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NHL-B1

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LHA ID: 7WEYG9XWWU-4

Projects: GLA - German Lymphoma Alliance

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Marita Ziepert

Submitter

René Hänsel

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Created: 16th May 2019 at 14:00

Last updated: 16th May 2019 at 14:00

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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

Organisms: Homo sapiens

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

NHL-B1

GLA - German Lymphoma Alliance

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Marita Ziepert

No description specified

Submitter: René Hänsel

Investigation: NHL-B1

Resources: No Resources

Study type: Not specified

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Created: 7th Jun 2019 at 11:59, Last updated: 7th Jun 2019 at 11:59

Long-term ovarian function in women treated with CHOP or CHOP plus etoposide for aggressive lymphoma.

GLA - German Lymphoma Alliance

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Marita Ziepert

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BACKGROUND: Chemotherapy-associated ovarian damage comprises not only infertility, but also premature menopause. The latter has been reported as a consequence of alkylating chemotherapy for breast … cancer or Hodgkin's lymphoma. In this study, we assessed the long-term impact of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens on ovarian function in patients with aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Long-term survivors after CHOP or CHOP plus etoposide (CHOEP) treatment within the Mabthera International Trial or the NHL-B1 trial of the German NHL Study Group were requested to respond to a questionnaire and to consent to blood sampling for hormone assessment. RESULTS: A total of 46 of 81 contacted patients with a median age of 32.5 years at the time of enrolment into the aforementioned clinical trials responded to the questionnaire. The median follow-up after completion of treatment was 14 years. Last menstrual bleeding occurred significantly earlier in patients compared with the general population (47 versus 51 years, P < 0.0001). In comparison to the distribution of menopausal symptoms in the general population, the percentage of women with moderate or severe menopausal symptoms was increased. In 23 patients who agreed to participate in laboratory analyses, anti-Muller hormone as a marker of ovarian reserve was decreased when compared with correspondent age groups of the general population. CONCLUSION: Although most female patients regain fertility after CHOP-like chemotherapy, late ovarian impairment occurs frequently. Therefore, awareness of such delayed side-effects at the time of counselling is of importance.

Authors: J. Meissner, D. Tichy, V. Katzke, T. Kuhn, S. Dietrich, T. Schmitt, M. Ziepert, E. Kuhnt, T. Rixecker, M. Zorn, M. Witzens-Harig, M. Pfreundschuh, A. D. Ho

Date Published: 13th May 2015

Publication Type: Not specified

Human Diseases: lymphoma

PubMed ID: 25962442

Citation: Ann Oncol. 2015 Aug;26(8):1771-6. doi: 10.1093/annonc/mdv227. Epub 2015 May 11.

Created: 17th Apr 2019 at 13:22, Last updated: 7th Dec 2021 at 17:58

The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas.

GLA - German Lymphoma Alliance

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Marita Ziepert

Samira Zeynalova

Abstract (Expand)

To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin … Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-ECFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patients who did not (P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with ECFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study.

Authors: N. Murawski, G. Held, M. Ziepert, B. Kempf, A. Viardot, M. Hanel, M. Witzens-Harig, R. Mahlberg, C. Rube, J. Fleckenstein, C. Zwick, B. Glass, N. Schmitz, S. Zeynalova, M. Pfreundschuh

Date Published: 31st Jul 2014

Publication Type: Not specified

Human Diseases: B-cell lymphoma

PubMed ID: 24939657

Citation: Blood. 2014 Jul 31;124(5):720-8. doi: 10.1182/blood-2013-10-535021. Epub 2014 Jun 17.

Created: 17th Apr 2019 at 13:23, Last updated: 7th Dec 2021 at 17:58

Excellent outcome of young adults with aggressive non-Hodgkin lymphomas treated with CHOP-like regimens.

GLA - German Lymphoma Alliance

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Markus Löffler

Samira Zeynalova

Marita Ziepert

Abstract

Not specified

Authors: K. Hohloch, S. Zeynalova, G. Held, M. Ziepert, M. Loeffler, G. Wulf, N. Schmitz, M. Pfreundschuh, L. Trumper

Date Published: 10th Jul 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

PubMed ID: 25005242

Citation: Leukemia. 2014 Nov;28(11):2260-3. doi: 10.1038/leu.2014.213. Epub 2014 Jul 9.

Created: 17th Apr 2019 at 12:56, Last updated: 7th Dec 2021 at 17:58

Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma.

GLA - German Lymphoma Alliance

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Marita Ziepert

Abstract (Expand)

Tumors are composed of phenotypically heterogeneous cell populations. The nongenomic mechanisms underlying transitions and interactions between cell populations are largely unknown. Here, we show that … diffuse large B-cell lymphomas possess a self-organized infrastructure comprising side population (SP) and non-SP cells, where transitions between clonogenic states are modulated by exosome-mediated Wnt signaling. DNA methylation modulated SP-non-SP transitions and was correlated with the reciprocal expressions of Wnt signaling pathway agonist Wnt3a in SP cells and the antagonist secreted frizzled-related protein 4 in non-SP cells. Lymphoma SP cells exhibited autonomous clonogenicity and exported Wnt3a via exosomes to neighboring cells, thus modulating population equilibrium in the tumor.

Authors: R. Koch, M. Demant, T. Aung, N. Diering, A. Cicholas, B. Chapuy, D. Wenzel, M. Lahmann, A. Guntsch, C. Kiecke, S. Becker, T. Hupfeld, V. Venkataramani, M. Ziepert, L. Opitz, W. Klapper, L. Trumper, G. G. Wulf

Date Published: 3rd Apr 2014

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

PubMed ID: 24563408

Citation: Blood. 2014 Apr 3;123(14):2189-98. doi: 10.1182/blood-2013-08-523886. Epub 2014 Feb 21.

Created: 17th Apr 2019 at 13:10, Last updated: 7th Dec 2021 at 17:58

Parenthood in long-term survivors after CHOP with or without etoposide treatment for aggressive lymphoma.

GLA - German Lymphoma Alliance

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Marita Ziepert

Abstract

Not specified

Authors: J. Meissner, D. Tichy, S. Dietrich, T. Schmitt, M. Ziepert, E. Kuhnt, T. Rixecker, M. Witzens-Harig, M. Pfreundschuh, A. D. Ho

Date Published: 3rd Apr 2014

Publication Type: Not specified

Human Diseases: lymphoma

PubMed ID: 24689462

Citation: Br J Haematol. 2014 Aug;166(4):612-5. doi: 10.1111/bjh.12877. Epub 2014 Apr 2.

Created: 17th Apr 2019 at 13:20, Last updated: 7th Dec 2021 at 17:58

Impact of rituximab and radiotherapy on outcome of patients with aggressive B-cell lymphoma and skeletal involvement.

GLA - German Lymphoma Alliance

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Samira Zeynalova

Marita Ziepert

Abstract (Expand)

PURPOSE: To study clinical presentation, outcome, and the role of radiotherapy in patients with aggressive B-cell lymphoma and skeletal involvement treated with and without rituximab. PATIENTS AND … METHODS: Outcome of patients with skeletal involvement was analyzed in a retrospective study of nine consecutive prospective trials of the German High-Grade Non-Hodgkin lymphoma Study Group. RESULTS: Of 3,840 patients, 292 (7.6%) had skeletal involvement. In the MabThera International Trial (MInT) for young good-prognosis patients and the Rituximab With CHOP Over 60 Years (RICOVER-60) study for elderly patients, the randomized addition of rituximab improved event-free survival (EFS; hazard ratio for MInT [HRMInT] = 0.4, P > 001; hazard ratio for RICOVER-60 [HRRICOVER-60] = 0.6, P > .001) and overall survival (OS; HRMInT = 0.4, P < .001; HRRICOVER-60 = 0.7, P = .002) in patients without skeletal involvement, but failed to improve the outcome of patients with skeletal involvement (EFS: HRMInT = 1.4, P = .444; HRRICOVER-60 = 0.8, P = .449; OS: HRMInT = 0.6, P = .449; HRRICOVER-60 = 1.0, P = .935). Skeletal involvement was associated with a worse outcome after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (HREFS = 1.5, P = .048; HROS = 1.1; P = .828), but not after CHOP without rituximab (HREFS = 0.8, P = .181; HROS = 0.7, P = .083). In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a decreased risk (HREFS = 0.3, P = .001; HROS = 0.5; P = .111). CONCLUSION: Rituximab failed to improve the outcome of patients with diffuse large B-cell lymphoma with skeletal involvement, although our data suggest a beneficial effect of radiotherapy to sites of skeletal involvement. Whether radiotherapy to sites of skeletal involvement can be spared in cases with a negative positron emission tomography after immunochemotherapy should be addressed in appropriately designed prospective trials.

Authors: G. Held, S. Zeynalova, N. Murawski, M. Ziepert, B. Kempf, A. Viardot, M. Dreyling, M. Hallek, M. Witzens-Harig, J. Fleckenstein, C. Rube, C. Zwick, B. Glass, N. Schmitz, M. Pfreundschuh

Date Published: 10th Nov 2013

Publication Type: Not specified

Human Diseases: B-cell lymphoma

PubMed ID: 24062391

Citation: J Clin Oncol. 2013 Nov 10;31(32):4115-22. doi: 10.1200/JCO.2012.48.0467. Epub 2013 Sep 23.

Created: 17th Apr 2019 at 12:45, Last updated: 7th Dec 2021 at 17:58

Circulating levels of TNF receptor II are prognostic for patients with peripheral T-cell non-Hodgkin lymphoma.

GLA - German Lymphoma Alliance

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Markus Löffler

Markus Kreuz

Marita Ziepert

Abstract (Expand)

PURPOSE: Peripheral T-cell non-Hodgkin lymphomas (T-NHL) represent a small but heterogeneous and clinically aggressive subset of NHLs with a poor outcome. Cytokines or their receptors might be associated … with the clinical outcome of these lymphomas. Therefore, we tested whether gene variations and serum levels of soluble TNF receptor (TNFR)I (sTNFRI), sTNFRII, interleukin (IL)-10, or sIL-4R are predictive for treatment response in T-NHLs. EXPERIMENTAL DESIGN: Peripheral blood DNA from 117 patients with T-NHL treated in prospective clinical trials was subjected to genotyping analysis. Whenever possible, pretreatment sera were obtained, and circulating levels of sTNFRI, sTNFRII, IL-10, and sIL-4R were determined with a specific capture enzyme-linked immunoassay. RESULTS: Patients characterized by TNFRI-609GG (rs4149570) showed a trend toward better event free survival [EFS; univariate: P = 0.041; multivariate: HR, 1.76; confidence interval (CI), 0.99-3.14 with P = 0.056]. A protective role of IL-10-1087A, -824T, and -597A reported in another study was not confirmed in our cohort. Patients with circulating levels of soluble TNFRII >/=2.16 ng/mL had a 2.07-fold increased relative risk for shorter overall survival (OS; univariate: P = 0.0034; multivariate: HR, 2.07; CI, 0.92-4.70 with P = 0.081) and a 2.49-fold higher risk for shorter EFS (univariate: P = 0.00068; multivariate: HR, 2.49; CI, 1.22-5.08 with P = 0.012). Elevations of circulating levels of sTNFRI, IL-10, and sIL-4R are frequent, but the clinical response in these patients is not significantly different. CONCLUSIONS: Our findings suggest a critical role for TNF-TNFR signaling for the clinical outcome of patients with peripheral T-NHLs.

Authors: C. Heemann, M. Kreuz, I. Stoller, N. Schoof, F. von Bonin, M. Ziepert, M. Loffler, W. Jung, M. Pfreundschuh, L. Trumper, D. Kube

Date Published: 1st Jul 2012

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

PubMed ID: 22573350

Citation: Clin Cancer Res. 2012 Jul 1;18(13):3637-47. doi: 10.1158/1078-0432.CCR-11-3299. Epub 2012 May 9.

Created: 17th Apr 2019 at 12:44, Last updated: 7th Dec 2021 at 17:58

CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group.

GLA - German Lymphoma Alliance

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Samira Zeynalova

Markus Löffler

Abstract (Expand)

BACKGROUND: To describe incidence, risk factors, and influence of treatment on occurrence of central nervous system (CNS) relapse or progression in younger patients with aggressive B-cell lymphoma. … PATIENTS AND METHODS: We analyzed 2210 patients with aggressive B-cell lymphoma treated on various studies for CNS relapse/progression. Treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) +/- etoposide. Six hundred and twenty patients also received rituximab. CNS prophylaxis was intrathecal methotrexate on High-CHOEP and MegaCHOEP phase III studies if upper neck, head, bone marrow, or testes were involved. RESULTS: Fifty-six of 2196 patients (2.6%) developed CNS disease. It occurred early (median 7.0 months), median survival was 5.0 months. Patients with age-adjusted International Prognostic Index (aaIPI) 0 or 1 treated with rituximab showed a low risk for CNS disease (2-year rates: 0% or 0.5%), and rituximab decreased the risk (relative risk 0.3, 95% confidence interval 0.1-0.9, P = 0.029). Patients with aaIPI 2 or 3 showed a moderate risk (4.2%-9.7%) and no significant reduction of CNS disease with rituximab. CNS prophylaxis was of no significant benefit. CONCLUSIONS: In younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment.

Authors: N. Schmitz, S. Zeynalova, B. Glass, U. Kaiser, E. Cavallin-Stahl, M. Wolf, M. Haenel, M. Loeffler, L. Truemper, M. Pfreundschuh

Date Published: 13th Oct 2011

Publication Type: Not specified

Human Diseases: B-cell lymphoma

PubMed ID: 21989328

Citation: Ann Oncol. 2012 May;23(5):1267-73. doi: 10.1093/annonc/mdr440. Epub 2011 Oct 11.

Created: 17th Apr 2019 at 13:55, Last updated: 7th Dec 2021 at 17:58

Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group.

GLA - German Lymphoma Alliance

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Marita Ziepert

Markus Löffler

Abstract (Expand)

To evaluate outcome and prognosis of patients with T-cell lymphoma we analyzed 343 patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Two hundred eighty-nine … patients belonged to 1 of the 4 major T-cell lymphoma subtypes: anaplastic large cell lymphoma (ALCL), anaplastic large cell lymphoma kinase (ALK)-positive (n = 78); ALCL, ALK-negative (n = 113); peripheral T-cell lymphoma, unspecified (PTCLU; n = 70); and angioimmunoblastic T-cell lymphoma (AITL; n = 28). Treatment consisted of 6-8 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone) or etoposide plus (CHOEP). Three-year event-free survival (EFS) and overall survival were 75.8% and 89.8% (ALK-positive ALCL), 50.0% and 67.5% (AITL), 45.7% and 62.1% (ALK-negative ALCL), and 41.1% and 53.9% (PTCLU), respectively. The International Prognostic Index (IPI) was effective in defining risk groups with significantly different outcomes. For patients, </= 60 years with lactate dehydrogenase </= upper normal value (UNV), etoposide improved improved 3-year EFS: 75.4% versus 51.0%, P = .003. In patients > 60 years 6 courses of CHOP administered every 3 weeks remains the standard therapy. Patients with ALK-negative ALCL, PTCLU, or AITL presenting with IPI > 1 have a poor prognosis and should be considered candidates for novel treatment strategies.

Authors: N. Schmitz, L. Trumper, M. Ziepert, M. Nickelsen, A. D. Ho, B. Metzner, N. Peter, M. Loeffler, A. Rosenwald, M. Pfreundschuh

Date Published: 4th Nov 2010

Publication Type: Not specified

Human Diseases: mature T-cell and NK-cell lymphoma

PubMed ID: 20660290

Citation: Blood. 2010 Nov 4;116(18):3418-25. doi: 10.1182/blood-2010-02-270785. Epub 2010 Jul 21.

Created: 17th Apr 2019 at 13:54, Last updated: 7th Dec 2021 at 17:58

A functional polymorphism in the NAD(P)H oxidase subunit CYBA is related to gene expression, enzyme activity, and outcome in non-Hodgkin lymphoma.

GLA - German Lymphoma Alliance

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Markus Löffler

Markus Kreuz

Marita Ziepert

Abstract (Expand)

NAD(P)H oxidase is a major endogenous source of reactive oxygen species (ROS). ROS may not only be involved in carcinogenesis but also in efficacy of chemotherapeutic agents like doxorubicin. By a … comprehensive genotyping approach covering 48 genetic polymorphisms (single-nucleotide polymorphisms) in five subunits of phagocytic NAD(P)H oxidase, we asked whether they affect gene expression, enzymatic activity, and outcome of CHO(E)P chemotherapy. A highly consistent effect was observed for the CYBA 640A>G variant. In peripheral blood granulocytes of 125 healthy volunteers, the G allele of 640A>G was associated with lower NAD(P)H oxidase activity (P = 0.006). Moreover, the G allele was associated with lower mRNA and protein expression (both P = 0.02). Of clinical importance, the outcome of patients suffering from non-Hodgkin lymphoma and treated with CHO(E)P regimen was dependent on the CYBA 640A>G polymorphism. In an exploratory study (n = 401), carriers of 640GG had an event-free survival (EFS) risk ratio of 1.95 [95% confidence interval (95% CI), 1.31-2.90; P = 0.001] compared with 640AA. In a confirmatory set (n = 477), the risk ratios were 1.53 (1.04-2.25, P = 0.03). The complete set of 878 patients showed a relative risk of 1.72 (1.30-2.26) and 1.59 (1.14-2.21) for EFS and overall survival, respectively. Further molecular-biological experiments showed lower expression and reduced stability of transcripts with the G allele in lymphoblastoid cell lines. Transfection of allele-specific plasmids into HEK293 cells elicited lower activity for the G allele in a luciferase reporter gene construct. Thus, CYBA 640A>G was shown to be a functional polymorphism with possible consequences for patients receiving CHO(E)P chemotherapy and might have further implications for other ROS-mediated modalities.

Authors: M. Hoffmann, M. A. Schirmer, M. V. Tzvetkov, M. Kreuz, M. Ziepert, L. Wojnowski, D. Kube, M. Pfreundschuh, L. Trumper, M. Loeffler, J. Brockmoller