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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:
  • Deutsche Krebshilfe
  • BMBF

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

Organisms: No Organisms specified

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

Leipzig Health Atlas PALs: Markus Löffler

Project created: 16th Apr 2019

Related items

LHA Data Portal Bot

Projects: Leipzig Health Atlas, LIFE- Leipzig Research Center for Civilization Diseases, German Lymphoma Alliance (GLA), German Competence Network Sepsis (SepNet)

Institutions: University of Leipzig

René Hänsel adminproject_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: Leipzig Health Atlas, German Consortium for Hereditary Breast and Ovarian Cancer, LIFE- Leipzig Research Center for Civilization Diseases, LIFE Adult, German Lymphoma Alliance (GLA), LIFE Head and Neck Cancer Group, Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, Genetical Statistics and Systems Biology, Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, German Consortium for Hereditary Non-Polyposis Colorectal Cancer, German Glioma Network, German Competence Network Sepsis (SepNet), Natural Language Processing for Clinical Research, LIFE Heart, Molecular mechanisms in malignant lymphoma, 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, LIFE Child, MMML-MYC-SYS, ProstataCA, COVID-19 Leipzig

Institutions: Institute for Medical Informatics, Statistics and Epidemiology

https://orcid.org/0000-0001-8344-0658
Markus Löffler pal

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

Institutions: Institute for Medical Informatics, Statistics and Epidemiology

Henry Löffler-Wirth project_administrator

Projects: LIFE Adult, German Lymphoma Alliance (GLA), German Glioma Network, Leipzig Melanoma Studies, MMML-MYC-SYS, COVID-19 Leipzig

Institutions: Interdisciplinary Center for Bioinformatics

https://orcid.org/0000-0001-8239-440X
Samira Zeynalova

Projects: German Lymphoma Alliance (GLA)

Institutions: Institute for Medical Informatics, Statistics and Epidemiology

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

RICOVER-noRTh
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

Submitter: 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

Submitter: 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

Submitter: 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

Submitter: 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)

Submitter: 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: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: ODM Data

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: ODM Data

Download
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
...

Creator: Marita Ziepert

Submitter: René Hänsel

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: H. Loeffler-Wirth, M. Kreuz, L. 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, M. Hummel, W. Klapper, R. Siebert, M. Loeffler, H. Binder

Date Published: 30th Apr 2019

Publication Type: Not specified

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, M. Ziepert, R. Herbrecht, J. Flament, T. Fu, B. Coiffier, C. R. Flowers

Date Published: 1st Sep 2018

Publication Type: Not specified

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, M. Ziepert, R. Herbrecht, J. Flament, T. Fu, C. R. Flowers, B. Coiffier

Date Published: 1st Aug 2018

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.
German Lymphoma Alliance (GLA)

Abstract (Expand)

Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined … activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.

Authors: B. Chapuy, C. Stewart, A. J. Dunford, J. Kim, A. Kamburov, R. A. Redd, M. S. Lawrence, M. G. M. Roemer, A. J. Li, M. Ziepert, A. M. Staiger, J. A. Wala, M. D. Ducar, I. Leshchiner, E. Rheinbay, A. Taylor-Weiner, C. A. Coughlin, J. M. Hess, C. S. Pedamallu, D. Livitz, D. Rosebrock, M. Rosenberg, A. A. Tracy, H. Horn, P. van Hummelen, A. L. Feldman, B. K. Link, A. J. Novak, J. R. Cerhan, T. M. Habermann, R. Siebert, A. Rosenwald, A. R. Thorner, M. L. Meyerson, T. R. Golub, R. Beroukhim, G. G. Wulf, G. Ott, S. J. Rodig, S. Monti, D. S. Neuberg, M. Loeffler, M. Pfreundschuh, L. Trumper, G. Getz, M. A. Shipp

Date Published: 2nd May 2018

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Obesity negatively impacts outcome in elderly female patients with aggressive B-cell lymphomas treated with R-CHOP: results from prospective trials of the German high grade non-Hodgkin's lymphoma trial group.
German Lymphoma Alliance (GLA)

Abstract (Expand)

To study if obesity is a risk factor in elderly patients (>60 years) with aggressive B-cell lymphoma, the outcomes of 576 elderly patients treated with rituximab in the RICOVER-60 trial were analysed … in a retrospective study with regard to body mass index (BMI) and gender. Of the 576 patients, 1% had low body weight (BMI < 18.5), 38% were normal weight (18.5 </= BMI < 25), 42% were overweight (25 </= BMI < 30) and 19% were obese (BMI >/= 30). Event-free (EFS), progression-free (PFS) and overall survival (OS) according to BMI showed no significant differences for all and for male patients. EFS (P = 0.041), PFS (P = 0.038) and OS (P = 0.031) were significantly better for female non-obese patients. A multivariate analysis adjusted for International Prognostic Index risk factors confirmed these results, with the following hazard ratios (HR) for obesity (BMI >/= 30) for EFS/PFS/OS: all patients - 1.4/1.4/1.4 (not significant); male patients - 1.2/1.2/1.0 (not significant) and female patients - 1.7 (P = 0.032)/1.9 (P = 0.022)/2.0 (P = 0.017). In conclusion, obesity is a risk factor that influences treatment outcome in elderly female patients with aggressive B-cell lymphoma treated with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone). The inferior outcomes in obese female patients may be due to faster rituximab clearance in obese females.

Authors: K. Hohloch, B. Altmann, M. Pfreundschuh, M. Loeffler, N. Schmitz, F. Zettl, M. Ziepert, L. Trumper

Date Published: 2nd Dec 2017

Publication Type: Not specified

Human Diseases: obesity, B-cell lymphoma

B-cell lymphoma
German Lymphoma Alliance (GLA), HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia

Taxonomy URI: http://purl.obolibrary.org/obo/DOID_707

Synonyms: B-cell lymphocytic neoplasm

Definitions: A non-Hodgkin lymphoma that has_material_basis_in B cells.

non-Hodgkin lymphoma
German Lymphoma Alliance (GLA), Molecular mechanisms in malignant lymphoma, MMML-MYC-SYS, Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia

Taxonomy URI: http://purl.obolibrary.org/obo/DOID_0060060

Definitions: A lymphoma that is characterized as any kind of lymphoma except Hodgkin's lymphoma., OMIM mapping confirmed by DO. [LS].

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