COCHRANE HAEMATOLOGICAL MALIGNANCIES GROUP NEWSLETTER

Transcription

1 F COCHRANE HAEMATOLOGICAL MALIGNANCIES GROUP NEWSLETTER Issue 4 October 2008 Welcome to our fourth newsletter! Inside this issue First Impact Factor for Cochrane Reviews News from the Editorial Base New Protocols and Reviews in 2008 Submission Dates CHMG Reviews of Individual Patient Data CHMG Website Relaunched CHMG Specialised Trials Register Meet the CHMG MANY THANKS! The Editorial Team thanks all Review Authors, Consumers, Editors as well as the Department I of Internal Medicine at the University Hospital of Cologne and the Sponsors, for their continued support and collaboration. FIRST IMPACT FACTOR FOR COCHRANE REVIEWS The first official Impact Factor (IF) for the Cochrane Database of Systematic Reviews (The Cochrane Library) has just been released. The 2007 Impact Factor (generated from citations in 2007 to reviews published in 2005 and 2006) is 4.654, which ranks CDSR 14 th out of the 100 journals in the ISI category Medicine, general and internal. This is a considerable achievement for The Cochrane Library, in its first year of ranking! We are optimistic that this news will encourage increasing numbers of authors to publish and maintain Cochrane reviews. All authors should cite Cochrane reviews as published in the Cochrane Database of Systematic Reviews, with the issue of publication. The Cochrane Haematological Malignancies Group (CHMG), based in Cologne, Germany, was founded in 2000 and is one of 52 groups that are part of The Cochrane Collaboration. The scope of the CHMG focuses on the diagnosis and treatment of haematological malignancies. The CHMG achieves funding from the BMBF (German Federal Ministry of Education and Research) to complete two systematic reviews on severe aplastic anaemia and Hodgkin s lymphoma.

2 Current Standings The last year has seen a number of changes in the CHMG staff and we have been able to enlarge the team at the editorial base. This should enable us to give current and future authors more support. The new staff at the base is introduced below. NEWS FROM THE EDITORIAL BASE KATHRIN BAUER The group s newest member is Kathrin who received her medical degree in Her work in the GIZ Nord poisons centre during the last four years has sparked an interest in Evidence-based medicine. Kathrin joined our group on the 1 st October and is looking forward to writing Cochrane Reviews. JULIA BOHLIUS Julia Bohlius left the Editorial Base in Cologne to take on new challenges at the University of Bern, Switzerland. She was one of the first members of the editorial base and the first to acquire and pass on methodology of Cochrane Reviews. We would like to thank her for her substantial contribution to the group s work over the past eight years! Fortunately, Julia will stick with us as CHMG content editor and review author! CORINNE BRILLANT Corinne is also new to the Cochrane Collaboration and joined our group in She received a degree in statistics in 2001 and is experienced with some of the group s topics due to her former position as statistician in the German Hodgkin s Study Group at the University Hospital of Cologne. Corinne is currently conducting and supporting statistical analyses for two IPD reviews. 2

3 URSULA GEORGI Ulla joined the group in 2007 as parttime group assistant and we are now enjoying her valuable support for the Editorial Base. CHRISTINE HERBST Christine joined the CHMG in June 2007 and is another newcomer to the Cochrane Collaboration. She is a medical doctor and obtained a MPH degree in Jerusalem. Christine is currently preparing reviews on infection prophylaxis in cancer patients. SABINE KLUGE Sabine, one of the former part-time consumer co-ordinators, was on maternity leave and rejoined the team in January She is now involved in the EPO- IPD meta-analysis and supports the preparation of reviews on different levels. INA MONSEF Finally, we were successful in finding a new Trials Search Coordinator! Ina studied library science and is also new to the Collaboration. She took over the vacant post in 2007 and supports review authors developing search strategies for systematic reviews. She optimised the process by the development of a stepby-step manual for reviewers. Furthermore, she maintains TIHO, a specialised trials register for haemato-oncology. NICOLE SKOETZ Nicole, a medical doctor, was also parttime consumer co-ordinator until In the meantime, she worked in the Coordinating Center for Clinical Trials Cologne (KKSK), a contract research organisation, as clinical project-manager and rejoined the CHMG in January She is now the review group co-ordinator and is delighted to be one of the six RGC executive members. CONSUMERS There is currently no consumer-coordinator position, and unfortunately we do not have resources for educational or other related projects at present. However, consumers interested to comment on CHMG protocols and reviews are always welcome and invited to contact us. Comments should be directed at patienten@chmg.de NEW PROTOCOLS AND REVIEWS IN 2008 As of October 2008, the CHMG published 14 systematic reviews and 22 protocols. A total of 70 review titles are registered with the Cochrane Collaboration and are in various stages of the editorial process. NEW REVIEWS High-dose chemotherapy with autologous stem cell transplantation in the first line treatment of aggressive Non-Hodgkin Lymphoma (NHL) in adults Greb A, Bohlius J, Schiefer D, Schwarzer G, Schulz H, Engert A. Cochrane Database of Systematic Reviews 2008, Issue 1. Plain language summary (excerpt) Aggressive Non-Hodgkin's Lymphomas (NHLs) are fast growing forms of lymphoma and are generally responsive to conventional cancer therapies such as chemotherapy and radiotherapy. The encouraging results in relapsed or progressive lymphoma led to the testing of high-dose chemotherapy (HDT) plus autologous transplantation as a primary therapy for the disease. We undertook this systematic review and meta-analysis to assess the effects of such treatment on overall survival and event free survival in patients with aggressive non-hodgkin lymphoma, in comparison to standard chemotherapy. The main results from this analysis are: 3

4 In general, there was no evidence that HDT improves overall survival or event free survival. In patients with good risk IPI there was some evidence for worse overall survival when treated with HDT. In contrast, there was suggestive but inconclusive evidence that poor risk patients may benefit from HDT. Overall, with respect to the large population included in our analyses (15 trials with 2728 patients) and the attempts made to minimise bias and confounding, we conclude that there is no evidence for a general benefit of the therapeutic principle of myeloablative chemotherapy followed by autologous stem cell transplantation for patients with aggressive NHL as first-line treatment based on the data presently available. Most importantly, IPI low-risk patients appear to be harmed by high-dose chemotherapy in first-line treatment. Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia Squizzato A, Romualdi E, Middeldorp S. Cochrane Database of Systematic Reviews 2008, Issue 2. Plain language summary Low-dose aspirin as an antiplatelet therapy is the drug of choice for preventing cardiovascular events, but the potential risk of bleeding has limited its use in myeloproliferative disorders in the past. This review of 630 people in two trials found that in patients with polycythaemia vera and with no clear indication or contraindication to aspirin therapy, the trial evidence suggests that low-dose aspirin reduces the risk of fatal thrombotic events, without an increased risk of major bleeding. No studies in patients with essential thrombocythaemia have been published. Corticosteroids for preventing graft-versus-host disease after allogeneic myeloablative stem cell transplantation Quellmann S, Schwarzer G, Hübel K, Greb A, Engert A, Bohlius J. Cochrane Database of Systematic Reviews 2008, Issue 3. Plain language summary Some types of blood cancer can be treated by transplanting stem cells from the patient's blood relatives or siblings. Unfortunately, transplanted stem cells (also called the 'graft') can sometimes induce an inflammatory reaction in the patient (or the 'host'). This reaction is called 'graft-versus-host disease' (GvHD), and once it occurs it is difficult to treat. GvHD can adversely affect the patient's quality of life and often causes death. Drug therapies have been developed to prevent GvHD. Even so, many patients still suffer this complication. Preventive therapy against GvHD must be optimised. Since corticosteroids are the first-line treatment used after GvHD occurs, it is a hypothesis that if used in prophylaxis regimens, corticosteroids can decrease the occurence of GvHD and improve patient survival rates. Five RCTs involving 604 people were included in this review. Analyses of these studies showed that the incidence of moderate forms of GvHD can be reduced by prophylactic corticosteroid regimens. However, there is no evidence that the incidence of life-threatening forms or patient mortality can be reduced. Effects on quality of life could not be estimated because this information was not systematically collected during these studies. Further studies are needed to determine if the timing of steroid administration influences the outcomes of GvHD. 4

5 NEW PROTOCOLS First-line double high-dose chemotherapy and autologous stem cell transplantation versus single high-dose chemotherapy and autologous stem cell transplantation in multiple myeloma (Protocol) Naumann F, Schnell R, Herbst C, Brillant C, Schulz H, Greb A, Bohlius JB, Djulbegovic B, Wheatley K, Engert A. Cochrane Database of Systematic Reviews 2008, Issue 1. Prophylactic antibiotics and G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy (Protocol) Herbst C, Naumann F, Kruse E, Knauel I, Schulz H, Bohlius J, Engert A. Cochrane Database of Systematic Reviews 2008, Issue 2. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin Lymphoma. (Protocol) Rehan FA, Bohlius J, Brillant C, Knauel I, Specht L, Engert A. Cochrane Database of Systematic Reviews 2008, Issue 2. Erythropoietin or Darbepoetin for patients with cancer - meta-analysis based on individual patient data (Protocol) Bohlius J, Trelle S, Weingart O, Schwarzer G, Brillant C, Clarke MJ, Djulbegovic B, Piper M, Rades D, Seidenfeld J, Somerfield M, Steensma D, Schumacher M, Engert A, Egger M. Cochrane Database of Systematic Reviews 2008, Issue 3. BECOMING A REVIEWER FOR THE CHMG If you are interested in preparing and maintaining a review for the CHMG, please contact our Review Group Co-ordinator Nicole (Nicole.skoetz@uk-koeln.de) for relevant information, and to discuss possible topics. SUBMISSION DATES Please remember that the editorial process takes at least 8 weeks, and that any items should be sent to us with plenty of time left. Obviously the sooner you send things to us the better. Deadlines for submitting items to the next libraries: Issue Copy Edit Support Module Submission Publication dates Issue 1, October November January 2009 Issue 2, January February April 2009 Issue 3, April May July 2009 Issue 4, July August October 2009 CHMG REVIEWS OF INDIVIDUAL PATIENT DATA Grants from the German Federal Ministry of Education and Research (BMBF) and from the German German Research Foundation (DFG) allow us to prepare four Cochrane reviews based on individual patient data (IPD). 1. Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk (Franklin, 2005) was our first IPD metaanalysis in which Franklin et al analysed data from 9,312 patients out of 37 trials. 2. The second IPD meta-analysis Identification of prognostic factors for patients with intermediate Hodgkin s disease: an individual patient data meta-analysis 5

6 aimed to identify prognostic factors in patients with intermediate stage Hodgkin s Lymphoma. Individual patient data were collected and risk factors for progression free survival identified using multivariate analysis (linear stepwise proportional hazards) stratified by study. Data from 4,490 adult patients enrolled between 08/1982 and 01/2003 were available for analysis (Bohlius et al, 2005). This review was conducted in close collaboration with the clinical and statistical experts of the German Hodgkin Study Group (GHSG). 3. The following two projects are based on previously published Cochrane reviews showing inconclusive effects (Bohlius, 2004; Bohlius, 2006; Greb, 2008). The literature-based meta-analyses conducted were mainly limited to published data aggregated across trials at the level of randomized groups. Pooled time-to-event analyses with IPD allow the examination of potential confounding and interaction, and are generally more efficient than analyses based on aggregated data. Individual patient data meta-analysis on the effects of erythropoiesisstimulating agents in cancer patients is one of these projects. It was a challenge to receive data from three pharmaceutical companies as well as from five independent investigators. For this project an international collaborative group was initiated. All analyses were predefined in a peer reviewed protocol (Bohlius, 2008) and a statistical analysis plan. An independent steering committee consisting of international experts in hematology, oncology, radiotherapy, epidemiology, medical statistics and consumer issues agreed on all analyses and interpretations. Independent investigators and representatives from manufacturers contributing data offered advice through the project s advisory board, but had no decision-making authority. Data were checked for accuracy, consistency, and completeness of follow-up. More than 13,000 patients enrolled in more than 50 studies were included in the meta-analysis, which is expected to be finalized this year. 4. The other ongoing IPD project is entitled High-dose chemotherapy plus autologous stem cell support in first-line treatment for aggressive Non-Hodgkin lymphoma. The role of high-dose chemotherapy in the treatment of aggressive lymphoma remains unclear so far. Several randomised controlled studies showed no significant benefit of this approach for the majority of patients, in some studies there are trends towards a better outcome of patients with a poor prognosis. Our previous mainly literature-based Cochrane Review (Greb, 2008) shows no evidence that HDCT improved overall survival or event free survival in low risk NHL patients and the evidence for poor risk patients is inconclusive. Thus, we extended our prior published Cochrane Review to an IPD Review. This IPD meta-analysis will be finished by the end of this year. In summary, preparing IPD Reviews require clinical and statistical expertise. Moreover, professional management of large international collaborative groups and proficiency in international legal and financial aspects are indispensable. The workload included in the conduct of IPD meta-analyses exceeds any literature-based review by far and requires adequate funding. The IPD meta-analyses outlined above were funded by: Hodgkin-IPD (secondary malignancies): DFG; Hodgkin-IPD: BMBF, No 01KG0610; Epo-IPD: BMBF, No 01KG0611; NHL- IPD: BMBF, No 01KG0604 CONTRIBUTIONS WELCOME If you like our newsletter, and you have information for our readers, why not join the team and write an article? Methodological issues, a new piece of research, work experience whatever your ideas, why not share them? Feel free to contact us info@chmg.de! 6

7 CHMG WEBSITE RELAUNCHED CHMG is pleased to announce the launch of the re-designed website. With improved navigation facilities the newly designed website continues to offer information on systematic reviews as well as resources for review authors and consumers, in English and in German. The new design has modernized the look and feel of CHMG offering an easier more enjoyable user experience. The site now includes an increased area with support material for Review authors and background information. It also includes sections covering ongoing projects and publications from the Editorial base. Check out new CHMG site! CHMG SPECIALISED TRIALS REGISTER After a 2-year-funding by the German Research Foundation (DFG), the CHMG and the German National Library of Medicine (ZBMed) decided to co-operate to maintain and expand the Specialised Trials Register to TIHO, a register for randomised and controlled clinical trials in haemato-oncology. This database is constantly updated and included citations that have been screened according to the guidelines of the Cochrane Collaboration and for their relevance to CHMG and are submitted quarterly to CENTRAL. TIHO, available at serves as a reliable source for evidence-based therapeutic decisions. The database contains about 6,500 relevant citations and is included in MedPilot, the German virtual library of medicine from the ZBMed ( It can be used worldwide free of charge by researchers and healthcare professionals. Trials are identified by a sensitive search strategy in the electronic bibliographic database MEDLINE and handsearching of conference proceedings. The following conference proceedings have already been entered into TIHO: American Society of Hematology (1990 onwards) American Society of Clinical Oncology 1985 to 1999, 2003 to

8 European Haematology Association (2000 onwards) International Symposium on Hodgkin's lymphoma (1998 onwards) Most of references are linked to the shelfmark of the German Library of Medicine, simplifying full text retrieval ( In the near future we will transfer the register into a study-based register. It will contain the same information but will link references that report on the same study. Furthermore the record of the study will contain additional information, which describe the study design, the participants or the outcome. This will be a great benefit for the authors. Searches of the specialised register can be arranged by contacting the TSC Ina (ina.monsef@uk-koeln.de). The register is also available for searching on the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library by using the term SR-HAEMATOL. MEET THE CHMG 16 th Cochrane Colloquium 3-7 Oct. in Freiburg, Germany If you are interested in the work of CHMG invite you to meet us during the Meet the Entities Session at Konzerthaus on Friday, Oct. 3, 14:15 16:30 Annual Meeting of DGHO, ÖGHO, SGMO, SGH Oct. in Vienna, Austria The next annual meeting of the German, Austrian and Swiss Societies for Haematology and Oncology will be organized by the Austrian Society for Hematology and Oncology. We extend a warm inviation to our Cochrane symposium on Sunday, Oct. 12, 16:30 18: th ASH Annual Meeting 6 9 Dec. in San Francisco, California Each December, the Society's annual meeting provides haematologists from around the world a forum for discussing critical issues in haematology. Nearly 20,000 clinicians, scientists, and others attend the four-day meeting, which consists of a superb educational program and cutting-edge scientific sessions. EDITORS CO-ORDINATING EDITOR Andreas Engert, Germany Julia Bohlius, Switzerland Benjamin Djulbegovic, USA Auro di Giglio, Brazil Pia Raanani, Israel Sue Richards, UK Guido Schwarzer, Germany Lena Specht, Denmark Keith Wheatley, UK EDITORIAL BASE IN COLOGNE CO-ORDINATING EDITOR Andreas Engert REVIEW GROUP CO-ORDINATOR Nicole Skoetz TRIALS SEARCH CO-ORDINATOR Ina Monsef STATISTICIAN Corinne Brillant RESEARCH FELLOWS Kathrin Bauer Christine Herbst Sabine Kluge Olaf Weingart TEAM ASSISTANCE Ursula Georgi 8