NHL

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Web page: Not specified

Funding details:
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Related items

GLA - German Lymphoma Alliance

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 ...

Programme: NHL

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

HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia

In the interdisciplinary consortium HaematoSys partners from leading clinical haematooncological study groups, pathologists, geneticists, cell biologists as well as mathematicians, statisticians and bioinformaticians have joined forces.

Programme: NHL

Public web page: https://www.haematosys.de

ACT-2
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Studies: ACT-2

Resources: ACT-2 trial data, ACT-2 trial metadata

FLYER
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Studies: Flyer

Resources: FLYER trial data, FLYER trial metadata

MegaCHOEP Phase III
GLA - German Lymphoma Alliance

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.

Submitter: René Hänsel

Studies: MegaCHOEP Phase III

Resources: No Resources

RICOVER-60
GLA - German Lymphoma Alliance

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.

Submitter: René Hänsel

Studies: RICOVER-60

Resources: RICOVER-60 trial data, RICOVER-60 trial metadata

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

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

Submitter: René Hänsel

Studies: SEXIE-R-CHOP-14

Resources: SEXIE-R-CHOP-14 metadata, SEXIE-R-CHOP-14 trial data

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

Submitter: René Hänsel

Studies: SMARTE-R-CHOP-14

Resources: SMARTE-R-CHOP-14 metadata, SMARTE-R-CHOP-14 trial data

RICOVER-noRTh
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Studies: RICOVER-noRTh

Resources: RICOVER-noRTh metadata, RICOVER-noRTh trial data

NHL-B2
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Studies: NHL-B2

Resources: No Resources

NHL-B1
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Studies: NHL-B1

Resources: No Resources

MInT
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Studies: MInT

Resources: MInT trial data, MInt Trial Result Metadata

Flyer
GLA - German Lymphoma Alliance

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

Submitter: René Hänsel

Investigation: FLYER

Resources: FLYER trial data, FLYER trial metadata

Study type: Not specified

ACT-2
GLA - German Lymphoma Alliance

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

Submitter: René Hänsel

Investigation: ACT-2

Resources: ACT-2 trial data, ACT-2 trial metadata

Study type: Not specified

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

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

Submitter: René Hänsel

Investigation: SEXIE-R-CHOP-14

Resources: SEXIE-R-CHOP-14 metadata, SEXIE-R-CHOP-14 trial data

Study type: Not specified

HighCHOEP phase 2
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Investigation: HighCHOEP phase 2

Resources: No Resources

Study type: Not specified

HighCHOEP
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Investigation: HighCHOEP

Resources: No Resources

Study type: Not specified

NHL-B2
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Investigation: NHL-B2

Resources: No Resources

Study type: Not specified

NHL-B1
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Investigation: NHL-B1

Resources: No Resources

Study type: Not specified

MegaCHOEP Phase III
GLA - German Lymphoma Alliance

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.

Submitter: René Hänsel

Investigation: MegaCHOEP Phase III

Resources: No Resources

Study type: Not specified

Pegfilgrastim
GLA - German Lymphoma Alliance

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival) Sample Size: 103

Submitter: René Hänsel

Investigation: Pegfilgrastim

Resources: Pegfilgrastim metadata, Pegfilgrastim trial data

Study type: Not specified

RICOVER-noRTh
GLA - German Lymphoma Alliance

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

Submitter: René Hänsel

Investigation: RICOVER-noRTh

Resources: RICOVER-noRTh metadata, RICOVER-noRTh trial data

Study type: Not specified

ACT-2 trial metadata
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: ACT-2

Study: ACT-2

FLYER trial data
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: FLYER

Study: Flyer

FLYER trial metadata
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: FLYER

Study: Flyer

ACT-2 trial data
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: ACT-2

Study: ACT-2

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

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

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: SMARTE-R-CHOP-14

Study: SMARTE-R-CHOP-14

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

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

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: SMARTE-R-CHOP-14

Study: SMARTE-R-CHOP-14

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

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

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: SEXIE-R-CHOP-14

Study: SEXIE-R-CHOP-14

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

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

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: SEXIE-R-CHOP-14

Study: SEXIE-R-CHOP-14

RICOVER-noRTh trial data
GLA - German Lymphoma Alliance

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

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: RICOVER-noRTh

Study: RICOVER-noRTh

RICOVER-noRTh metadata
GLA - German Lymphoma Alliance
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: RICOVER-noRTh

Study: RICOVER-noRTh

Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial.
GLA - German Lymphoma Alliance

Abstract (Expand)

PTCL patients exhibit poor survival with existing treatments. We investigated the efficacy of CHOP combined with alemtuzumab in 116 PTCL patients age 61-80 in an open-label, randomized phase 3 trial. … Alemtuzumab was given on day 1, to a total of 360 mg in 21 patients, or 120 mg in 37. Hematotoxicity was increased with A-CHOP resulting in more grade >/=3 infections (40% versus 21%) and 4 versus 1 death due to infections, respectively. CR/CRu rate was 60% for A-CHOP and 43% for CHOP, and OR rate was 72% and 66%, respectively. Three-year-EFS, PFS and OS were 27% [15%-39%], 28% [15%-40%], and 37% ([23%-50%] for A-CHOP, and 24% [12%-35%], 29% [17%-41%], and 56% [44%-69%] for CHOP, respectively, showing no significant differences. Multivariate analyses, adjusted for strata and sex confirmed these results (hazard ratio HREFS: 0.7 ([95% CI: 0.5-1.1]; p = 0.094), HRPFS: 0.8 ([95% CI: 0.5-1.2]; p = 0.271), HROS: 1.4 ([95% CI: 0.9-2.4]; p = 0.154). The IPI score was validated, and male sex (HREFS 2.5) and bulky disease (HREFS 2.2) were significant risk factors for EFS, PFS, and OS. Alemtuzumab added to CHOP increased response rates, but did not improve survival due to treatment-related toxicity.

Authors: G. G. Wulf, B. Altmann, M. Ziepert, F. D'Amore, G. Held, R. Greil, O. Tournilhac, T. Relander, A. Viardot, M. Wilhelm, C. Wilhelm, A. Pezzutto, J. M. Zijlstra, E. V. D. Neste, P. J. Lugtenburg, J. K. Doorduijn, M. V. Gelder, G. W. van Imhoff, F. Zettl, F. Braulke, M. Nickelsen, B. Glass, A. Rosenwald, P. Gaulard, M. Loeffler, M. Pfreundschuh, N. Schmitz, L. Trumper

Date Published: 10th May 2020

Publication Type: Journal article

Human Diseases: lymphoma, peripheral T-cell lymphoma

Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, … we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. METHODS: This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7.5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m(2)), doxorubicin (50 mg/m(2)), and vincristine (1.4 mg/m(2), with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m(2) of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of -5.5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. FINDINGS: Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. INTERPRETATION: In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. FUNDING: Deutsche Krebshilfe.

Authors: V. Poeschel, G. Held, M. Ziepert, M. Witzens-Harig, H. Holte, L. Thurner, P. Borchmann, A. Viardot, M. Soekler, U. Keller, C. Schmidt, L. Truemper, R. Mahlberg, R. Marks, H. G. Hoeffkes, B. Metzner, J. Dierlamm, N. Frickhofen, M. Haenel, A. Neubauer, M. Kneba, F. Merli, A. Tucci, P. de Nully Brown, M. Federico, E. Lengfelder, A. di Rocco, R. Trappe, A. Rosenwald, C. Berdel, M. Maisenhoelder, O. Shpilberg, J. Amam, K. Christofyllakis, F. Hartmann, N. Murawski, S. Stilgenbauer, M. Nickelsen, G. Wulf, B. Glass, N. Schmitz, B. Altmann, M. Loeffler, M. Pfreundschuh

Date Published: 21st Dec 2019

Publication Type: Journal article

Human Diseases: lymphoma, diffuse large B-cell lymphoma

A modular transcriptome map of mature B cell lymphomas.
GLA - German Lymphoma Alliance, MMML-MYC-SYS, oBIG - omics Bioinformatics for Health

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).
GLA - German Lymphoma Alliance

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.
GLA - German Lymphoma Alliance

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.
GLA - German Lymphoma Alliance

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.
GLA - German Lymphoma Alliance

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

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial.
GLA - German Lymphoma Alliance

Abstract (Expand)

Background: The prognosis of elderly patients with aggressive B-non-Hodgkin's lymphoma after first lymphoma-related treatment failure (TF-L) is not well described. Methods: We analysed patient … characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial. Results: TF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (</=12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen. Conclusion: MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

Authors: B. Glass, A. J. Dohm, L. H. Truemper, M. Pfreundschuh, A. Bleckmann, G. G. Wulf, A. Rosenwald, M. Ziepert, N. Schmitz

Date Published: 1st Dec 2017

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients.
GLA - German Lymphoma Alliance

Abstract (Expand)

Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL … patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m(2) , females 375 mg/m(2) ) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m(2) dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m(2) was not more toxic than 375 mg/m(2) rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.

Authors: M. Pfreundschuh, N. Murawski, S. Zeynalova, M. Ziepert, M. Loeffler, M. Hanel, J. Dierlamm, U. Keller, M. Dreyling, L. Truemper, N. Frickhofen, A. N. Hunerliturkoglu, N. Schmitz, V. Poschel, T. Rixecker, C. Berdel, C. Rube, G. Held, C. Zwick

Date Published: 11th Oct 2017

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

TP53 mutation and survival in aggressive B cell lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

TP53 is mutated in 20-25% of aggressive B-cell lymphoma (B-NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 … mutation to current risk models in aggressive B-NHL, we investigated TP53 gene mutations within the RICOVER-60 trial. Of 1,222 elderly patients (aged 61-80 years) enrolled in the study and randomized to six or eight cycles of CHOP-14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index-Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B-symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event-free (EFS), progression-free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI-factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed.

Authors: T. Zenz, M. Kreuz, M. Fuge, W. Klapper, H. Horn, A. M. Staiger, D. Winter, H. Helfrich, J. Huellein, M. L. Hansmann, H. Stein, A. Feller, P. Moller, N. Schmitz, L. Trumper, M. Loeffler, R. Siebert, A. Rosenwald, G. Ott, M. Pfreundschuh, S. Stilgenbauer

Date Published: 1st Oct 2017

Publication Type: Journal article

Human Diseases: non-Hodgkin lymphoma, B-cell lymphoma

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

RICOVER-60 trial data-CSV
GLA - German Lymphoma Alliance

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Not specified

FLYER trial data SPSS
GLA - German Lymphoma Alliance
No description specified

Creator: René Hänsel

Submitter: René Hänsel

Data file type: Clinical Data

Human Diseases: lymphoma

RICOVER-noRTh trial data-CSV
GLA - German Lymphoma Alliance

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

RICOVER-60 trial data-SPSS
GLA - German Lymphoma Alliance

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Not specified

Pegfilgrastim trial data-CSV
GLA - German Lymphoma Alliance
No description specified

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

Pegfilgrastim trial data-SPSS
GLA - German Lymphoma Alliance
No description specified

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

SEXIE-R-CHOP-14 trial data-CSV
GLA - German Lymphoma Alliance
No description specified

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: Clinical Data

RICOVER-noRTh trial data-ODM
GLA - German Lymphoma Alliance

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

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: ODM Data

Pegfilgrastim trial data-ODM
GLA - German Lymphoma Alliance
No description specified

Creator: Marita Ziepert

Submitter: René Hänsel

Data file type: ODM Data

Haematotox calculator
GLA - German Lymphoma Alliance

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

External Link
LHA Data Portal Bot

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

Institutions: University of Leipzig

René Hänsel adminproject_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: LHA - Leipzig Health Atlas, LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, LIFE Heart, MMML - Molecular mechanisms in malignant lymphoma, GLA - German Lymphoma Alliance, MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, HaematoOpt - Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, e:Med, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, MMML-MYC-SYS, NLP4CR - Natural Language Processing for Clinical Research, Genetical Statistics and Systems Biology, SepNet - German Competence Network Sepsis, LIFE Child, HNPCC-Sys - Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, GGN - German Glioma Network, CAPSys - Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, CapSys - Systems Medicine of Community Acquired Pneumonia, ProstataCA, HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, SMITH - Smart Medical Information Technology for Healthcare, Task Force COVID-19 Leipzig, NFDI4Health, POLAR - Polypharmacy, Drug Interactions, Risks, Management of health information systems, LivSys Transfer - Transfer of the LivSys in vitro system for hepatotoxicity into application, Project Test Demonstrator, Fundus photography as tool for analysis of eyes of subjects with diabetes, Clinical Trials Leipzig, NFDI4Health - TA3 Services, STOP-NUC, SCALE-TORT, EarlyAMDRate

Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)

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

Projects: LHA - Leipzig Health Atlas, LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, MMML - Molecular mechanisms in malignant lymphoma, GLA - German Lymphoma Alliance, MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, MMML-MYC-SYS, Genetical Statistics and Systems Biology, SepNet - German Competence Network Sepsis, HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, e:Med, SMITH - Smart Medical Information Technology for Healthcare, Task Force COVID-19 Leipzig, NFDI4Health, POLAR - Polypharmacy, Drug Interactions, Risks

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

Henry Löffler-Wirth project_administratorprogramme_administrator

Projects: Leipzig Melanoma Studies, GLA - German Lymphoma Alliance, MMML-MYC-SYS, GGN - German Glioma Network, LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, Task Force COVID-19 Leipzig, NFDI4Health, LHA - Leipzig Health Atlas, Think different, imSAVAR - Immune safety avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies, oBIG - omics Bioinformatics for Health, Vine Bioinformatics - grape genomics for Innovative viticulture

Institutions: University of Leipzig, Interdisciplinary Center for Bioinformatics (IZBI)

https://orcid.org/0000-0001-8239-440X
Beate Mann

Projects: GLA - German Lymphoma Alliance

Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)

Samira Zeynalova

Projects: GLA - German Lymphoma Alliance

Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)

Marita Ziepert project_administrator

Projects: GLA - German Lymphoma Alliance

Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)

B-cell lymphoma
GLA - German Lymphoma Alliance, 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
GLA - German Lymphoma Alliance, MMML - Molecular mechanisms in malignant lymphoma, HaematoOpt - Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, MMML-MYC-SYS, 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].

hematopoietic system disease
HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia

Taxonomy URI: http://purl.obolibrary.org/obo/DOID_74

Synonyms: Hematological disease, DISEASE OF THE BLOOD AND BLOOD-FORMING ORGANS, disease of hematopoietic system, Blood dyscrasia NOS, Blood disease, blood disorder

Definitions: An immune system disease that has_material_basis_in hematopoietic cells.

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