Showing papers by "Lorenz Trümper published in 2007"
TL;DR: A large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) offers new insights into the prognostic significance of rare chromosomal abnormalities and specific karyotypic combinations in MDS.
718 citations
TL;DR: A SNP within a distal enhancer that is associated with a subtype of leukemia and exerts a deleterious effect through remote transcriptional dysregulation in specific progenitor subtypes is identified.
Abstract: Targeted disruption of a highly conserved distal enhancer reduces expression of the PU.1 transcription factor by 80% and leads to acute myeloid leukemia (AML) with frequent cytogenetic aberrations in mice. Here we identify a SNP within this element in humans that is more frequent in AML with a complex karyotype, leads to decreased enhancer activity, and reduces PU.1 expression in myeloid progenitors in a development-dependent manner. This SNP inhibits binding of the chromatin-remodeling transcriptional regulator special AT-rich sequence binding protein 1 (SATB1). Overexpression of SATB1 increased PU.1 expression, and siRNA inhibition of SATB1 downregulated PU.1 expression. Targeted disruption of the distal enhancer led to a loss of regulation of PU.1 by SATB1. Interestingly, disruption of SATB1 in mice led to a selective decrease of PU.1 RNA in specific progenitor types (granulocyte-macrophage and megakaryocyte-erythrocyte progenitors) and a similar effect was observed in AML samples harboring this SNP. Thus we have identified a SNP within a distal enhancer that is associated with a subtype of leukemia and exerts a deleterious effect through remote transcriptional dysregulation in specific progenitor subtypes.
123 citations
TL;DR: The risk for leukocytopenia was associated with infections, antibiotic use, hospitalization and treatment-related mortality, indicating the clinical usefulness of the models, and a Web-based tool is made available to easily predict the hematotoxicity in clinical practice.
40 citations
TL;DR: Current study concepts evaluate the role of RIT consolidation in combination with antibody maintenance to achieve a potentially curative approach even in patients with advanced stage disease.
Abstract: Radioimmunotherapy (RIT) was approved for the treatment of relapsed or refractory CD20-positive follicular lymphoma (FL), subsequent to rituximab containing primary therapy. However, an increasing number of clinical studies have suggested that RIT may be more efficacious in an earlier phase of the disease. Therefore, a consensus meeting was held in May 2005 to define the optimal setting of RIT in the therapeutic algorithm of patients with advanced stage of FL. RIT is an established therapeutic option in relapsed FL. According to the reviewed data, RIT should be preferably used as consolidation after initial tumor debulking. First-line RIT may be applied in patients not appropriate for chemotherapy induction. Current study concepts evaluate the role of RIT consolidation in combination with antibody maintenance to achieve a potentially curative approach even in patients with advanced stage disease.
37 citations
TL;DR: In this paper, the pharmacokinetics of intravenous intravenous melphalan were analyzed in 64 patients after first administration of the drug and side effects were documented according to WHO criteria.
Abstract: Objectives Melphalan is widely used in the treatment of multiple myeloma. Pharmacokinetics of this alkylating drug shows high inter-individual variability. As melphalan is a phenylalanine derivative, the pharmacokinetic variability may be determined by genetic polymorphisms in the L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8). Methods Pharmacokinetics were analysed in 64 patients after first administration of intravenous melphalan. Severity of side effects was documented according to WHO criteria. Genomic DNA was analysed for polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron-exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were analysed by single nucleotide primer extension. Results Melphalan pharmacokinetics was highly variable with up to 6.2-fold differences in total clearance. A total of 44 polymorphisms were identified in LAT1 and 21 polymorphisms in LAT2. From all variants, only five were in the coding region and only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2. Numerous polymorphisms were found in the LAT1 and LAT2 5′-flanking regions but did not correlate with expression of the respective genes. No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects. Conclusions The study confirmed that these transporter genes are highly conserved, particularly in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan.
36 citations
TL;DR: The identified SVN10 epitope can be used to study the role of CD4+ TH and Treg cells in immune responses and possibly be included in a multivalent peptide vaccine against survivin.
33 citations
TL;DR: This study established the IL-10 genotypes in patients from the NHL-B1/ B2 studies from the German High-Grade Non-Hodgkin's Lymphoma Study Group and found no difference in OS or event-free survival between patients with IL- 10–1087AA and the other genotypes.
Abstract: The interleukin-10 gene promoter polymorphism −1087AG does not correlate with clinical outcome in non-Hodgkin's lymphoma
24 citations
TL;DR: Initial therapy with MCP significantly impairs the ability to collect stem cells and should be avoided for first line therapy of younger patients potentially qualifying for high dose consolidation and ASCT in first remission.
15 citations
TL;DR: Zevalin is a commercially available variation of the murine anti‐CD20 antibody ibritumomab coupled to Yttrium 90 via the tiuxetan chelator as well as the results of the pivotal studies and clinical strategies to implement this treatment into the routine practice of lymphoma oncology are presented.
Abstract: Targeted immunotherapy utilizing monoclonal antibodies has improved survival in both indolent and aggressive lymphoma significantly. Since malignant lymphomas are also responsive to radiation, the combination of targeted immunotherapy and radiation with radionuclide coupled to monoclonal antibodies is an attractive option to further improve treatment results. Zevalin is a commercially available variation of the murine anti-CD20 antibody ibritumomab coupled to Yttrium 90 via the tiuxetan chelator. The development of this novel drug as well as the results of the pivotal studies and clinical strategies to implement this treatment into the routine practice of lymphoma oncology are presented in this review.
11 citations
TL;DR: Clinical outcome of cytogenetic and blast count subgroups in a large cohort of 1440 patients with MDS suggests an equal prognostic significance of poor-risk cytogenetics compared with highly elevated BM blasts and suggests a higher score for unfavorable karyotypes in future integrative prognostic systems in MDS.
7 citations
TL;DR: The irradiation-based regimen was associated with more pulmonary and GI toxicity when compared to HD Mel, and subjects achieving CR may be more likely to enjoy prolonged DFS after TMI/Bu/Cy.
TL;DR: In this article, a 53-year-rige Patientin stellte sich mit akuten Schmerzen im rechten Bein, Kribbelparasthesien des rechte Fuses, ausgepragter Leukozytose (162 × 103/μl) sowie Anamie und Thrombozytopenie vor.
Abstract: Leukamische Embolien bei akuter (AML) und chronischer myeloischer Leukamie (CML) sind in der Regel mit einer Hyperleukozytose (Leukozyten > 100 000/μl) assoziiert und werden in vielen Fallen erst im Rahmen einer Autopsie gefunden. Die Hauptlokalisation fur Embolien sind die kleinen und mittleren Gefase von Lunge und Gehirn, selten sind die Herzhohlen betroffen. Eine Raritat sind arterielle Verschlusse der grosen Extremitatenarterien. Eine 53-jahrige Patientin stellte sich mit akuten Schmerzen im rechten Bein, Kribbelparasthesien des rechten Fuses, ausgepragter Leukozytose (162 × 103/μl) sowie Anamie und Thrombozytopenie vor. In der Anamnese lagen ein Leistungsknick mit deutlicher Verminderung der korperlichen Belastbarkeit seit etwa 4 Wochen und rezidivierende Infekte vor. Ursache der Beschwerden war ein akuter Verschluss der rechten A. femoralis communis und A. femoralis superficialis durch einen weisen Thrombus im Rahmen einer De-novo-AML (FAB M1/WHO: AML ohne Ausreifung) mit Leukostase bei Hyperleukozytose. Der Verschluss einer grosen Arterie durch einen leukamischen Embolus ist eine ungewohnliche Erstmanifestation einer AML. Leukamische Embolien in kleinen und mittleren Gefasen von Gehirn und Lunge sind hingegen haufiger. Leukamische Emboli treten typischerweise bei AML und CML in der Blastenkrise auf und sind viel seltener bei akuter (ALL) und chronischer lymphatischer Leukamie (CLL) zu finden. Ursachen fur solche Emboli sind sowohl eine Hyperleukozytose als auch die Expression von Adhasionsmolekulen, die die Interaktion zwischen den Blasten und dem Gefasendothel vermitteln. Therapeutische Optionen sind, neben dem sofortigen Beginn einer Vorphasenchemotherapie, die Leukapherese bzw. die Embolektomie beim Verschluss groser Gefase.