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Biomedical subjects

Roland Mertelsmann

Publications and source records attributed to Roland Mertelsmann.

8 recordsLinked to original sources
PubMed2006

The epitope recognized by rituximab.

Rituximab is a monoclonal antibody widely used in the treatment of malignant lymphoma and autoimmunity. Its epitope within the B-cell antigen CD20 is largely unknown. We used phage display libraries to select peptides binding to rituximab. Enriched peptides showed 2 sequence patterns: one motif (CALMIANSC) is related to (170)ANPS(173) within CD20, while another motif (WEWTI) may mimic the CD20 segment (182)YCYSI(185). Phages displaying either motif specifically bound rituximab. Binding to rituximab by the CD20 peptides ANPS and YCYSI was weak when used separately and enhanced when both peptides were linked. Recombinant CD20 extracellular loop proteins blocked binding of the selected CWWEWTIGC phage to rituximab, suggesting that CWWEWTIGC mimics the epitope. Blocking capacity was strongly reduced upon mutation of the CD20 strings ANPS or YCYSI. We conclude that rituximab binds a discontinuous epitope in CD20, comprised of (170)ANPS(173) and (182)YCYSI(185), with both strings brought in steric proximity by a disulfide bridge between C(167) and C(183).

Amino Acid Sequence↗
PubMed2006

Treatment decision-making for older patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: problems and approaches.

BACKGROUND AND OBJECTIVES: High-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are mainly diseases of patients over the age of 60 years. In these patients, intensive chemotherapy and/or allogeneic blood stem cell transplantation are the only curative treatment approaches, while non-curative options include low-dose chemotherapy or best supportive care alone. The basis for treatment decision-making in this clinically and biologically heterogeneous group is not well defined. DESIGN AND METHODS: In order to investigate treatment stratification patterns and outcomes in this population, we performed a systematic literature search in MedLine for relevant clinical reports published between 1989 and 2006. Only large population-based investigations and publications of clinical trials with more than 40 patients were analyzed. RESULTS: In 36 AML studies involving a total of 12,370 patients (median age 70 years) median overall survival approached 30 weeks for intensively treated patients. In patients receiving best supportive care alone, or best supportive care plus non-intensive treatment, median overall survival was 7.5 and 12 weeks, respectively. The complete remission rate after induction was 44%, and in those patients who achieved complete remission age no longer influenced prognosis. In 18 large studies approximately 50% of AML patients received induction therapy, 30% non-intensive chemotherapy and 20% supportive care only. INTERPRETATION AND CONCLUSIONS: Due to the scarcity of randomized AML/MDS trials in which older patients are assigned to either induction or less intense therapy, predictors to identify older patients most likely to benefit from intensive therapy and novel tools to optimize (or even standardize) recommendations are needed. We propose that in this patient population in the future, geriatric assessment instruments and comorbidity scoring are implemented in treatment decision-making.

Age Factors↗
PubMed2005

Imatinib mesylate as a novel treatment option for hypereosinophilic syndrome: two case reports and a comprehensive review of the literature.

Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Recent reports document the efficacy of imatinib mesylate in a large proportion of HES patients (65%). Rearrangements involving the platelet-derived growth factor receptor genes (PDGFRA and PDGFRB), both tyrosine kinase receptors, have been demonstrated to be pathogenetically linked to the dysregulated clonal overproduction of eosinophils. This refined hypothesis has been confirmed by the discovery of the novel FIP1L1-PDGFRA fusion gene, which is a gain-of-function gene on chromosome 4q12. Its product is an imatinib-sensitive tyrosine kinase, which can be found in a subset of patients with HES, particularly in those responding to treatment with imatinib mesylate. Here, we sum up recent knowledge of clinical features, pathophysiology and novel treatment aspects of HES by performing a comprehensive search of the available literature and report on 94 patients. We particularly address the issue of organ involvement and specific characteristics of the variable clinical pictures. In addition, two cases will be presented, which illustrate typical clinical scenarios and treatment outcome.

Adult↗
PubMed2004

Epidemiology of non-Hodgkin's lymphoma (NHL): trends, geographic distribution, and etiology.

While for most cancers incidence and mortality are decreasing, those of non-Hodgkin's lymphoma (NHL) are steadily increasing. Research to define reasons for this increase is extensive, but has not yet resolved them. We have conducted a literature analysis on trends regarding changes in the incidence, geographic distribution, and etiologic factors of NHL. From our own and previous analyses, an increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise of 1-2%, resulting in almost a doubling of the NHL incidence. This rise has been noted worldwide, particularly in elderly persons >55 years. Concerning gender subgroups, a male predominance throughout all age groups is apparent. Although the NHL incidence has historically been higher in whites than blacks, disproportional increases have recently been observed in the latter group. Increases in high-grade NHL and extranodal disease are predominant. Differences in geographic distribution are striking for follicular lymphoma, which is more common in Western countries than elsewhere. Asians have higher rates of aggressive NHL, T-cell lymphomas, and extranodal disease. In the Middle East, high rates of intestinal extranodal disease are observed, whereas in Africa, endemic Burkitt's lymphoma accounts for a substantial proportion. Risks for developing NHL include immunosuppression and a causal link between infectious agents, and lymphomagenesis has also been determined, particularly for human T-cell leukemia/lymphoma virus type 1 (HTLV-1), Epstein-Barr virus (EBV), and Helicobacter pylori infections. Exposure to environmental agents and occupational risks have been studied; however, their significance is as yet uncertain.

Environmental Exposure↗
PubMed2004

Hematopoietic stem cell transplantation: more than just hematopoietic?

A wealth of evidence has surfaced in the last three years to challenge age-old notions of stem cell compartments in mammalian adult tissues. It was only recently realised that large cellular infusions in clinical practice might contain stem cells with flexible fate potential. This review discusses the current status of the occurence of epithelial chimerism after hematopoietic cell transplantation and presents existing data on detection methodology, characteristics, underlying mechanisms, physiological implications and clinical significance.

Hematopoietic Stem Cell Transplantation↗