to the early T-cell precursor (ETP) subtype for patients with T-ALL treated in the ALL-BFM 2000 protocol. P...

Purpose: To investigate the prognostic impact of the coexpression of the natural killer cell marker CD56 / neural-cell adhesion molecule NCAM and to compare it to the immunophenotype subgroups according to the EGIL/WHO 2008 classification and to the early T-cell precursor (ETP) subtype for patients with T-ALL treated in the ALL-BFM 2000 protocol. P...

Die durchflusszytometrische Immunphänotypisierung spielt eine wichtige Rolle in der hämatologisch-immunologischen Routinediagnostik, insbesondere bei der Lymphozytentypisierung sowie der Diagnostik und Verlaufsbeurteilung von benignen und malignen hämatologischen Erkrankungen. Die Möglichkeiten wie auch Limitationen der immunphänotypischen Diagnost...

We randomized 3375 adults with newly-diagnosed AML or high-risk myelodysplastic syndrome (MDS) to test whether increasingly-intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. 1529 subjects <60 years were randomized to receive: (1) a 1st course of induction therapy with high-dose cytarabine a...

Indications for metamizole in 161 spontaneous reports of suspected metamizole-induced agranulocytosis

In 1986, the risk of agranulocytosis prompted German authorities to restrict the indications for metamizole use. After an initial decline, prescriptions increased from <20 million defined daily doses in 1990 to >140 million in 2012. Concurrently, spontaneous reports of agranulocytosis increased from about 10 in 1990 to >50 in 2012. In this study, r...

Background Advances in basic science have greatly improved our understanding of the mechanisms driving tumor formation and growth, and have enabled the development of many new cancer drugs and drug-based treatment strategies. Simultaneously, the costs of drugs for treating cancer patients have risen considerably worldwide. This strong upward trend,...

Authors' conflicts of interest may affect the content of medical guidelines. In April 2010, the Association of Scientific Medical Societies in Germany (AWMF) issued recommendations on how such conflicts of interest should be dealt with. Most AWMF guidelines are so-called S1 guidelines developed by informal consensus in a group of experts. We now pr...

Minimal residual disease evaluation by multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal r...

Introduction: Immunochemotherapy has become the standard of care for patients with mantle-cell lymphoma (MCL) (Dreyling et al., ESMO recommendation for MCL, 2013). Previously, the German Low-Grade Lymphoma Study Group (GLSG) has shown in a randomized trial (GLSG2000) that the addition of rituximab to CHOP improves response rates in untreated advanc...

Technical advances in the field of genomic analyses have stimulated a large number of discovery studies on etiological and clinical endpoints in acute lymphoblastic leukemia (ALL) to provide new avenues for preventive strategies, diagnostics and treatment. Recently, deletion of IKZF1 (IKZF1del) was described as a poor prognostic factor in pediatric...

Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important informati...

Objectives To better understand the molecular pathogenesis of T-cell large granular lymphocyte leukemia (T-LGL) we decided to search for those genetic alterations in T-LGL patients and MOTN-1 cell line (established from T-LGL patient) that have an impact on gene expression and as a result can influence cell biology.MethodsmFISH analysis of the MOTN...

-

Background For curative treatment of younger patients with acute myeloid leukemia (AML) double induction with two cycles of intensive cytarabine/ anthracycline based chemotherapy 21 days apart is the current standard of care. In the prospective randomized AML-CG 2008 trial we asked question whether current results could be improved on by a dose-den...

The recommendations in clinical guidelines are based on clinical trial findings and expert opinion. The influence of drug companies on these two factors is illustrated with two examples. A judicially ordered expert review revealed that the market authorization holder (MAH) of gabapentin manipulated study data. Gabapentin was, therefore, chosen as a...

Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from an intensified treatment. We earlier identified PTPRC (CD45) gene expression as potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 wa...

Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%...

Background: Flow cytometry immunophenotyping (FCM) is an undispensable tool for the diagnosis and for the treatment stratification of childhood acute lymphoblastic leukemia. The correlation of the EGIL-classification with prognostically relevant parameters like age, prednisone response and risk group is analyzed. Patients: Between March 2000 and J...

The market authorisation or extension of indication for all oncology drugs in Europe is now based on Regulation (EC) No. 726/2004, a centralised procedure of the European Medicines Agency (EMA). Studies in recent years have highlighted deficiencies in pivotal studies. For example, the requirements of the EMA are not always consistently followed and...

Abstract Background: Despite improvements of treatment results for pediatric T-cell acute lymphoblastic leukemia (T-ALL), approximately 20% of patients relapse with dismal prognosis. Phosphatase and tensin homolog (PTEN) inactivation and NOTCH1 activation are known frequent leukemogenic events but their effect on outcome have been controversial. De...

Research over the past two decades has untangled the molecular heterogeneity of cancer at the cellular level. The molecular techniques that have been developed in the past 5 to 10 years are dramatically improving our understanding of the genomic aberrations that underlie the malignant transformation of normal cells. At the same time, however, advan...

Dear Editor,We would like to present a case with a parainfectious dropof factor XIII (FXIII) pointing to a so far not described linkbetween coagulation and infection. A 3-year-old girl wasadmitted to our clinic due to acute joint swelling and hae-matomas during an uncomplicated infection of the upperrespiratory tract lasting since 3 weeks. The chil...

IKZF1 gene deletions have been associated with a poor outcome in pediatric precursor B-cell acute lymphoblastic leukemia. To assess the prognostic relevance of IKZF1 deletions for patients treated on Berlin-Frankfurt-Munster Study Group trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia samples by Multiplex Ligation-Depende...

Novel immunosuppressive/modulating therapies with monoclonal antibodies (MABs) have been associated with progressive multifocal leukoencephalopathy (PML), a potentially fatal disease of the brain caused by the JC virus. Taking the complex diagnostic testing and heterogeneous clinical presentation of PML into account, an agreed case definition for P...

For confirmatory trials that are used by the European Medicines Agency (EMA) for approval or extension of approval for anticancer drugs, detailed guidelines have been described regarding, for example, the aims, patient selection, design and endpoints of the study. Several studies in recent years have shown insufficiencies in pivotal trials, for exa...

For confirmatory trials that are used by the European Medicines Agency (EMA) for approval or extension of approval for anticancer drugs, detailed guidelines have been described regarding, for example, the aims, patient selection, design and endpoints of the study. Several studies in recent years have shown insufficiencies in pivotal trials, for exa...

Background: Flow cytometric analysis of leukemia-associated immunophenotypes and polymerase chain reaction-based amplification of antigen-receptor genes rearrangements are reliable methods for monitoring minimal residual disease. The aim of this study was to compare the performances of these two methodologies in the detection of minimal residual d...

Ergebnisse der Grundlagenforschung haben in den vergangenen 2 Jahrzehnten die molekulare Heterogenität von Tumorerkrankungen aufgezeigt. Durch die Entwicklung neuer Technologien in den letzten 5 bis 10 Jahren war es möglich, eine Vielzahl von krebsauslösenden Veränderungen im Genom von Tumorzellen zu beschreiben, die letztlich zur malignen Transfor...

Quantification of minimal residual disease (MRD) by real-time PCR directed to TCR and Ig gene rearrangements allows a refined evaluation of response in acute lymphoblastic leukemia (ALL). The German Multicenter Study Group for Adult ALL prospectively evaluated molecular response after induction/consolidation chemotherapy according to standardized m...

Sunitinib and sorafenib can induce serious adverse drug reactions (ADR) such as hypothyroidism. However, the incidence has not been reliably determined in clinical trials. To determine incidence rates (IR) and hazard ratios (HR) of thyroid hormone (TH) therapy as a surrogate for sunitinib- and sorafenib-induced clinical hypothyroidism. A cohort stu...

Die Anwendung von zugelassenen Arzneimitteln außerhalb ihres Zulassungsstatus (Off-Label-Use) ist Bestandteil der Pharmakotherapie bei vielen Erkrankungen, insbesondere bei seltenen Erkrankungen und in Fällen von Therapieresistenz. Die nationalen Vorgaben, wie sie durch das Sozialgesetzbuch (SGB) V, die Urteile des Bundessozialgerichts, die Bewertu...

Research over the past two decades has untangled the molecular heterogeneity of cancer at the cellular level. The molecular techniques that have been developed in the past 5 to 10 years are dramatically improving our understanding of the genomic aberrations that underlie the malignant transformation of normal cells. At the same time, however, advan...

Various investigations have identified deficits in clinical studies conducted for the market authorisation of haematological and oncological drugs. Based on data from European Public Assessment Reports (EPAR) of the European Medicines Agency (EMA), an analysis of the quality of these studies, which serve as the basis of marketing authorisation of c...

752 Risk stratification in the childhood ALL-BFM clinical trial has been based on molecular/cytogenetic markers and the in vivo response to treatment (blast reduction in peripheral blood after prednisone prephase, bone marrow clearance after induction treatment and minimal residual disease (MRD) after induction and induction consolidation). These c...

1639 Introduction Maintenance using interferon-α (IFN) had previously been shown to be effective in indolent lymphoma (Solal-Celigny et al., NEJM 1993, Hagenbeek et al., JCO 1998). However, data on the impact of IFN in lymphoplasmacytic lymphoma (LPL) and after immuno-chemotherapy are rare. In two GLSG first-line trials which included LPL patients...

250 Survival of adult ALL has improved over the past decade to >50% with contemporary, risk adapted, targeted treatment strategies. However, published results of relapsed ALL are poor. In 4 retrospective studies with 1494 patients (pts) the CR rate after first salvage therapy was 40% and the long-term survival was only 6% including stem cell transp...

742 Further improvement of outcome in childhood acute lymphoblastic leukemia (ALL) could be achieved by identifying additional high-risk (HR) patients who then may benefit from an intensified treatment. In trial ALL-BFM 2000, the HR group was defined by inadequate initial response to induction treatment [poor prednisone response on treatment day ei...

740 Despite recent advances in treatment results of pediatric T-ALL, approximately 20% of the patients relapse and then have a dismal prognosis. Therefore, we aimed to identify molecular biomarkers that help in stratifying patients according to risk early in the course of treatment. We have analysed the clinical interaction of PTEN and NOTCH1 mutat...

2773 Introduction For patients with high-risk myelodysplastic syndromes an epigenetic therapy with hypomethylating agents is considered standard of care. Intensive chemotherapy can be offered to a subset of patients; however, data about the long-term outcome of MDS patients receiving intensive chemotherapy are scarce. Methods For this evaluation,...

The t(10;11)(p12;q14) is a recurring chromosomal translocation that gives rise to the CALM/AF10 fusion gene, which is found in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma. We analyzed the fusion transcripts in 20 new cases of CALM/AF10-positive leukemias, and compared the gene expression profile of 10 of these to 125...

Numerous reports have been published on the association between kinetics of leukemic cells during early treatment of childhood acute lymphoblastic leukemia and therapeutic outcome. In contrast, little is known about the prognostic relevance of normal blood counts in this setting. Normal hematopoiesis during and after induction treatment (days 8, 15...

The lymphocyte surface glycoprotein CD26 anchors adenosine deaminase to the lymphocyte surface and possesses dipeptidyl peptidase IV activity. A distinct subset of CD26++ lymphocytes in autologous hematopoietic progenitor cell transplants (HPCTs) was investigated with regard to clinical outcome after autologous HPCT. The phenotype of these cells wa...

In the clinical management of children with relapsed acute lymphoblastic leukemia (ALL), treatment resistance remains a major challenge. Alterations of the TP53 gene are frequently associated with resistance to chemotherapy, but their significance in relapsed childhood ALL has remained controversial because of small studies. Therefore, we systemati...

Direct-to-consumer advertising (DTCA) of prescription drugs has become a focus of public policy concern and academic research. Through it, pharmaceutical companies influence major parts of the health system, including the drug trials upon which DTCA is based. Advocates emphasize its potential in educating the public about health conditions and trea...

How eliminating “risk illiteracy” among doctors and patients will lead to better health care decision making. Contrary to popular opinion, one of the main problems in providing uniformly excellent health care is not lack of money but lack of knowledge—on the part of both doctors and patients. The studies in this book show that many doctors and most...

The features of 100 mixed-phenotype acute leukemias (MPALs), fulfilling WHO 2008 criteria, are documented. Myeloid and T-lineage features were demonstrated by cytoplasmic myeloperoxidase and CD3; B-lineage features were demonstrated by at least 2 B-lymphoid markers. There were 62 men and 38 women; 68% were adults. Morphology was consistent with acu...

ZusammenfassungMedikamentöse Therapieinnovationen in der Onkologie werfen medizinische und ethische Fragestellungen auf. Die zunehmende Inzidenz und Prävalenz von Krebserkrankungen sowie die Zulassung neuer, in aller Regel kostspieliger Wirkstoffe sind mit steigenden Gesamtkosten für die Behandlung von Krebserkrankungen verbunden. Deshalb ist die E...

Innovations in the drug treatment of cancer patients pose several medical and ethical challenges. The increasing incidence and prevalence of cancer, in combination with the availability of new and usually highly expensive anticancer drugs, are associated with a significant increase in the general costs for the treatment of cancer patients. Therefor...

Various investigations have identified deficits in clinical studies conducted for the market authorisation of haematological and oncological drugs. Based on data from European Public Assessment Reports (EPAR) of the European Medicines Agency (EMA), an analysis of the quality of these studies, which serve as the basis of marketing authorisation of c...

Publication bias describes the distortion of data in scientific journals resulting from the fact that studies with significant and positive results are more likely to be published than studies with negative or insignificant results. In studies funded by pharmaceutical companies publication bias has a considerable impact. It has been shown that more...

409 Alteration of the IKZF1 gene – encoding the transcription factor IKAROS, a key player in lymphoid development and tumor suppression – has been reported to be associated with a poor outcome in pediatric precursor B-cell ALL, especially in cases positive for the BCR-ABL1 fusion gene. In order to assess the prognostic value of IKZF1 deletions in a...

Die Produktion hämatopoetischer Zellen unterliegt einer engen Kontrolle durch auch als Zytokine agierende Wachstumsfaktoren. Granulozyten-Kolonie-stimulierender Faktor (G-CSF), Erythropoetin (EPO) und Erythropoese-stimulierende Wirkstoffe (ESA) sowie Thrombopoese-stimulierende Wirkstoffe (TSA) stehen für den klinischen Gebrauch zur Verfügung. G-CSF...