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65 Publications visible to you, out of a total of 65
Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: Research on prognostically relevant immunohistochemical markers in diffuse large B-cell lymphomas has mostly been performed on retrospectively collected clinical data. This is also true for … immunohistochemical classifiers that are thought to reflect the cell-of-origin subclassification of gene expression studies. In order to obtain deeper insight into the heterogeneous prognosis of diffuse large B-cell lymphomas and to validate a previously published immunohistochemical classifier, we analyzed data from a large set of cases from prospective clinical trials with long-term follow-up. DESIGN AND METHODS: We performed morphological and extensive immunohistochemical analyses in 414 cases of diffuse large B-cell lymphoma from two prospective randomized clinical trials (NHL-B1/B2, Germany). Classification into germinal center and non-germinal center subtypes of B-cell lymphoma was based on the expression pattern of CD10, BCL6, and IRF4. Multivariate analyses were performed adjusting for the factors in the International Prognostic Index. RESULTS: Analyzing 20 different epitopes on tissue microarrays, expression of HLA-DR, presence of CD23(+) follicular dendritic cell meshworks, and monotypic light chain expression emerged as International Prognostic Index-independent markers of superior overall survival. Immunoblastic morphology was found to be related to poor event-free survival. The non-germinal center subtype, according to the three-epitope classifier (CD10, BCL6, and IRF4) did not have prognostic relevance when adjusted for International Prognostic Index factors (relative risk=1.2, p=0.328 for overall survival; and relative risk=1.1, p=0.644 for event-free survival). CONCLUSIONS: The previously reported International Prognostic Index-independent prognostic value of stratification into germinal center/non-germinal center B-cell lymphoma using the expression pattern of CD10, BCL6, and IRF4 was not reproducible in our series. However, other markers and the morphological subtype appear to be of prognostic value.

Authors: H. W. Bernd, M. Ziepert, C. Thorns, W. Klapper, H. H. Wacker, M. Hummel, H. Stein, M. L. Hansmann, G. Ott, A. Rosenwald, H. K. Muller-Hermelink, T. F. Barth, P. Moller, S. B. Cogliatti, M. Pfreundschuh, N. Schmitz, L. Trumper, S. Holler, M. Loffler, A. C. Feller

Date Published: 3rd Nov 2009

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

High-dose CHOP plus etoposide (MegaCHOEP) in T-cell lymphoma: a comparative analysis of patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: T-cell lymphomas (T-NHL) generally carry a poor prognosis. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are increasingly used to treat younger patients. DESIGN … AND METHODS: We treated patients <61 years with high-risk aggressive lymphoma with four to six courses of dose-escalated CHOP plus etoposide (MegaCHOEP) necessitating repeated ASCT. Outcomes of patients with mature T-NHL (excluding anaplastic lymphoma kinase-positive anaplastic large cell lymphoma) and aggressive B-NHL were compared using multivariate Cox regression analysis. RESULTS: Compared with 84.4% of B-NHL patients, 66.7% of T-NHL patients were able to receive all treatments; the rates of progressive disease were 27.3% in T-NHL and 16.3% in B-NHL patients. At 3 years, event-free survival (EFS) and overall survival were significantly worse for T-NHL [25.9% confidence interval (CI) 10.4% to 41.4% and 44.5% CI 26.5% to 62.5%) than for B-NHL patients (60.1% CI 52.1% to 68.1%; P < 0.001 and 63.4% CI 55.4% to 71.4%; P = 0.016). In multivariate analysis, T-NHL was a strongly significant adverse risk factor for EFS (relative risk 2.2, P = 0.001). CONCLUSIONS: MegaCHOEP for T-NHL patients was no better than other high-dose regimens and was unable to address the major problems of HDT/ASCT: neither early progressions nor early relapses were reduced. This study sheds some doubt on expectations that HDT/ASCT will significantly improve outcomes for patients with T-NHL.

Authors: M. Nickelsen, M. Ziepert, S. Zeynalova, B. Glass, B. Metzner, M. Leithaeuser, H. K. Mueller-Hermelink, M. Pfreundschuh, N. Schmitz

Date Published: 3rd Jul 2009

Publication Type: Not specified

Human Diseases: T-cell leukemia

Favorable impact of the interleukin-4 receptor allelic variant I75 on the survival of diffuse large B-cell lymphoma patients demonstrated in a large prospective clinical trial.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: Recently published data indicate that host germline variations in immune genes can influence the outcome of lymphoma patients. Interleukin (IL)-4 and IL13 are crucial immune factors and may … influence the course of the disease. Both cytokines signal through the interleukin-4 receptor (IL4R). Therefore, we investigated whether polymorphisms of IL4, IL13 and IL4R genes could predict the outcome of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: In 228 DLBCL samples of the German High-Grade Non-Hodgkin's Lymphoma Study Group, the polymorphisms of IL4 (-524CT, rs2243250), IL13 (-1069CT, rs1800925) and IL4R (I75V, rs1805010; S503P, rs1805015; Q576R, rs1801275) were analyzed and the soluble interleukin-4 receptor (sIL4R) serum level was measured before the start of chemotherapy. RESULTS: Patients harboring IL4R V75 (IL4R(I75V-AG) and IL4R(I75V-GG)) had shorter overall survival (OS) (P = 0.044) and event-free survival (EFS) (P = 0.056) periods compared with I75 carriers (IL4R(I75V-AA)). Multivariate analysis adjusted to the International Prognostic Index revealed a relative risk of 1.9 for carriers of the IL4R V75 (P = 0.011) in relation to OS. DLBCL patients homozygous for the IL4R I75 and low sIL4R serum levels have the most favorable OS and EFS. CONCLUSIONS: These data support the role for host germline gene variations of immunologically important factors like the IL4R I75V gene variation to predict the survival in DLBCL patients.

Authors: N. Schoof, F. von Bonin, S. Zeynalova, M. Ziepert, W. Jung, M. Loeffler, M. Pfreundschuh, L. Trumper, D. Kube

Date Published: 12th Jun 2009

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).
GLA - German Lymphoma Alliance

Abstract (Expand)

One thousand two hundred twenty-two patients treated in the Rituximab with CHOP over age 60 years (RICOVER-60) trial were examined for central nervous system (CNS) disease developing during first-line … therapy or after a complete or partial remission had been achieved. Patients received 6 or 8 courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) administered every 2 weeks (CHOP-14) with or without rituximab. CNS prophylaxis for patients with involvement of bone marrow, testes, upper neck, or head consisted of intrathecal (i.th.) methotrexate (days 1 and 5 of first 2 courses). Fifty-eight cases of lymphoma in the CNS were observed (36/609 patients in the CHOP-14 and 22/608 patients in the arituximab-CHOP-14 [R-CHOP-14] arm). The estimated 2-year incidence of CNS disease was 6.9% (confidence interval [CI] 4.5; 9.3) after CHOP-14 and 4.1% (CI 2.3; 5.9) after R-CHOP-14. R-CHOP reduced the relative risk for CNS disease to 0.58 (95% CI 0.3; 1.0, P = .046). Cox regression analysis identified "involvement of more than 1 extranodal site" and "B-symptoms" as significant risk factors for CNS disease. Patients treated with R-CHOP-14 did not show any benefit from i.th. methotrexate. We conclude that elderly patients with aggressive CD20-positive lymphoma show a significantly lower incidence of CNS disease if treated with R-CHOP-14 instead of CHOP-14. Intrathecal methotrexate has no role in preventing CNS disease for patients treated with combined immunochemotherapy (R-CHOP-14)--with the possible exception of patients with testicular involvement.

Authors: V. Boehme, N. Schmitz, S. Zeynalova, M. Loeffler, M. Pfreundschuh

Date Published: 23rd Apr 2009

Publication Type: Not specified

Human Diseases: lymphoma

Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).
GLA - German Lymphoma Alliance

Abstract (Expand)

Recent retrospective studies of heterogeneously treated patients have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B-cell lymphoma … (DLBCL). Here, we investigated the prognostic impact of MYC aberrations analyzed by interphase fluorescence in situ hybridization in 177 patients with de novo DLBCL treated within the two prospective, randomized trials non-Hodgkin's lymphoma NHL-B1 and NHL-B2. MYC aberrations were detected in 14 DLBCL (7.9%). In a univariate analysis compared with MYC-negative DLBCL, MYC-positive cases showed a significantly shorter overall survival (OS) (P=0.047) and relevantly, though not significantly, shorter event-free survival (EFS) (P=0.062). In a Cox model adjusted for the international prognostic index, the presence of a MYC gene rearrangement was the strongest statistically independent predictor of OS (relative risk 3.4, P=0.004) and EFS (relative risk 2.5, P=0.015), and this also held true when the cell-of-origin signature detected by immunohistochemistry was included in the model.

Authors: W. Klapper, H. Stoecklein, S. Zeynalova, G. Ott, F. Kosari, A. Rosenwald, M. Loeffler, L. Trumper, M. Pfreundschuh, R. Siebert

Date Published: 30th Aug 2008

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Effect of interleukin-10 gene polymorphisms on clinical outcome of patients with aggressive non-Hodgkin's lymphoma: an exploratory study.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: Current chemotherapy can achieve high response rates in aggressive non-Hodgkin's lymphoma (NHL), but the factors that influence regression and survival remain unknown. The present exploratory … study tested the hypothesis whether interleukin-10 (IL-10) polymorphisms predict clinical outcome, leukocytopenia, or infectivity during therapy. IL-10 was chosen because immune alterations are a major risk factor for NHL, and IL-10 is a cytokine involved in inflammatory processes associated with clinical outcome. EXPERIMENTAL DESIGN: Five hundred patients with aggressive NHL treated with CHOP/CHOEP were analyzed for IL-10 gene polymorphisms, including distal loci -7400InDel, -6752AT (rs6676671), and -6208CG (rs10494879) in comparison with proximal loci -3538AT (rs1800890), -1087AG (rs1800896), and -597AC (rs1800872) according to the incidence and outcome of the lymphoma. RESULTS: No differences in allele frequencies or haplotypes were found comparing a cohort of patients with aggressive NHL/diffuse large B-cell lymphoma with a healthy control group. Patients with aggressive NHL characterized by IL-10(-7400DelDel) had shorter overall survival periods compared with the other genotypes (P = 0.004). The 3-year rate is 43.4% for IL-10(-7400DelDel) and 73.4% for IL-10(-7400InIn) and IL-10(-7400InDel) together. A significant increased risk for event-free survival is found for carriers of the genotype IL-10(-6752TT-6208CC-3538AA) (P = 0.047). Multivariate analysis of IL-10(-7400) gene variation in relation to overall survival adjusted to international prognostic index revealed a relative risk of 1.9 for carriers of IL-10(-7400DelDel) (P = 0.037). No associations were found analyzing diffuse large B-cell lymphoma patients separately. CONCLUSION: Our results indicate that IL-10 gene variations could be associated to the clinical course of aggressive NHL, which points out the importance of host factors and respective genetic elements for treatment response.

Authors: D. Kube, T. D. Hua, F. von Bonin, N. Schoof, S. Zeynalova, M. Kloss, D. Gocht, B. Potthoff, M. Tzvetkov, J. Brockmoller, M. Loffler, M. Pfreundschuh, L. Trumper

Date Published: 15th Jun 2008

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas.
GLA - German Lymphoma Alliance

Abstract (Expand)

MicroRNAs (miRNA, miR) are negative regulators of gene expression that play an important role in diverse biological processes such as development, cell growth, apoptosis and haematopoiesis, suggesting … their association with cancer. Here we analysed the expression signatures of 157 miRNAs in 58 diffuse large B-cell lymphoma (DLBCL), 46 follicular lymphoma (FL) and seven non-neoplastic lymph nodes (LN). Comparison of the possible combinations of DLBCL-, FL- and LN resulted in specific DLBCL- and FL-signatures, which include miRNAs with previously published function in haematopoiesis (MIRN150 and MIRN155) or tumour development (MIRN210, MIRN10A, MIRN17-5P and MIRN145). As compared to LN, some miRNAs are differentially regulated in both lymphoma types (MIRN155, MIRN210, MIRN106A, MIRN149 and MIRN139). Conversely, some miRNAs show lymphoma-specific aberrant expression, such as MIRN9/9*, MIRN301, MIRN338 and MIRN213 in FL and MIRN150, MIRN17-5P, MIRN145, MIRN328 and others in DLBCL. A classification tree was computed using four miRNAs (MIRN330, MIRN17-5P, MIRN106a and MIRN210) to correctly identify 98% of all 111 cases that were analysed in this study. Finally, eight miRNAs were found to correlate with event-free and overall survival in DLBCL including known tumour suppressors (MIRN21, MIRN127 and MIRN34a) and oncogenes (MIRN195 and MIRNLET7G).

Authors: A. Roehle, K. P. Hoefig, D. Repsilber, C. Thorns, M. Ziepert, K. O. Wesche, M. Thiere, M. Loeffler, W. Klapper, M. Pfreundschuh, A. Matolcsy, H. W. Bernd, L. Reiniger, H. Merz, A. C. Feller

Date Published: 10th Jun 2008

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

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