BackgroundViscum album L extracts (VAE, mistletoe) and isolated mistletoe lectins (ML) have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects.MethodsSystematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune parameters or infections or adverse drug reactions.Results69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases.ConclusionsApplication of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.

Hintergrund und Fragestellung: 2005 wurde ein «Health Technology Assessment»(HTA)-Bericht zu Wirksamkeit, Sicherheit, Wirtschaftlichkeit und Bedarf der Anthroposophischen Medizin (AM) erstellt. Im Kontext des «Schweizer Volksvotums pro Komplementärmedizin» (Mai 2009) erfolgte ein Update des HTA-Berichts. Design: Update des HTA-Berichts durch eine systematische Übersichtsarbeit. Methoden: Das Update wurde in Anlehnung an den bereits vorhandenen HTA-Bericht sowie entsprechend den Vorgaben des Schweizer Bundesamtes für Gesundheit durchgeführt. Nach klinischen Studien wurde systematisch in vier Datenbanken, in einer spezialisierten Zeitschrift und mit Hilfe umfassender Expertenkontakte gesucht. Studien wurden nach vorab definierten Kriterien ausgewählt, die Daten extrahiert und die Qualität individuell überprüft. Ergebnisse: 70 neue klinische Studien zur Wirksamkeit wurden gefunden. Damit liegen derzeit insgesamt 265 klinische Studien zur AM vor: 38 randomisierte Studien, 36 prospektive und 49 retrospektive, nichtrandomisierte, vergleichende Studien sowie 90 prospektive und 52 retrospektive Studien ohne Kontrollgruppe. Die Studien untersuchten ein weites Spektrum an AM-Therapien bei einer Vielzahl von Erkrankungen; das Gesamtsystem der AM untersuchten 38 Studien, in 10 Studien ging es um nichtpharmakologische Therapien, 133 befassten sich mit Misteltherapie bei Krebs und 84 untersuchten sonstige AM-Arzneitherapien. Die Studien zeigten in der Mehrzahl ein positives Ergebnis für AM. Die methodische Qualität der Studien variierte sehr; einige wiesen erhebliche Schwächen auf, andere waren sorgfältig durchgeführt. Die Praxisrelevanz war überwiegend hoch. Bei Beschränkung auf die qualitativ besseren Studien ergab sich ein positives Ergebnis für die AM. Nebenwirkungen und Risiken waren selten und im Schweregrad meist mild oder mäßig. Studien zur Sicherheit zeigten eine insgesamt gute Verträglichkeit. Schlussfolgerung: Studien unterschiedlichen Designs und unterschiedlicher Qualität beschreiben bei einer Vielzahl von Erkrankungen ein für die AM medizinisch gutes und für die Patienten zufriedenstellendes, sicheres und vermutlich auch kostengünstiges Behandlungsergebnis. Weiterführende qualitativ hochwertige Evaluationen sind wünschenswert.

Various treatment options exist for patients with chronic lymphocytic leukaemia (CLL). Clinical registries provide insight into routine treatment and identify changes in treatment over time. The Tumour Registry Lymphatic Neoplasms prospectively collects data on the treatment of patients with lymphoid B-cell neoplasm as administered by office-based haematologists in Germany. Data on patient and tumour characteristics, co-morbidities, systemic treatments, and outcome parameters are recorded. Eight hundred and six patients with CLL were recruited between May 2009 and August 2013. At the start of first-line treatment, median age was 71 years, 64% were male, and 44% had a Binet stage C disease. The most frequently used first-line/second-line regimens were bendamustine + rituximab (BR, 56%/55%), fludarabine + cyclophosphamide + rituximab (FCR, 22%/11%), and bendamustine (B, 5%/9%). Chlorambucil was used in only 7% (first-line) and 6% (second-line) of patients. Patients treated with FCR were younger and healthier than patients treated with BR. Overall, 91% of first-line treatments were successful (40% complete response). Real-life patient populations differ considerably from patients treated in randomized controlled trials. BR and FCR dominate the first-line and second-line treatments of CLL by office-based haematologists in Germany. Future analysis will investigate progression-free and overall survival times. © 2014 The Authors. Hematological Oncology Published by John Wiley & Sons, Ltd.

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SummaryBackground: Various treatment options exist for patients with multiple myeloma (MM). Clinical registries provide insight into routine treatment and identify changes in treatment over time. Patients and Methods: The Tumour Registry Lymphatic Neoplasms (TLN) prospectively collects data on the treatment of patients with lymphoid B cell neoplasms as administered by office-based haematologists in Germany. Data on patient and tumour characteristics, comorbidities, systemic treatments and outcome parameters are recorded. Results: 371 non-transplant patients with MM were recruited between 2009 and 2011. At the start of first-line (second-line) treatment, the median age was 73 (75) years; 67% (74%) of the patients had stage III MM (classification of Durie and Salmon) and 19% (28%) had renal insufficiency. In the first line, 40% of the patients received bortezomib + melphalan + prednisone (VMP), 25% received bortezomib ± dexamethasone (V±D) and 8% were treated with melphalan + prednisone + thalidomide (MPT). While use of bortezomib-based regimens increased from 67% (2009) to 85% (2011), use of melphalan-based regimens decreased from 68% to 48%. The overall objective response rate of treatment was 82%. In the second line, 34% of the patients received V±D and 16% lenalidomide + dexamethasone (LD). Conclusion: Bortezomib-based regimens dominate the first- and second-line treatment of MM. Future analyses will investigate outcome data, e.g. effectiveness of bortezomib retherapy compared to other second-line treatments.

The German version of BOMET-QoL-10 is a valid, reliable, brief, and clear instrument able to measure HRQoL in patients with BM.

Introduction Fludarabine, cyclophosphamide, rituximab (FCR) is currently considered the standard of care for medically fit patients (pts) with untreated chronic lymphocytic leukaemia (CLL). However, due to its significant haematological toxicity other, potentially less toxic regimens are currently under investigation. Results of the phase III trial CLL 10 of the German CLL-Study Group (GCLLSG) comparing FCR to bendamustine, rituximab (BR) are eagerly awaited. Since clinical trials are restricted to highly selected pts, we here investigated effectiveness of BR and FCR in unselected pts with CLL treated in routine practice by German office-based haematologists. Methods The open, longitudinal, multicentre, clinical registry on lymphoid neoplasms (TLN Registry, ClinicalTrial.gov registry NCT00889798) prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered by a network of German office-based haematologists. Pts are followed for 5 years. A broad set of data regarding patient and tumour characteristics, comorbidities, all systemic treatments and response rates, progression-free survival and overall survival are recorded. Automated plausibility and completeness checks with subsequently generated queries by the electronic data capture system ensure data reliability. In addition, data managers regularly check for plausibility and issue queries. Since May 2009, 111 sites have actively recruited a total of 2897 pts. Results 381 pts with CLL, recruited at the onset of their 1st-line therapy and treated with BR (69%) or FCR (31%), were included in this analysis. The choice of the regimen was upon the decision of the treating physician in accordance with the patient´s informed consent. Pts are median 70 years (yrs) old (range 21-90 yrs), 68% male, 42% have Binet stage C, 27% present with B symptoms, 13% with bulky disease and 66% with at least one comorbidity. Clinical and tumour characteristics differ between pts receiving BR or FCR: Pts treated with BR are older (median 71 vs. 65 yrs; p<0.0001) and present more often with Binet C (45% vs. 35%) or comorbidities (67% vs. 62%). Objective response rate (ORR) was assessed by the local site: 93% of pts receiving BR and 95% receiving FCR responded to 1st-line therapy; the clinical complete remission rate (CR) was reported to be 49% after BR and 39% after FCR, respectively. Both regimens were applied with median 6 cycles. In univariate analyses none of the parameters tested (type of 1st-line regimen, age, sex, B symptoms, bulky disease, tumour stage, comorbidities) had a significant impact on the response rate. Also, in a multivariate logistic regression model adjusted for the type of regimen (BR vs. FCR) and age neither factor had a significant impact on the response rate. At this point the small number of non-responders (n=17) precluded calculation of models adjusted for more than two parameters. After a median observation time of 17 months (maximum 40 mth), 93% of pts receiving BR are alive and 8% have received 2nd-line therapy. In pts receiving FCR 96% are alive and 6% have received 2nd-line therapy. Overall 5% of pts are lost to follow-up. Conclusion Our data show that previously untreated pts with CLL receiving BR or FCR in routine practice differ, with BR preferentially given to older pts with comorbidities. Nevertheless, response rates to 1st-line treatment with BR or FCR are comparable, even after statistical adjustment for age at the start of therapy. If the CLL10 trial confirms these results, BR could present an alternative 1st-line treatment to medically fit pts with CLL. BR: bendamustine + rituximab ± prednisone │ FCR: fludarabine + cyclophosphamide + rituximab ± prednisone Disclosures: Knauf: Mundipharma, Janssen, Roche Pharma: Consultancy, Honoraria.

Introduction Combination immunochemotherapy with cyclophosphamide, doxorubicine, vincristine, prednisone and the anti-CD20 monoclonal antibody rituximab (R-CHOP) is the standard of care for patients (pts) with previously untreated high-grade (aggressive) non-Hodgkin’s lymphoma (aNHL). Dose intensification of CHOP has shown ambiguous results (Pfreundschuh, 2004; Ohmachi, 2011), but the dose-dense two-weekly schedule (R-CHOP-14) was not found to be superior to the three-weekly schedule (R-CHOP-21) (Cunningham, 2013). Since clinical trials are restricted to highly selected pts, we investigated effectiveness of R-CHOP-14 and R-CHOP-21 in unselected pts with aNHL treated in routine practice by German office-based haematologists. Methods The open, longitudinal, multicentre, clinical registry on lymphoid neoplasms (TLN Registry, ClinicalTrial.gov registry NCT00889798) prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered by a network of over 260 German office-based haematologists. The choice of therapy is upon the discretion of the treating physician. All pts give their informed consent before onset of therapy. Pts are followed for 5 years. A broad set of data regarding patient and tumour characteristics, co-morbidities, all systemic treatments and response rates, date(s) of progression(s) and date of death are recorded. Automated plausibility and completeness checks with subsequently generated queries by the electronic data capture system ensure data reliability. In addition, data managers regularly check for plausibility and issue queries. Between May 2009 and August 2013 (date of present analysis), a total of 3,383 pts have been recruited. Results Of 477 pts with aNHL (95% DLBCL), recruited at the start of 1st-line therapy and treated with R-CHOP, 43% were treated with the two-weekly schedule (R-CHOP-14) and 57% received the three-weekly schedule (R-CHOP-21). Both schedules were applied for median 6 cycles (range 2-8); less than 6 cycles were applied in 23% and 30% of pts, respectively. Pts were median 67 years (yrs) old (33% ≤ 60 yrs), 47% female, 28% presented with tumour stage I (Ann Arbor), 27% with stage IV and 64% with at least one co-morbidity. 37% pts were of low risk (International Prognostic Index, IPI). Pts treated with the R-CHOP-14 or R-CHOP-21 differed in gender (female: 42% vs. 50%), performance status (ECOG 0: 44% vs. 40%) and pre-existing co-morbidities (60% vs. 67%), with no difference in age. Pts treated with R-CHOP-14 were diagnosed less often with tumour stage I (22% vs. 33%). Data on the application of Granulocyte colony-stimulating factor (G-CSF) were available for 381 pts. G-CSF was applied in 98% of pts treated with R-CHOP-14 and 61% of pts treated with R-CHOP-21. Pts treated with R-CHOP-21 and G-CSF were older (median 68 vs. 61yrs) than pts treated with R-CHOP-21 and no application of G-CSF. Objective response rate (ORR) as assessed by the local site was: 98% for R-CHOP-14 and 94% for R-CHOP-21; the clinical (unconfirmed) complete remission rate (CRu) was 65% for R- CHOP-14 and 70% for R-CHOP-21 (p=0.32). After a median follow-up of 22 months (maximum 51 months), 2-year progression-free survival rate (PFS) is 74% (1-year: 84%) for R-CHOP-14 and 82% (1-year: 85%) for R-CHOP-21. 2-year overall survival rate (OS) is 86% (1-year: 91%) for R-CHOP-14 and 85% (1-year: 89%) for R-CHOP-21. At time of analysis, 9% of pts (R-CHOP-14) and 8% (R-CHOP-21) have received a 2nd-line therapy. Overall, 7% of pts have been lost to follow-up. At this point, the high rate of pts alive without progression (>80%) precluded multivariate regression analyses regarding factors affecting PFS or OS. Conclusion Our data show that in routine practice, independent of age, pts with good performance status and low burden of co-morbities are more likely to receive the dose-dense two-weekly R-CHOP-14 schedule than the three-weekly R-CHOP-21 schedule as 1st-line treatment. First outcome data show that the effectiveness (ORR, PFS and OS) of both schedules is similar despite the differences in pts selection. DLBCL: Diffuse Large B-cell Lymphoma References: Cunningham et al., The Lancet. Mai 2013;381(9880):1817–26 │ Ohmachi K et al., Ann Oncol. 2011;22(6):1382–91 │ Pfreundschuh M et al., Blood. 2004;104(3):634–41 Disclosures No relevant conflicts of interest to declare.