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German Lymphoma Alliance (GLA)

Overview
Description:

B-cell lymphoma is the most frequent lymphoid neoplasia accounting for one third of all lymphomas. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) is the current treatment standard, leading to high cure rates especially in younger patients. Although the 3-year event-free survival is about 60% even for elderly patients between 60-80 years old, the remainder of patients eventually relapse and the majority die of their disease. The German Non-Hodgkin's Lymphoma Study Group (DSHNHL) was founded in 1993 and has since conducted more than 25 national and international trials including more than 8000 patients in first line and salvage therapies. The DSHNHL is a network of haematooncologists, pathologists, radiologists, radiotherapists, nuclear physicians, biologists, geneticists and biometricians. All results of clinical trials performed by the DSHNHL were published in international journals and could lead a contribution to improve the treatment results.

Programme: NHL

LHA-ID: 7RX4165T77-8

Funding codes:
  • BMBF
  • Deutsche Krebshilfe

Public web page: https://www.dshnhl.org

Human Diseases: Non-hodgkin lymphoma, B-cell lymphoma

Leipzig Health Atlas PALs: Markus Löffler

Project Coordinators: No Project coordinators for this Project

Project created: 16th Apr 2019

Project Hierarchy

Related items

Christoph Beger adminasset_housekeeper

Projects: LIFE- Leipzig Research Center for Civilization Diseases, Leipzig Health Atlas, Onto-Med Research Group, German Lymphoma Alliance (GLA)

Institutions: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

https://orcid.org/0000-0002-1166-0368
René Hänsel adminproject_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: Leipzig Health Atlas, LIFE Adult, LIFE- Leipzig Research Center for Civilization Diseases, LIFE Head and Neck Cancer Group, LIFE Heart, Molecular mechanisms in malignant lymphoma, German Lymphoma Alliance (GLA), Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, German Consortium for Hereditary Breast and Ovarian Cancer, German Consortium for Hereditary Non-Polyposis Colorectal Cancer, MMML-MYC-SYS, Natural Language Processing for Clinical Research, Genetical Statistics and Systems Biology, German Competence Network Sepsis (SepNet), LIFE Child, Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, ProstataCA

Institutions: Institute for Medical Informatics, Statistics and Epidemiology

https://orcid.org/0000-0001-8344-0658
Markus Kreuz project_administrator: inactive since

Projects: LIFE Head and Neck Cancer Group, LIFE- Leipzig Research Center for Civilization Diseases, LIFE Heart, Molecular mechanisms in malignant lymphoma, German Lymphoma Alliance (GLA), MMML-MYC-SYS, German Glioma Network

Institutions: Institute for Medical Informatics, Statistics and Epidemiology

Markus Löffler pal

Projects: Leipzig Health Atlas, LIFE Adult, LIFE- Leipzig Research Center for Civilization Diseases, LIFE Head and Neck Cancer Group, Molecular mechanisms in malignant lymphoma, German Lymphoma Alliance (GLA), Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, MMML-MYC-SYS, German Competence Network Sepsis (SepNet), HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, SMITH

Institutions: Institute for Medical Informatics, Statistics and Epidemiology

Henry Löffler-Wirth project_administrator

Projects: Leipzig Melanoma Studies, German Lymphoma Alliance (GLA), MMML-MYC-SYS, German Glioma Network, LIFE Adult, LIFE- Leipzig Research Center for Civilization Diseases

Institutions: Interdisciplinary Center for Bioinformatics

https://orcid.org/0000-0001-8239-440X
Morphometric image analysis of IHC stained lymphoma tissue samples
Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

ROF filter based segmentation methods will be employed for automated recognition of macrophages, B-cells and cell nuclei within the tissue samples.

Snapshots: No snapshots

MegaCHOEP Phase III
German Lymphoma Alliance (GLA)

Mega-CHOEP phase III is a randomised study comparing conventional chemoimmunotherapy with R-CHOEP-14 with high-dose chemotherapy plus Rituximab with autologous stem cell transplantation in high-risk patients aged 61 to 80 years with Aggressive Non-Hodgkin’s Lymphoma.

Snapshots: No snapshots

RICOVER-60
German Lymphoma Alliance (GLA)

RICOVER-60 is a randomised study comparing 6 and 8 cycles of chemotherapy with CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) at 14-day intervals (CHOP-14), both with or without the monoclonal anti-CD20 antibody Rituximab in patients aged 61 to 80 years with Aggressive Non-Hodgkin’s Lymphoma.

Snapshots: No snapshots

SEXIE-R-CHOP-14
German Lymphoma Alliance (GLA)

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)

Snapshots: No snapshots

SMARTE-R-CHOP-14
German Lymphoma Alliance (GLA)
No description specified

Snapshots: No snapshots

HighCHOEP phase 2
German Lymphoma Alliance (GLA)
No description specified

Person responsible: René Hänsel

Snapshots: No snapshots

Study type: Not specified

HighCHOEP
German Lymphoma Alliance (GLA)
No description specified

Person responsible: René Hänsel

Snapshots: No snapshots

Study type: Not specified

NHL-B2
German Lymphoma Alliance (GLA)
No description specified

Person responsible: René Hänsel

Snapshots: No snapshots

Study type: Not specified

NHL-B1
German Lymphoma Alliance (GLA)
No description specified

Person responsible: René Hänsel

Snapshots: No snapshots

Study type: Not specified

MegaCHOEP Phase III
German Lymphoma Alliance (GLA)

Mega-CHOEP phase III is a randomised study comparing conventional chemoimmunotherapy with R-CHOEP-14 with high-dose chemotherapy plus Rituximab with autologous stem cell transplantation in high-risk patients aged 61 to 80 years with Aggressive Non-Hodgkin’s Lymphoma.

Person responsible: René Hänsel

Snapshots: No snapshots

Study type: Not specified

SMARTE-R-CHOP-14 trial data
German Lymphoma Alliance (GLA)

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)
Sample Size: 189

Contributor: René Hänsel

Assay type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

SMARTE-R-CHOP-14 metadata
German Lymphoma Alliance (GLA)

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)
Sample Size: 189

Contributor: René Hänsel

Assay type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

SEXIE-R-CHOP-14 trial data
German Lymphoma Alliance (GLA)

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)
Sample Size: 268

Contributor: René Hänsel

Assay type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

SEXIE-R-CHOP-14 metadata
German Lymphoma Alliance (GLA)

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)
Sample Size: 268

Contributor: René Hänsel

Assay type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

RICOVER-noRTh trial data
German Lymphoma Alliance (GLA)

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)

Contributor: René Hänsel

Assay type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

SMARTE-R-CHOP-14 trial data-CSV
German Lymphoma Alliance (GLA)
No description specified

Creator: René Hänsel

Contributor: René Hänsel

Data file type: Clinical Data

SMARTE-R-CHOP-14 trial data-SPSS
German Lymphoma Alliance (GLA)
No description specified

Creator: René Hänsel

Contributor: René Hänsel

Data file type: Clinical Data

SMARTE-R-CHOP-14 trial data-ODM
German Lymphoma Alliance (GLA)
No description specified

Creator: René Hänsel

Contributor: René Hänsel

Data file type: ODM Data

SMARTE-R-CHOP-14 metadata-XLSX
German Lymphoma Alliance (GLA)
No description specified

Creator: René Hänsel

Contributor: René Hänsel

Data file type: Clinical Data

Download
SMARTE-R-CHOP-14 metadata-ODM
German Lymphoma Alliance (GLA)
No description specified

Creator: René Hänsel

Contributor: René Hänsel

Data file type: ODM Data

Download
1 hidden item
Haematotox calculator
German Lymphoma Alliance (GLA)

Introduction
On this homepage we provide a web-based tool to calculate prognostic scores on haematopoietic toxicity for 6 cycles CHOP-like regimen in patients with aggressive NHL. As we used for this analysis the data collected within the NHL-B1 and NHL-B2 trials of the DSHNHL as described in detail in Pfreundschuh et al. the predictions are valid for similar patient populations.

Description
We offer two types of models. Pre-treatment models include beside the therapy regimen only prognostic
...

Creators: René Hänsel, Marita Ziepert

Contributor: René Hänsel

ROF filter based macrophage segmentation in IHC stained tissue samples: MATLAB procedures
Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

This is a set of MATLAB procedures for automated segmentation and counting of macrophages in multiple IHC stained tissue samples.
Execution assumes that three aligned single-channel greyscale images of a given tissue area are available, representing IHC stainings with CD14 and CD163 antibodies (targeting macrophages) as well as DAPI staining (targeting cell cores). After detection of evaluation subregion (based on DAPI channel information), IHC stained macrophages will be masked and counted (based
...

Creators: René Hänsel, Marcus Wagner

Contributor: René Hänsel

Download
An image dataset related to automated macrophage detection in immunostained lymphoma tissue samples
Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

Abstract (Expand)

A large set of IHC stained DLBCL specimens is provided together with segmentation masks for different cell populations generated by a reference method for automated image analysis, thus featuring … considerable reuse potential. Provided image data comprise a) fluorescence microscopy images of 44 multiple immunohistostained DLBCL tumor subregions, captured at four channels corresponding to CD14, CD163, Pax5 and DAPI; b) cartoon-filtered versions of these images, generated by Rudin-Osher-Fatemi (ROF) denoising; c) an automatically generated mask of the evaluation subregion, based on information from the DAPI channel, and d) automatically generated segmentation masks for macrophages, B-cells and the total of cell nuclei, using information from CD14, CD163, Pax5 and DAPI channels, respectively.

Authors: Marcus Wagner, Sarah Reinke, René Hänsel, Wolfram Klapper, Ulf-Dietrich Braumann

Date Published: No date defined

Journal: Not specified

Human Diseases: diffuse large B-cell lymphoma

Automated macrophage counting in DLBCL tissue samples: a ROF filter based approach
Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

Abstract (Expand)

We describe a Rudin-Osher-Fatemi (ROF) filter based segmentation approach for whole tissue samples, combining floating intensity thresholding and rule-based feature detection. Method is validated against … manual counts and compared with two commercial software kits (Tissue Studio 64, Definiens AG, and Halo, Indica Labs) and a straightforward machine-learning approach in a set of 50 test images. Further, the novel method and both commercial packages are applied to a set of 44 whole tissue sections. Outputs are compared with gene expression data available for the same tissue samples. Finally, the ROF based method is applied to 44 expert-specified tumor subregions for testing selection and subsampling strategies. Our method is deterministic, fully automated, externally repeatable, independent on training data and -- in difference to most commercial software kits -- completely documented. Among all tested methods, the novel approach is best correlated with manual count (0.9297). Automated detection of evaluation subregions proved to be fully reliable. Subsampling within tumor subregions is possible with results almost identical to full sampling. Comparison with gene expression data obtained for the same tissue samples reveals only moderate to low correlation levels, thus indicating that image morphometry constitutes an independent source of information about antibody-polarized macrophage occurence and distribution.

Authors: Marcus Wagner, René Hänsel, Sarah Reinke, Julia Richter, Michael Altenbuchinger, Ulf-Dietrich Braumann, Rainer Spang, Markus Löffler, Wolfram Klapper

Date Published: No date defined

Journal: Biological Procedures Online

Human Diseases: diffuse large B-cell lymphoma

A modular transcriptome map of mature B cell lymphomas.
German Lymphoma Alliance (GLA), MMML-MYC-SYS

Abstract (Expand)

BACKGROUND: Germinal center-derived B cell lymphomas are tumors of the lymphoid tissues representing one of the most heterogeneous malignancies. Here we characterize the variety of transcriptomic … phenotypes of this disease based on 873 biopsy specimens collected in the German Cancer Aid MMML (Molecular Mechanisms in Malignant Lymphoma) consortium. They include diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt's lymphoma, mixed FL/DLBCL lymphomas, primary mediastinal large B cell lymphoma, multiple myeloma, IRF4-rearranged large cell lymphoma, MYC-negative Burkitt-like lymphoma with chr. 11q aberration and mantle cell lymphoma. METHODS: We apply self-organizing map (SOM) machine learning to microarray-derived expression data to generate a holistic view on the transcriptome landscape of lymphomas, to describe the multidimensional nature of gene regulation and to pursue a modular view on co-expression. Expression data were complemented by pathological, genetic and clinical characteristics. RESULTS: We present a transcriptome map of B cell lymphomas that allows visual comparison between the SOM portraits of different lymphoma strata and individual cases. It decomposes into one dozen modules of co-expressed genes related to different functional categories, to genetic defects and to the pathogenesis of lymphomas. On a molecular level, this disease rather forms a continuum of expression states than clearly separated phenotypes. We introduced the concept of combinatorial pattern types (PATs) that stratifies the lymphomas into nine PAT groups and, on a coarser level, into five prominent cancer hallmark types with proliferation, inflammation and stroma signatures. Inflammation signatures in combination with healthy B cell and tonsil characteristics associate with better overall survival rates, while proliferation in combination with inflammation and plasma cell characteristics worsens it. A phenotypic similarity tree is presented that reveals possible progression paths along the transcriptional dimensions. Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt's lymphoma and particularly on 'double-hit' MYC and BCL2 transformed lymphomas. CONCLUSIONS: The transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities.

Authors: Henry Löffler-Wirth, Markus Kreuz, Lydia Hopp, A. Arakelyan, A. Haake, S. B. Cogliatti, A. C. Feller, M. L. Hansmann, D. Lenze, P. Moller, H. K. Muller-Hermelink, E. Fortenbacher, E. Willscher, G. Ott, A. Rosenwald, C. Pott, C. Schwaenen, H. Trautmann, S. Wessendorf, H. Stein, M. Szczepanowski, L. Trumper, Michael Hummel, W. Klapper, R. Siebert, Markus Löffler, Hans Binder

Date Published: 30th Apr 2019

Journal: Genome Med

Human Diseases: B-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Burkitt lymphoma

Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient-Level Analysis of Multiple Randomized Trials (SEAL).
German Lymphoma Alliance (GLA)

Abstract (Expand)

Purpose Overall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An … earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL. Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R(2)WLS) and Copula bivariable ( R(2)Copula) models. Prespecified criteria for surrogacy required either R(2)WLS or R(2)Copula >/= 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60. Results Trial-level surrogacy for PFS was strong ( R(2)WLS = 0.83; R(2)Copula = 0.85) and met the predefined criteria for surrogacy. At the patient level, PFS strongly correlated with OS. The surrogate threshold effect had a hazard ratio of 0.89. Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials. Trial-level surrogacy for PFS24 was relatively strong ( R(2)WLS = 0.77; R(2)Copula = 0.78) but did not meet prespecified criteria. At the patient level, PFS24 significantly correlated with OS. The surrogate threshold effect had an odds ratio of 1.51. Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future randomized controlled trials evaluating chemoimmunotherapy in DLBCL. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.

Authors: Q. Shi, N. Schmitz, F. S. Ou, J. G. Dixon, D. Cunningham, M. Pfreundschuh, J. F. Seymour, U. Jaeger, T. M. Habermann, C. Haioun, H. Tilly, H. Ghesquieres, F. Merli, Marita Ziepert, R. Herbrecht, J. Flament, T. Fu, B. Coiffier, C. R. Flowers

Date Published: 1st Sep 2018

Journal: J Clin Oncol

Human Diseases: diffuse large B-cell lymphoma

Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials.
German Lymphoma Alliance (GLA)

Abstract (Expand)

Background: Patients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed … overall survival (OS) stratified by progression-free survival (PFS) at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration. Patients and methods: PFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs). Results: A total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0-34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively. Conclusion: Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.

Authors: M. J. Maurer, T. M. Habermann, Q. Shi, N. Schmitz, D. Cunningham, M. Pfreundschuh, J. F. Seymour, U. Jaeger, C. Haioun, H. Tilly, H. Ghesquieres, F. Merli, Marita Ziepert, R. Herbrecht, J. Flament, T. Fu, C. R. Flowers, B. Coiffier

Date Published: 1st Aug 2018

Journal: Ann Oncol

Human Diseases: diffuse large B-cell lymphoma

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