memo - Magazine of European Medical Oncology

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0132-8

Dworzak, Michael

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0111-0

Willenbacher, W.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0119-5

Zielinski, Christoph; Brodowicz, Thomas

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0122-x

Kager, Leo

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0110-1

With current therapy more than 80% of children with acute lymphoblastic leukaemia (ALL) can be cured in industrialized countries. However, ALL is still amongst the leading causes of death from disease in children aged 1–15 years. Of note, antileukaemic medications can cause significant adverse drug reactions; and some patients have leukaemia cell clones that are resistant to current antileukaemic treatment. Therefore, further improvement of childhood ALL therapy is urgently needed. Pharmacogenomics aims to elucidate functionally relevant genomic determinants for drug disposition and response to improve drug therapy based on a patient’s genomic profile. Results from recent pharmacogenomic investigations including large-scale genome-wide analyses hold promise to improve ALL therapy in the near future.

Breuer, Sabine

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0109-7

The report summarizes several lectures that proved particularly notable for paediatric haematologists at the ASH meeting 2008. Neal S. Young (NIH, Bethesda, U.S.A.) illustrated his findings about the frequent impact of telomere shortening caused by mutations in the telomerase complex in the pathogenesis of severe aplastic anaemia (SAA). The presence of these mutations also has therapeutic implications, as carriers are at risk to respond poorly to immunosuppressive treatment regimens. The relevance of genome wide analysis of DNA copy number alterations (CNA) for the risk stratification in paediatric B-precursor ALL was demonstrated by Charles G. Mullighan (St. Judes Hospital, Memphis, U.S.A.). Mutations occurring in a number of genes that regulate lymphoid development (like IKZF-1) were identified as predictors of poor outcome. Furthermore, the evaluation of CNA in diagnostic and relapse samples of ALL patients allows to retrace the clonal evolution of the disease. Lyndal Kearney (Institute of Cancer Research, London, U.K.) reported on new insights into leukaemogenesis gained by comparing several identical twin-pairs with concordant TEL-AML1 positive B-precursor ALL. The results of single nucleotide polymorphism (SNP) arrays illustrate how pre-leukaemic, TEL-AML1 positive clones convert into overt ALL by acquiring secondary functional mutations. Defective apoptosis accounts for abnormal lymphocyte survival and autoimmune processes in autoimmune lymphoproliferative disease (ALPS). Stephan Grupp and David T. Teachey (Children’s Hospital, Philadelphia, U.S.A.) successfully applied the signal transduction inhibitor rapamycin to induce lymphocyte apoptosis in ALPS patients. Considerable clinical improvements were achieved in each of the patients treated in a phase I/II trial.

Kayser, S.; Schlenk, Richard

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0108-8

Gökbuget, Nicola; Wassmann, B.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0115-9

In this review we describe general therapeutic options for adult patients with acute lymphoblastic leukaemia and focus on specific new treatment strategies. Current novel approaches include monoclonal antibodies against leukaemic-associated antigens, new formulations of existing chemotherapeutic agents, new antimetabolites and nucleoside analogons and targeted molecular therapy. Some of these agents have already been adopted into standard regimens, leading to dramatically improved outcomes for example in mature B-ALL and in the formerly most unfavourable subgroup Philadelphia chromosome (Ph)/BCR-ABL-positive ALL, while others still remain in early phases of development.

Webersinke, G.; Rumpold, Holger

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0120-z

Myeloproliferative diseases (MPD) are characterized by the clonal expansion of mature myeloid cells. A reciprocal translocation between chromosome 9 and 22 is responsible for chronic myeloid leukaemia but not for the so-called Philadelphia Chromosome/BCR-ABL-negative MPDs. With the detection of mutations in the gene of the Janus kinase 2 (JAK2) in 2005, a specific genetic aberration was also found in BCR-ABL-negative MPD samples. These mutations lead to a constitutive activation of JAK2, which results in unlimited growth of haematopoietic precursor cells. Nowadays it is known that these mutations can be found at different frequencies in primary myelofibrosis, polycythemia vera and essential thrombocythemia. The precise role of the JAK2 mutations, however, in the pathogenesis of these diseases is not fully understood and some theories will be discussed. For the treatment of BCR-ABL-negative MPDs the inhibition of the hyperactive JAK2 seems to be promising. Several phase I and II studies investigating the effect of JAK-inhibitors are currently ongoing. In some preliminary data it has been shown that they effectivly reduce spleen size, leucocyte count and lead to a gain of body weight and a relief of constitutional symptoms. However, these results are preliminary, patient numbers are small, many data on other myelofibrosis-associated parameters are not evaluated yet and most of the patients in these clinical trials suffered from myelofibrosis. Although these preliminary data are promising, the effect in PV and ET as well as the long-term effect of these novel kinase inhibitors has to be reevaluated in the future.

Kassam, S.; Montoto, Silvia

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0123-9

Although the outcome of patients with non-Hodgkin lymphoma (NHL) has, in general, improved significantly over years, treatment failure due to drug resistance remains a problem. Recently, the focus of drug development has shifted from conventional cytotoxic drugs to agents directed against specific molecular targets and immunotherapy. This has mainly been driven by advances in the understanding of the molecular pathogenesis of NHL. A large number of promising new agents are in preclinical and clinical development. The challenge for clinicians is how best to incorporate them into already existing treatment regimes. This review will highlight some recent clinical trials focussing on targeted small molecules and monoclonal antibodies in NHL.

Willenbacher, W.; Willenbacher, E.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0107-9

Although hundreds of presentations, posters and abstracts dealt with any imaginable aspect of lymphomagenesis, diagnosis and treatment at the ASH 2008 meeting held in San Francisco from December 6–9, most experts in the field this year missed “the big thing”. But although no ground-shaking breakthroughs (to use a California style expression) in the field of NHL or Hodgkins lymphoma were presented, there were still many interesting scientific contributions made that will be covered in this strictly subjective selection.

Steurer, Michael

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0116-8

The dominating clinical presentations concerning CLL at this year’s ASH meeting were given on the results of two large randomized phase III trials exploring the use of rituximab (R) in addition to fludarabine and cyclophosphamide (FC). The data of these trials as well as a phase II trial applying R-Bendamustin convincingly demonstrated the clinical benefit of chemoimmunotherapy in CLL, at least for the younger and physically fit patients without del17p.

Nachbaur, David

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0117-7

Acute myeloid leukaemia (AML) is a genetically pleiomorphic disease. During recent years therapeutic and diagnostic developments have shifted the paradigm of “one size fits all” treatment to more targeted and personalized therapeutic strategies. Gene mutations and expression abormalities as well as minimal residual disease monitoring may exert profound effects on therapeutic and clinical decision making. In stem cell transplantation open questions remain on the long-term outcome of peripheral blood versus bone marrow stem cell transplantation as well as of reduced-intensity conditioning protocols. This article highlights the recent developments in both fields, AML and clinical transplantation, presented at the 2008 ASH meeting in San Francisco.

Stauder, Reinhard

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0118-6

Respective to MDS ASH 2008 focussed on individual clinical tailoring of treatment by wider adoption of comorbidity and prognostic scores. Concerning new agents, encouraging data on demethylating agents, as well as first clinical studies on new compounds like histon-deacetylase inhibitors (HiDACs) and clofarabin were presented.

Mlineritsch, Brigitte

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0114-x

Endocrine treatment in combination with signal transduction inhibitors was a major concern of this year’s San Antonio Breast Cancer Symposium. Johnston gave the first plenary lecture on how to overcome endocrine resistance. He presented the first results of the EGF30008 trial: Lapatinib in combination with letrozole. The efficacy of aromatase inhibitors compared with tamoxifen for the treatment of hormone receptor-positive breast cancer has been the subject of numerous large-scale clinical trials. Henning Mouridsen from Denmark presented new results from the BIG-1-98 trial. Raimund Jakesz and M Goetz on behalf of the ABCSG presented the results of the ABCSG trials 8 and the pharmacogenetic and gene expression profiles and molecular grade index for the prediction of endocrine therapy.

Sun, W.; Hutarew, G.; Gradl, J.; Gratzl, M.; Heumader, E.; Denz, H.; Fiegl, Michael

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0113-y

Effective systemic therapy for advanced pseudomyxoma peritonei (PMP) is the focus of investigation. We describe a case of PMP arising from an adenoma of the appendix in a 58-year-old man. First, the patient underwent explorative laparotomy with ileocoecal resection, but without possibility of major tumour debulking due to adhesive gross tumour masses. Subsequently, six cycles of Folfox IV chemotherapy were administered, without response, but with severe side effects. Upon progressive disease, a combination of bevacizumab and capecitabine led to a long-term stabilization of disease and obvious improvement of performance status. Our case suggests that modulation of tumour microenvironment and angiogenesis by bevacizumab, potentially augmented by monochemotherapy, may be beneficial in borderline tumours such as pseudomyxoma peritonei.