Evidence map›Paper›PMID 26315931›Full record

SynthesisHaematologica2015

Outcome of advanced chronic lymphocytic leukemia following different first-line and relapse therapies: a meta-analysis of five prospective trials by the German CLL Study Group (GCLLSG).

Paula Cramer, Susanne Isfort, Jasmin Bahlo, Stephan Stilgenbauer, Hartmut Döhner, Manuela Bergmann, Martina Stauch, Michael Kneba, Elisabeth Lange, Petra Langerbeins and 9 more

3 registry-linked trialsOpen access · goldAbstract readComparative StudyMeta-AnalysisMulticenter Study
In one paragraph

Synthesis in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00147901 phase2completednot on this map

Multicenter Phase II Trial of Fludarabine and Cyclophosphamide in Combination With Alemtuzumab (FC-Cam) for Patients With Relapsed Chronic Lymphocytic Leukemia - CLL-2L Protocol of the German CLL-Study Group (GCLLSG)

TypeinterventionalSponsorGerman CLL Study GroupRan2005 to 2011Enrolled61ConditionsB-cell Chronic Lymphocytic LeukemiaArmsFCCam
NCT00274989 phase2completednot on this map

Multicentre Phase II Trial of Bendamustine in Combination With Rituximab for Patients With Previously Untreated or Relapsed Chronic Lymphocytic Leukemia. CLL2M Protocol of the German CLL-Study Group (GCLLSG)

TypeinterventionalSponsorGerman CLL Study GroupRan2005 to 2011Enrolled195ConditionsChronic Lymphocytic LeukemiaArmsBendamustine, Rituximab
NCT00281918 phase3completednot on this map

Phase III Trial of Combined Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) Versus Chemotherapy With Fludarabine and Cyclophosphamide (FC) Alone in Patients With Previously Untreated Chronic Lymphocytic Leukaemia

TypeinterventionalSponsorHoffmann-La RocheRan2003 to 2011Enrolled817ConditionsLeukemiaArmsRituximab, Cyclophosphamide, Fludarabine Phosphate
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 36 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 2 countries.

Paula CramerDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany paula.cramer@uk-koeln.de.
Susanne IsfortDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany Department for Oncology, Hematology and Stem Cell Transplantation, University Hospital Aachen, Munich, Germany.
Jasmin BahloDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Stephan StilgenbauerDepartment III of Internal Medicine, University Hospital Ulm, Munich, Germany.
Hartmut DöhnerDepartment III of Internal Medicine, University Hospital Ulm, Munich, Germany.
Manuela BergmannDepartment of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Hospital Munich-Schwabing, Munich, Germany.
Martina StauchSpecialized Practice for Hematology and Oncology and Day Hospital, Kronach, Germany.
Michael KnebaDepartment II of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
Elisabeth LangeProtestant Hospital Hamm, Clinic for Hematology, Oncology and Palliative Care, Hamm, Germany.
Petra LangerbeinsDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Natali PflugDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Gabor KovacsDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Valentin GoedeDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Anna-Maria FinkDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Thomas ElterDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Kirsten FischerDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Clemens-Martin WendtnerDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Hospital Munich-Schwabing, Munich, Germany.
Michael HallekDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
Barbara EichhorstDepartment I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany.
University Hospital Cologne · DEUniversity of Cologne · DEIntegrated Oncology (United States) · USUniversity Hospital Ulm · DEEvangelisches Krankenhaus Hamm · DEUniversitätsklinikum Aachen · DEUniversity of Lübeck · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To evaluate the effect of first-line and subsequent therapies, the outcome of 1,558 patients with chronic lymphocytic leukemia from five prospective phase II/III trials conducted between 1999 and 2010 was analyzed. The 3-year overall survival rate was higher after first-line treatment with chemoimmunotherapies such as fludarabine/cyclophosphamide/rituximab (87.9%) or bendamustine/rituximab (90.7%) compared to chemotherapies without an antibody (fludarabine/cyclophosphamide: 84.6%; fludarabine: 77.5%; chlorambucil: 77.4%). Furthermore, the median overall survival was longer in patients receiving at least one antibody-containing regimen in any treatment line (94.4 months) compared to the survival in patients who never received an antibody (84.3 months, P<0.0001). Univariate Cox regression analysis demonstrated that patients who did receive antibody treatment had a 1.42-fold higher risk of death (hazard ratio, 1.42; 95% confidence interval: 1.185-1.694). Therapies administered at relapse were very heterogeneous. Only 55 of 368 patients (14.9%) who started second-line treatment >24 months after first-line therapy repeated the first-line regimen. Among 315 patients requiring treatment ≤24 months after first-line therapy, cyclophosphamide/doxorubicin/vincristine/prednisone with or without rituximab as well as alemtuzumab were the most commonly used therapies. In these early relapsing patients, the median overall survival was shorter following therapies containing an anthracycline and/or three or more cytotoxic agents (e.g. cyclophosphamide/doxorubicin/vincristine/prednisone or fludarabine/cyclophosphamide/mitoxantrone, 30.0 months) compared to single agent chemotherapy (e.g. fludarabine; 39.6 months) and standard chemoimmunotherapy (e.g. fludarabine/cyclophosphamide/rituximab: 61.6 months). In conclusion, the analysis confirms the superior efficacy of chemoimmunotherapies in patients with chronic lymphocytic leukemia. Moreover, the use of aggressive chemo(immuno)therapy combinations in patients with an early relapse does not offer any benefit when compared to less intensive therapies. Trial identifier: NCT00281918, ISRCTN75653261, ISRCTN36294212, NCT00274989 and NCT00147901.

Indexed as

AgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicCyclophosphamideDisease-Free SurvivalDoxorubicinFemaleHumansLeukemia, Lymphocytic, Chronic, B-CellMalePrednisoloneProspective StudiesRituximabVincristineCyclophosphamideDoxorubicinPrednisoloneRituximabVincristine

Identifiers

PMID26315931
PMCPMC4825288
OpenAlexW1910740057

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.